In Our Time - Hormones

Episode Date: March 7, 2024

Melvyn Bragg and guests discuss some of the chemical signals coursing through our bodies throughout our lives, produced in separate areas and spreading via the bloodstream. We call these 'hormones' and we produce more than 80 of them of which the best known are arguably oestrogen, testosterone, adrenalin, insulin and cortisol. On the whole hormones operate without us being immediately conscious of them as their goal is homeostasis, maintaining the levels of everything in the body as required without us having to think about them first. Their actions are vital for our health and wellbeing and influence many different aspects of the way our bodies work.WithSadaf Farooqi Professor of Metabolism and Medicine at the University of CambridgeRebecca Reynolds Professor of Metabolic Medicine at the University of EdinburghAndAndrew Bicknell Associate Professor in the School of Biological Sciences at the University of ReadingProduced by Victoria BrignellReading list:Rachel Carson, Silent Spring (first published 1962; Penguin Classics, 2000)Stephen Nussey and Saffron Whitehead, Endocrinology: An Integrated Approach (BIOS Scientific Publishers; 2001)Aylinr Y. Yilmaz, Comprehensive Introduction to Endocrinology for Novices (Independently published, 2023)

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Podcasts This is in our time from BBC Radio 4 and this is one of more than a thousand episodes you can find on BBC Sounds and on our website. If you scroll down the page for this edition, you can find a reading list to go with it. I hope you enjoy the programme. Hello, at any moment of the day, throughout our lives, our bodies are producing chemical signals

that are sent to other parts of the body. We call these chemicals hormones, and we produce more than 80 of them, of which the best known are arguably estrogen, testosterone, adrenaline, insulin and cortisol. On the whole, we don't notice hormones as their goal is homeostasis, keeping the levels of everything in the body as they are meant to be. But their actions are vital for our health and well-being and influence many different aspects of the way our bodies work. With me to discuss hormones are Andrew Bicknell,

Associate Professor in the School of Biological Sciences at the University of Reading. Rebecca Reynolds, Professor of Metabolic Medicine at the University of Edinburgh, and Siddharuki, Professor of Metabolism and Medicine at the University of Cambridge. Saddaf, what are hormones? So hormones are effectively proteins, which are made by one particular gland in the body, and then circulate in the bloodstream to go and act at another different site. And effectively, they coordinate all of our physiology, and they allow us to do very fundamental things, such as metabolise the physical,

food we eat to grow and to reproduce. And our hormones even control our immune system. Is there any way to explain to the list of what a hormone looks like? I mean, they have slightly different shapes, but they are sort of often proteins, so small molecules, but they go and they act on receptors. So they effectively dock onto receptors. And then that process of docking onto a receptor triggers a chain reaction, which then regulates the switching on of genes or the sending of signals inside a cell. So if you imagine almost like a bit of a spacecraft or something travelling around a highway and then docking in at a certain position.

The receptors take many different shapes and sizes, but they're often very particular to receive the signal from a specific hormone. And they're really shaped so that the hormone can fit precisely into the receptor and then when it does so, it triggers a response in that particular cell in the body. How are they produced? And in one particular part of the body are they produced? So the hormones are produced by many different endocrine gulfs. glands. So it's a gland that knows how to make hormones, basically package them up into small

packets and then release them on cue into the bloodstream. So you, for example, the thorough gland or the ovary or the testis. But also those particular cells that have the machinery to make the hormones are also found in our gut and actually even in our fat cells. So there are a lot of different cells in parts of the body that have the capabilities to make hormones. They make many different hormones. So you always have the same set of genes within a cell, but a particular cell will have a certain function, and that means that it switches on or it makes or produces a particular hormone. And that fits with its overall function.

So the thyroid gland mainly focuses on making thyroid hormones. You don't tend to make them in the ovary, for example. So you have a specific recipe, if you like, for making the hormones that are then released into the bloodstream. All species have effectively hormones or hormone-like molecules. So flies have them, worms. have them, mice have them, all kinds of animal species have these hormones. And they play very fundamental signals because you've always needed to have a system

to coordinate your behaviour and your physiology. And that's essentially what our hormones do. The more and more I do this program over the last many years, there seems to be a factory inside all of us, a very skillful, advanced, developed, fine, crafty factory. Very much so. And I think that's exactly what our hormones are actually the conductors of an orchestra. They're effectively the system that pulls everything together and makes sure that everything is acting in concert and at the right time.

Thank you. Andrew Bicknell. How does the body know when to release hormones? So in your introduction, you mentioned this idea of homeostasis, this idea that we sort of stay the same. So much of the endocrine system is regulated by the fact that something changes and it needs to be corrected. So to give you an example, when we eat something,

our food goes into our stomachs and then into our guts where we absorb the nutrients and the levels of glucose will rise in our blood. And that rise in that level of glucose needs to be sensed or is sensed and we release insulin into our circulation,

into our blood. That travels around the body and it binds to its specific receptors which encourage the cells to take up that glucose and store it, and it gets taken up into fat, into the liver and into muscle. So by doing so, the glucose level will then begin to lower, and it returns back to where its set point is. So most hormones are produced in response to something changing and returns that, whatever that level is back to where it should come from.

I'm fascinated by these receptors. I mean, they're just lying there waiting for something to happen, and then they can grab it and use it. Yeah, that's exactly it. And this is the wonderful thing I think about the endocrine system in itself. The gland, the endocrine gland releases the hormone into the blood, and that travels all the way around the body. And every cell and tissue will see that hormone, but it only acts on a few of those tissues,

or it might act on many of them. And the way that it does that is because the cells that respond to the hormone, effectively they express, they produce the receptor that the hormone binds to. So I think a really good analogy to that might be the idea if you think of the hormone as a key and you're walking down a street and there's all these doors with locks in it and all of a sudden you keep trying the key in all the locks until you find the one that it fits and the door opens.

It's extraordinary, isn't it? It is amazing. Do you have any idea when this developed and how it developed? The early part of the endocrine, hormones per se, the first molecules are more like steroid molecules rather than the peptides and proteins that were mentioned earlier. there are examples of these even in bacteria, but not in the same sort of light.

They're sort of signalling molecules, which again sense things in the environment and cause of response. Rebecca Reynolds, what's the signipings of the pituitary gland and the hypothalamus? Yeah, so the pituitary gland and the hypothalamus are really the key regulators

and the key controllers, if you like, of the way the hormone system works. In fact, we call the pituitary gland the conductor of the endocrine or. because it's really there got a vital critical role in coordinating. So the hypothalamus is a small part of the brain, and what it does is it receives signals from various parts of the brain, from the nervous system, from other tissues,

and then it integrates those signals and then sends signals to the pituitary gland in the form of releasing hormones or inhibitory hormones. And this then tells the pituitary to produce other hormones. The petulatory's got two parts. The anterior part of the pituitary produces these steward. stimulating hormones which then go out in the bloodstream to all the different glands that we've just been talking about to make those individual glands release their hormones. And the back part of the pituitary actually releases stored parts of chemicals that the hypothalamus has made, which regulate our salt and water balance.

So it's a bit like a thermostat running a central heating system in the way that they talk to each other. So if we think of the hormones circulating around in the body as like the room temperature, If they go up too high, then the signals from the pituitary and the hypothalamus will get switched down, like the thermostat, and then vice versa. If the temperature goes down or the hormones go down, then the pituitary and the hypothalamus will switch up to make more hormones be produced. Do you know, you've talked about them in the brain. Do you know where they're situated in the brain and why they're situated and where they're situated? So the hypothalamus is in what we call the higher centres of the brain, below an area of the brain that we call the thalamus. and then it's anatomically located just above the pituitary gland

which is a pea-sized gland that's really almost just behind the back of your nose at the very base of the brain. And they think they're some tiny to do all this business. Very small, but they're packed full of lots of different cells which can release these different signals. Do they link in with other systems in the body? Absolutely. So the hormone system or the endocrine system is really tightly linked in with almost all our...

different systems in the body, particularly with our metabolism, with our reproductive system, with our nervous system and our immune system. And I guess we see this most when one of the hormones goes wrong. So for example, if you develop an overactive thyroid and you're producing too much thyroid hormone, you have symptoms in virtually all parts of your body. So your metabolism goes into overdrive, you feel really hungry, you eat a lot, but you lose weight. Your nervous system get stimulated so you feel really shaky, your heart races too fast, you can't sleep at night, and then your temperature regulation goes out of kilter, so you feel very, very hot. And then we see the opposite of that thyroid gland is underactive, so you've become very tired and sluggish,

you gain weight, you feel really cold. And so you can see that even though it's just one hormone that's gone wrong, it's affecting lots of different parts of the body and lots of different systems. But then central control moves in and corrects that. So that's what tries to happen, but in disdemean. then sometimes the system is so switched on or switched off that the central control cannot manage to overcome those changes. What strikes me is how efficient it seems to be? I guess it's regulated a second by second or a minute by minute system and so some hormones take a little bit longer to regulate whereas others can be changed very quickly and it's extremely

intricate. The regulation of the hormone system is very conserved between species so you'll have a very similar response in a different setting or a different animal, but the actual underlying mechanism will be very similar. Thank you. So now it's a huge system and it's time to look at some of it. Let's talk about food, which most people know about. Can you tell us how hormones impact on the intake of food, etc? Yes, well we've learnt really quite a lot about this in the last 20 years. So it's quite a recent understanding that we have. And what we now know is that that actually how much we eat, what we eat, and how rewarding or how much we crave food is strongly influenced by our hormones. And so those hormones come from our fat, for example. So we

used to think that our fat tissue was just there to store extra calories. But actually our fat can make hormones. One of them is called leptin. We also make hormones from our gut, and they're released directly with relation to meals. So when you eat a meal, depending upon where the food goes in the gut, certain hormones are released, and they tell the brain about how full you are, and that sends a signal to end your meal, or to end eating. So there's a... What if you

are you able to ignore this? So of course we can all recognise that sometimes we can override those signals. But it does explain why some people feel more full, more easily than others, and other people can override it more easily. So yes, we can override it

on a sort of, at a single attempt, but over time, generally speaking, those hormones will influence how much you tend to eat. And what's interesting is those hormones work in the brain. So that's where they send the signals from the gut, the fat, the liver, those other organs, back to the brain. And the brain then has to put it all together. Now, the brain circuits in the brain respond to those hormones, but they're the same circuits that are influenced by our environment. So if you read a nice menu, or you go through a recipe, or you see some advertising, what we don't realize is that the

those signals are taken into the brain and they act on those same circuits that our hormones are acting on. And that's partly how you can override that feeling of fullness if you happen to see a menu describing a very nice piece of cake at the end of your meal. Because you're actually got a part of the brain that's overriding some of those fullness signals. So it's not automatically and mechanistic. So there is an automatic element, but you can sometimes override it. Now, what's tended to happen is because we can sometimes override it, we've tended to think that we can always override it and it's under our personal control. And actually, that's something fundamental that we now understand is not true. It's a bit like breathing. We breathe most of the time automatically without thinking

about it. But occasionally, if I ask you to, you can hold your breath for a certain amount of time. You can voluntarily override the system. But most of the time, you'll do what the system dictates you to do. Thank you. Andrew, you get more and more fascinating, isn't it? It is. What affects the length of time that hormones stay in the body? Okay, so the different, there's different types of hormones, so we've talked a little bit about protein hormones and a little bit about steroid hormones, and there's really three main types. There's these protein

hormones, the steroid hormones, and there's also another one known as a modified amino acid, which are three main types. And they do have different lengths of time. that they exist in the body. So the protein hormones and the variant of the protein hormones, which we call peptide hormones, which are like very small proteins, they tend to be in the body for quite a short length of time. So what we call their half-life,

so the time for half of it to disappear from the blood. And those are measured in often in minutes to hours, where some of the other molecules, the steroid molecules, they have much longer lives in the body, which often can be from hours to days, for example. And the way that this is regulated is the way that, we actually get rid of our hormones. So the peptide and protein hormones are mainly broken down by the kidneys and by the liver.

The steroid hormones are mainly broken down by the liver. And often steroids, for example, they're bound up with other molecules that circulate them, help them circulate in the body. And by doing so, that makes them last longer. So the peptide hormones, they tend to act very fast. So they have a very quick mode of action and then they disappeared. Where those steroid hormones, their action tends to last much. much longer, okay, because they hang around for much, much longer.

What are they made of? So the protein and the peptide hormones, they're made of things called amino acids, which are the building blocks of proteins. And essentially, we have genes which encode them, and there's a sequence of those amino acids. We have 20 naturally occurring amino acids that we find in proteins that make all of our proteins up. And the arrangement of those, the order of those,

gives the hormone molecule its properties and also its shape. The steroid molecules, on the other hand, they're made all made from cholesterol. We often hear that cholesterol is bad for us and we shouldn't eat too much cholesterol, but it actually forms the precursor to these molecules and all of the steroid molecules, things like testosterone and progesterone, and estrogen and cortisol and so on,

are all made from cholesterol. And they've got quite a common structure to them, but with some little modifications on the side of them. And the other family of hormones, these modified amino acids and the thyroid hormones is probably one of the best examples of those and also adrenaline is another example of a modified amino acid.

This is where we take one of those amino acids and it's chemically changed and it has a bit stuck on it to change its biological properties. And we have one particular amino acid called tyrosine, which is the one that's most often changed to make these amino acid hormones.

Rebecca, what are some of the significant differences that various hormones make during pregnancy and child? birth, for instance? So in pregnancy in childbirth, the mother undergoes huge hormonal changes. There's some really complex

interactions between both the mother and the baby and also the placenta which signals the different hormones between. We see classically as pregnancy progresses that many hormones rise in very dramatic levels, so things like insulin, cortisol,

estrogen, progesterone, they all rise during pregnancy. And the reason they're doing that is they're partly preparing the mother for the pregnancy, so laying down of food supplies, so storage of fat, and then subsequent release of those nutrients to the baby, so that the baby grows, and then also preparing the mother's body for the changes that happened during childbirth. And we know that these hormones are also really important in terms of the growth and development of the baby. So for example, cortisol, which is a major stress hormone, that's really

important for the baby's growth, but also important for the ways that various tissues and organs will mature. But the mother has these really high levels, and it's really important that the baby doesn't have too much of the hormone, because otherwise it might actually cause problems. So the placenta has a series of systems, which means it acts like a gatekeeper to prevent the mother's hormones going over to the baby. And it actually has an enzyme within the placenta that breaks down the active hormone and turns it into an inactive byproduct so it protects the baby.

So this system is exquisitely regulated to ensure that the babies receive the correct amount of hormones which will then impact on their growth and development. Why do you think that sort of exquisite regulation comes from? I think because one of the reasons, if I may, why I think it's a fine art

is that actually because just small variations make things go wrong. So you have to have a lot of of controls to get it just right. So essentially, as we were talking a little bit about before, if you have too much or too little of some of these hormones, you get very fundamental problems. If it's the thorough hormone, it happens very early, the brain doesn't develop. Children will have learning difficulties, they won't be able to walk. You get some very fundamental problems. So to avoid easily tripping over into too much or too little, you need to have a very

fine system to control everything and keep it stable. And so I think, what we've developed is essentially proteins that will carry and protect those hormones, as Andrew was describing. You've got proteins that will reduce it if it's a little bit too much, that will change the level depending upon your age or your puberty or pregnancy. So you need a fine-tuned system to keep everything. Basically, it's like a Ferrari. You have to keep everything in sync. I keep being fascinated by how this occurred, this exorview system.

So it will be an evolutionarily phenomenon. Some of the hormones that we've talked about, as I said, so leptin, the one that's made by fat, flies have an equivalent hormone telling a fly how much fat it has on board and if it has enough nutrients to survive. So you have something very fundamental for survival. So even a regular fly has that.

So people have it, but then people have to have extra levels of control. So these things have evolved, over time. And actually some of this we're only now discovering because we have better tools to measure the hormones and the other chemicals in the body that regulate them. So it came together slowly but you've been discovering

rather slowly too. Well I think collectively we've discovered quite a few I think. What's fascinating though now is that we are actually still finding there's a lot that we didn't know. Because of technological advances we can now measure very low levels of hormones

and we can measure the gene and we can actually measure them in every single cell in the body. That's something that we and others are doing right now. So we're opening up some of those closed doors and we're finding that actually there's an awful lot more that hormones can do and there are hormones that we didn't know about. Why is free will in all this? So it really returns to the point that actually, of course,

there is an element of free will, but many of the processes that we've talked about occur spontaneously and subconsciously. What do you mean by subconscious in this context? So, for example, we haven't talked yet about the flight fright response. So we're coming to that. So that's a very fundamental response, right? You see something scary and you will feel fear and anxiety and you will immediately get an adrenaline rush and you will get a faster heart rate. Your blood pressure will go up. You'll feel a bit sweaty. But that's so

quick. That's not you saying, oh my goodness, I've seen something scary. I better get ready to run. It happens automatically the second you see something. So these things happen automatically before your conscious mind has time to tell you to do something. How does your conscious mind know that what's coming towards you is threatening? So you receive these signals and they go into parts of the brain like the amygdala, for example. So the amygdala will respond pretty immediately if you show somebody like a scary face or if you show somebody snarling, for example, a photograph in a second, you'll get a detector signal in your amygdala indicating fear.

And that response to fear then communicates to the high. hypothalamus, which then sends a signal to the adrenal gland to release your hormones, your stress hormones. So it's a very, very fast electrical signal that then gets transmitted through these circuits leading to the release of these hormones. Can I carry on with you about free will, Andrew? Why does free will figure? I mean, it's all happening because I see something that goes click and then it goes another click and another click and another click. It's nothing to do with me. No, well, we've evolved. These are very primitive research.

responses and we have a whole system set up in us to effectively come back to this idea of homeostasis in a way of all these things that the whole system is just kept running and kept in check without us knowing anything's happening our blood pressure is regulated the amount of glucose we have in our blood is regulated exquisitely without us even knowing about it and in a way you know I guess that allows our free will to be thinking of other things ultimately I think the The bottom line is we're not as in control of things as we like to think we are. And that happens for all kinds of things. So we think we're going to control how perhaps we may be able to control some elements of our behaviour at certain times.

You might choose not to eat that extra slice of cake, even if you're getting a signal in your brain telling you that it's rewarding. But if you constantly get that signal, it gets quite hard to override it voluntarily. So just because we can sometimes override doesn't mean we're. are always overriding. A lot of the time the system is just running. Can I just add something on to this? I think one of the things that I find fascinating about the system

is that these molecules, these, essentially these peptide protein hormones and cholesterol, the mechanisms by which our bodies produce more, different organisms produce them, is being completely conserved. You know, every organism, the way that, for example, peptide hormones are made, these small proteins,

the way that they're made, the way that their genes encode those amino acid sequences and the way that those molecules that they make, the proteins are then produced and processed into these smaller peptides is the same in worms and flies as it is in us. So the same machinery. It's exactly the same machinery. And that is amazing, I think, which really shows you that this is a fundamental necessity for life, for successful life. Rebecca, throughout our lives, the levels of some hormones come and go. What bearing does it have on the discussion? So I think this is, I think probably one of the really good examples of hormones that come and go through our lives are the sex steroids, so estrogens and testosterone.

We see a really good example when we go through puberty, when we get big surges of these hormones. They're needed, therefore, to help us go through puberty, so that transition from childhood to adulthood, the changes that happen in our bodies when that happens. But then also with puberty and adolescents, then hormones get a bit of bad press because they're also so. with things like mood swings, with greasy skin, with development of spots. And then we see the same hormones, again, towards particularly in women, when they go through the menopause, women's estrogen levels fall off dramatically. And that then leads to a whole load of new different symptoms, so things like hot flushes, and then the risk of bones becoming thin and risk of heart disease. So I think stereotomans have such huge variation. Actually, they have less variation in men.

they tend to be a bit more constant, although even in men they have what we call a circadian rhythm, so they're higher in the morning and then lower at the rest at the end of the day. Do you know where that is? Why that is? Again, that's controlled by the hypothalamus. There's lots of different complicated mechanisms by which these signals are varied, and we have these things called clock genes, which regulate the way that different hormones and other peptides and proteins in the body

are released at different times of the day. So can we go back to fight and flight, which is easy for me to cotton onto? Can you develop that a bit? Yes, so the flight-flight response is a very fundamental response. It's really about escaping from a dangerous situation or from a predator. How do you detect it? Do you smell it? Do you see it? All kinds of things. So you may see it, you may smell it, you may hear it, you may touch something. So absolutely any peripheral sensory signal can then send ultimately a signal to the hypothalamus,

which is that control centre that we talked about. And it has a direct link to what we call the autonomic nervous system, which is sympathetic and a parasympathetic limbs. Effectively, you can think of them as the accelerator and the brake. And so the accelerator is a sympathetic system, which basically turbocharges you to run away from this scary signal by releasing adrenaline. And it makes your heartbeat faster, your blood pressure,

you breathe more quickly, you start to sweat, and that's your accelerator kicking in. You have a break, a natural break, to oppose that, and that's the parasympathetic system. And then after the scary signal has gone or died down or you've run away from it, that will sort of ease in and slow everything down. Now, we have this, and all animals have this,

it's very fundamental. And there's another sort of layer that comes in. If the stress continues, you would then bring on board cortisol as another hormone that gets released to help you deal with this frightening situation. How does it help? So it helps by basically maintaining that sympathetic system, but it also starts to kick in

and release energy so that you have enough energy reserves to deal with the situation. So it might make you want to eat more. It releases some of your nutrients so that you have enough energy for your muscles to run, for example. So we have a very strong setup to deal with flight or fright. And then what happens in the real world now, of course, is quite challenging, is that commonly people will trigger that response for things which may not be quite so threatening. So for example, it may be perfectly reasonable to have that response if you're being threatened by an intruder.

But getting that response because you're angry in a traffic jam is probably not necessary. But invariably, it's a physiological response to getting angry in the traffic jam. And what happens is if we trigger that response relatively easily, we're in a situation that's not that threatening, that's when we perceive anxiety. Why? Because it's the same thing. So basically you release all of those hormones

and that hormones give you the feeling of a fast heart rate, breathing more quickly, feeling anxious. You feel aroused, you feel alert on edge. So that is a symptom that is perfectly reasonable if you're going to run away from a threat. But if you're sitting in a traffic jam or you're stressed at home because of the family situation, then you perceive that as anxiety.

Thank you very much. Andrew, is it possible to synthesize hormones for medicinal uses? Yeah, absolutely. We've been using hormones as medicine for many, many years. The first molecules were artificially synthesized, really, in the 1930s, which were some of the steroid hormones, which was one of the first things that were made in the lab. Probably some of the first therapeutic protein hormone we used was insulin in the early 20s, mid-20s. What happened there is that, The Canadians Banting and Best discovered the insulin molecule, and they realised that you could treat people with type 1 diabetes. In those case, they had no source for a lab source of insulin, but they realised that you could extract it from animal tissue, so, for example, from a pig pancreas,

and it works perfectly well in humans. And this is one of the things we mentioned earlier about how conserved, what we call conserved, the idea that these hormones are very, very similar. And we, you know, some of the first therapy that was, that was used was from these purified purified hormones from animals. In later years

there's been some of the hormones are very species specific so they're only working humans for example and one of those is growth hormone and the first people who suffered from or the first treatment of people who suffered from a lack of growth hormone really started in the late 1950s and we had to purify it from

in that case from human peturatories and there were some health problems that came along with that with unfortunately that although these these preps might have been free from bacteria and viruses, they contained what was known then as slow viruses, which some people might have heard of Kreuzv-Yakob disease, or CJD and the mad cow BSE, which is the underlying protein that causes those conditions. And some of these preps actually had those, those in them, these proteins, which unfortunately some of the people that were treated with those hormones actually developed CJD a little bit later life.

So what's then happened is that we've started producing some of these hormones in bacteria. So we could take the gene that encodes the protein sequence and we put them into bacteria and they will produce the protein molecule, which we can then take from the bacteria and use them to treat us. So things like, for example, growth hormone and insulin, for example, are all produced in bacteria now. So they're all synthetic and they're obviously free from all those problems that used to happen. Yes. What opinion do you have, Rebecca? on this synthetic hormones?

Well, we use these hormones for treating endocrine problems, so hormone problems. Hormones to treat hormones? Hormones to treat hormones. Oh yes, hormones to treat hormones that are lacking or missing. So when we're missing a hormone, sometimes that's a life-threatening condition. So, for example, Andrew was just talking about type 1 diabetes.

If people don't have insulin, then they're not able to survive. And so we can treat diabetes now with insulin. Another example would be people who don't make enough of stress hormones and then we have to give them back synthetic stress hormones which they need to take for the rest of their lives and also they need to modify the doses if they're unwell for example. And then sometimes we use synthetic hormones to treat people who've just got symptoms but it's not life-threatening.

So an example would be giving women hormone replacement therapy if they've got very bad symptoms of the menopause or giving men testosterone therapy if they've got low testosterone and have symptoms of erectile dysfunction or decrease libido. And then we also use these synthetic hormones in examples where we're treating other conditions. So, for example, synthetic steroid hormones are very powerful at reducing inflammation. So we can use those and treat people who have autoimmune diseases or who have inflammatory conditions.

So those would be some examples. Do you have anything about that? Yeah, no, I think, and I think you came to a nice point there with other many, other conditions and it's because the hormones control so much of our system that we can harness that power to treat many different conditions. So asthma and many other disorders, arthritis, can be treated because we can understand how the hormones regulate the inflammation or the immune system and then fine-tune that response. What more would you like to know at this time in order to make your investigation more perfect? I think there are many, many conditions for which many

conditions, many diseases that people suffer from, for which we have an incomplete understanding. And, you know, anybody who looks after people will know that there are many conditions for which we don't quite understand why something happens. And that's because we have an incomplete understanding of how our hormones work on many different organs of the body at the same time. So we've talked about the classical ones and the things that we know, but there's an awful lot of things that we don't know, for example. So that people... What do we not know? So what we don't really know is we only know things if there's a big effect. What we don't know is what is the added contribution of lots of little effects around the body.

So for example, if we talked about steroids, as synthetic hormones that we might use to treat somebody with asthma, we've learnt when we treat people for a long period of time that can have a bad effect on their bones, it can have an effect on their skin, on their hair. But there are probably quite a few other effects those treatments may be having, for example on their mood, on their brain and other organs of the body, that we just simply can't measure or quantify. So it would be great if we had more sensitive tools

to be able to understand, to measure hormone levels at a really small level and then to figure out what hormones are doing precisely in every cell and every tissue and put that knowledge together to get an integrated map. Is that possible? Is that by a... Yeah, it's coming. It's coming. I think what we're finding is that technological, advances in many different fields are allowing us to understand some of that very, very detail.

What we now need to do is basically scientists, doctors and others across disciplines, need to put their heads together and build a more connected map. We tend to figure out one area at a time, but fundamentally to understand how hormones work, you have to link it together. And that's really, I think, what the challenge is now. What would the benefits be? I think the benefits can be huge, firstly for our scientific understanding, but particularly for many other problems that we're yet to be able to solve or to treat.

So I am very excited about the potential that actually we're now moving into an era where we should have a much greater and more detailed understanding of how hormones work. And with that, I hope, an ability to treat many conditions and maybe even prevent some conditions because we know how they emerge. Andrew, there are chemicals in the environment which come into play here. Can you tell us about them? Yeah, so it was appreciated many, many years ago, really back nearly to the birth of endocrinology as a discipline that you could, there were chemicals or there were factors in the environment which could affect our endocrine system. And back in the 1920s, it was realised that animals that were fed, perhaps mouldy feed stuff, would start to have reproductive issues.

And it turns out that there are many, many chemicals, both natural and more predominantly man-money, which can interfere with our endocrine system. They essentially act like the natural hormones. They bind to the same receptors, and they cause all sorts of problems. A lot of reproductive issues, for example, is one of them. Things, for example, with fish in rivers, for example, that were downstream as sewage works.

They start to become female rather than male because of the steroids that are in the sewage. Some of those are coming from oral contraceptive pills. for example. There's been problems with alligators as well, having the same problems in America. And the gators are a problem from... Well, they essentially become feminized. They become female. What happens when they become female? Well, they can't reproduce. But there's been many, many chemicals in the environment

which have been linked to all sorts of issues by effectively interfering with our endocrine system. And to be honest with you, we don't really know the long-term effects of that. We've got a long way to go on that. Rebecca. There's also quite a lot of interest in these so-called endocrine disruptors in pregnancy. We can find evidence that there's microparticles, microplastics in the placenta, in the cord blood, even getting into the baby. We don't really know what they're doing. There's a lot of what we call association studies. So people have recorded how much microplastics people have been exposed to and then looked at pregnancy outcomes. But we still don't know whether it's a causal pathway yet.

The microplastics is a whole new field which is really, I think, quite worrying, actually because we're finding them turning up in places all over our bodies, in our brains. I don't think we really fully understand the effects of all the chemicals that we are exposed to every day in the environment, which we have no choice but to be exposed to. They come through our water, through our food, through what we breathe. And I say this has all really come about since the beginning of the industrial age. And it is quite hard. And I think, you know, the reason that you were a little cautious about,

estimating the scale of the problem is that because we don't know yet the scale of the problem because we haven't been able to measure it. So it's very hard to pinpoint. You gave some examples that we can pinpoint, but there's probably quite a few things where it's hard to measure that this particular chemical in that food or exposure in the environment caused this particular problem. But there's already several examples that we can prove. And so the potential is really that we need to really quite rapidly understand how these things work.

but one of the major ways they're going to be doing these different things is by mimicking the effect of the natural hormones that we have in the body. So why do you think, is there the next big move, Rebecca, about hormones? So I guess it would be, I think probably in the next few years, we will see big advances in the way that we can treat hormone problems and the way that hormones can be better tailored to individuals. I think what we've been talking about, what we've really highlighted is that the,

endocrine system or the hormone system is very, very tightly regulated and very, very complex. And so therefore, our current treatments that we use go quite a long way from mimicking that. We know that we're starting to get a little bit better. So we do have some drugs, for example, that can now be modified in the way that they're released so that we can have higher levels in the morning and lower levels in the evening to more closely mimic what goes on in humans. But we've also maybe got other ways where technologies can also help. And for us, example, artificial intelligence and machine learning. We've come a long way with the delivery of insulin,

which used to be delivered through big syringes intermittently throughout the day, rather than responding to the day minute by minute or second by second fluctuations in the body. So we can now have very clever glucose sensors which talk to the insulin pump via an algorithm, meaning that levels of insulin can be really varied second to second. So I think that's probably a way that will develop

with other systems going forward. And as we were talking about earlier with more detailed tools that we have, so more ability to do genomics, then hopefully we'll be able to much more personalise these treatments and really tailor them for the individual in a precise way. Yeah, I mean, I think I'm very excited about learning more about how these hormones are working in every single cell

in every single tissue in the body and how it all comes together. I mean, that's a big question. But I think we are making some pretty big advances. In the next few years, I think we will really take a big step forward in our understanding in those areas. And why we like to take us to? And I think that will take us to a better understanding for treatment, but also for prevention of conditions and diseases. And we'll start to learn about it will give us a framework on which we can then build the other things that we've talked about.

So part of the challenge of understanding how chemicals and the environment affect health is that we've got too many unknowns. If you have a framework for understanding exactly how the hormones work together in every cell, then you can start to test that and say, okay, how does a particular chemical in the environment affect multiple things? You can actually directly test that. So I think these kinds of advances will occur in fairly large steps now, driven by technological changes. And finally, Andrew? Yeah, I'd agree. Technology drives science. It always has done. And this idea, as scientists, we tend to be very focused on our individual pet love, our own little system.

And it's very easy to forget that it exists in a much bigger system. And I think the idea of trying to pull all the things together and understand all the different subtleties and how they actually work as a team essentially is really where the future lies. And this comes back and coming back to the endocrine disruptors. The idea that, again, most of the studies that have been done on that are on individuals, chemicals, but of course we're exposed to a sea of these things, and it's then how do they all work together, what do they do as a group? And really, the only way to understand that is to really understand how the endocrine system itself works as a group and as a team. Well, thank you all very much. Thank you, Sadaaf Fuluki, Rebecca Reynolds and Andrew Bicknell and our studio engineer Emma Hart. Next week, we'll be going down the rabbit hole with Lewis Carroll for Alice's Adventures in Wonderland.

Thanks for listening. And the In Our Time podcast gets some extra time now with a few minutes of bonus material from Melvin and his guests. A different topic indeed. Well, thank you very much for that. I'm afraid there's more work for you to do if you do, my. Quite a lot, I think. What didn't you have time to say that you'd like to have discussed?

We didn't really talk about childhood. Okay, so a lot of different, you know, hormones affect hugely a lot of critical things to do with early development, childhood, how our brains work. There are, you know, conditions like autism, conditions that are hyperactivity. There are a lot of conditions which people wouldn't necessarily associate with hormones, which are reflecting changes in the chemicals in the brain, which work like hormones. Maybe that's a bit too far away. but these are kind of common things that people will have heard about and know that. Why don't we know as much about that as you would like to? Again, it's been hard to measure and because it's hard to understand in detail what happens within the brain.

But we are now beginning to realize that actually in the same way that we have hormones that go round the body and send signals to multiple different big organs, we have small hormones or signals like neuropeptide, small ones that travel within the brain and actually communicate. changes within the brain. And so you can effectively have a hormone that affects your mood. It can affect your levels of agitation or aggression. It can keep you calm. So quite a lot of subtle aspects of our behaviour that we've tended to think again, maybe under voluntary control, are strongly influenced by our hormones. You mentioned actually about teenagers and mood swings in relation to the menstrual cycle, in relation to pregnancy. Of course, there are many

effects, but people anecdotally know about hormones and mood, but actually there's a whole area of behaviour that is modified by our hormones. Rebecca, you were being pointed out then. Yeah, I mean, I guess that one of the things that we also know that we didn't really talk about is the way that hormones can influence the development of the baby during pregnancy, but then that can then have lifelong effects on the way that it grows and develops, so it can signal its risk of getting diabetes in later life and getting high blood pressure and getting cardiovascular disease. We don't really understand exactly how that works, but it's certainly set up

in pregnancy when the baby's still in the womb. I had potentially thought about talking about when we were talking about synthetic hormones and the use of synthetic hormones that we are actually doing a current trial that is funded by the NIHR where we're looking at whether these synthetic steroid hormones might have benefits for women who have twin pregnancies. So whilst we know that steroid hormones have lots of different effects, there's still categories where we have actually very limited understanding, and that's why we're trying to do this very large multi-centre, randomised, controlled trial, inviting pregnant women with twin pregnancies to take either the synthetic hormone

or to take a placebo, so a dummy type of treatment, and then to follow up the children to see the impact that it has on the twins. and whether they need to go to the neonatal unit, which can sometimes be a complication of twin pregnancy. Yeah, I guess one sort of area that we didn't really talk about, we talked a bit about hormones and food, and also the sensation of fullness and driving appetite is, of course, this new generation of medications

for the treatment of obesity and for weight loss, which are receiving a lot of attention. They work by effectively acting on those hormone receptors. So the reason that those medications work is they're effectively telling the brain that you're full. and you therefore want to eat less and therefore you lose weight. So essentially those medications are harnessing

the hormone system that we have. How do they work on the receptors? So they basically, they dock onto those same receptors. So they basically mimic the hormone and they dock onto the receptor and they trigger fullness response. So you feel full, you don't want to eat so much, you often don't even desire appetizing food that much.

And that's why then people lose weight. So it's an example of how treatments can harness the hormone system to effectively treat conditions such as obesity and diabetes. And they have really dramatic effects on weight loss as well. So people will lose significant amounts of weight. But interestingly, as soon as they stop taking the treatment, the weight goes back on. Which makes complete sense from what we were talking about at the very beginning because it's a homeostasis system.

It's a hormone system. So you perturb in one direction, the body will trigger a set of responses to restore, you to an even keel. It depends what even is. It depends what even is. And so that relates to this concept which we didn't quite name, but you alluded to a little bit, Andrew, was of set point. So at the beginning, we talked about homeostasis, which is keeping what even is, is balance. And we generally have a very precise set point for certain things, like temperature.

So if you get too hot, you will sweat. If you get too cold, you will shiver. And you're doing these things to restore your set point to normal. we do actually have a set point for weight, which then is surprising how come everybody's not a perfect weight. Well, actually, probably in reality, we have like a set point range. And different people have a different set point naturally, and that's influenced by our genes.

And one thing that we didn't talk about is actually our genes will strongly influence all of our hormones. And so the level of a particular hormone you may have is not a single number, it's often a range. and where you lie in that range will be influenced by many things, but one of the big things is your genes. So some people who are naturally more likely to be heavy will naturally have a higher set point for their weight. Whereas there are other people who can eat what they like and they stay slim, they naturally have a lower set point. And the same will actually happen for quite a few different other hormone systems in the body.

I think the point is, is coming back to weight, there's an evolutionary advantage. If you're, if, you know, we're used to eating every day, you know, regular meals and so on. But, of course, you know, in nature, that's not really the case. Yeah, you might actually have to, you know, you have a meal, you kill something or whatever it might be, and you eat as much as you can. And then you'll go for a period of not eating at all because while you're trying to find the next meal, you know. And, of course, we're evolved, yeah. It's an evolutionary advantage to us to manage to eat as much of that in one go as you can

because you don't know when the next meal's coming. And, you know, that persists with us now. And it's useful to be able to store extra calories. And it's useful to be able to store it, yes. Where, you know, perhaps if you don't do it, it's not such an advantage. See, when you don't know where your next meal's coming from. Well, thank you all very much. That really was fascinating.

Thank you very much indeed. Thank you. It's good. We came back to set point in her mistakes. Yeah, it's fine. Would anyone like a tea or coffee? Melvin, do you want tea? I like a cup of tea, yes, please.

Cup of tea, please. I'd love a cup of tea. Yep. It's fine, thank you. Thank you so much. With a big whiskey and it will be good. The Post Office Horizon scandal has shocked Britain. Post Office IT scandal, which has had so much publicity, hasn't it, over the life?

This is a scandal of historic proportions. I've been following the story for more than a decade, hearing about the suffering of sub-postmasters like Joe Hamilton and Alan Bates. It was just horrendous. The whole thing was horrendous. I was told you can't afford to take on post office. And about their extraordinary fight for justice. What was motivating you?

Well, it was wrong what they did. Listen to the true story firsthand from the people who lived it in the great post office trial from BBC Radio 4 with me, Nick Wallace. Subscribe on BBC Sounds.