Hormones have an elegance and matchless wonder about them that is little known or understood. Part of the reason for this is that the language of hormones is so confusing with numerous acronyms and a tendency to call the same thing by many different names. The stress hormone cortisol, for example, is also referred to as hydro-cortisone, there are variants such as cortisone and corticosterone – which are essentially one and the same thing to all but very particular chemists. Not only that, but cortisol can quite correctly be called a steroid, as well as a glucocorticoid, or even a corticosteroid, depending on the context. Such confusion can make hormone-ology appear impenetrable at first, but, let me reassure you, it’s basically easy. This is not string theory or mobile phone contracts.
To start with the basics, ‘endocrine’ means secretion within, and endocrine glands do just that. They produce secretions within the gland and rely on the blood to take what they have produced to the rest of the body. Compare and contrast with the so-called exocrine glands, like digestive glands or sweat glands, which all have ducts to pipe their secretions out to the specific spot where they’re needed, like the gut or your armpit. Another (older) name for the endocrine glands is the ductless glands.
The study of hormones is called endocrinology, and someone who works with hormones is called an endocrinologist. The whole system of glands and hormones in the body is called the endocrine system. The endocrine system coordinates activity inside the body, regulates development throughout life and helps the body adapt to change outside the body. It controls things like reproduction, metabolism and growth. It can also have a profound effect on mood and emotion – which we are all too aware of. The endocrine system is one of two major communication systems in the body, the other being the nervous system. They are closely linked and indeed neuro-endocrinology, the study of hormone and nerve interactions, is one of the largest and fastest expanding areas of endocrinology.
As an illustration of the radically different speeds of the two systems, consider colour change. Watch a chameleon, octopus or squid change colour. It’s utterly dazzling, a lightning-fast moving colour display, reflecting not just the animal’s background coloration, but seemingly its mood too. If an octopus is angered this is instantly reflected in its hue. That’s the nervous system at work, for it mediates colour change in these animals. Consider a frog – its colour change system is hormone-driven. The outer layers of its skin has cells, called melanophores, containing dots of melanin pigment. If the pigment dots are clumped together, at the centre of melanophore, the animal will appear to be a light colour but if the pigment dots are dispersed throughout, the animal will seem to be a much lighter coloured creature. The dispersal of these pigment dots is under the influence of a pituitary hormone, melanocyt-stimulating hormone (MSH). Compared to the nervous system, however, it is very slow. If you put a light-coloured frog in a dark box, it will be several hours before it is well on the way to becoming a dark one. The entire light to dark process may take up to a day.
So hormones can be produced in those ductless glands, released into the blood, and have an effect on a specific tissue, far away from the gland. The upshot may be to gear things up (stimulatory) or damp them down (inhibitory). When they arrive at a cell, some change takes place in the cell, according to the message received.
Working from head to toe, the classic endocrine glands are the anterior pituitary (in the base of the brain), the thyroid and parathyroids (in the neck), the pancreas, two adrenal glands (which sit on the top of the kidneys) and two testes or ovaries. All of these glands manufacture particular hormones, some of which will be very familiar, like insulin from the pancreas and testosterone from the testes. A common feature of all these classical endocrine glands is an excellent blood supply, for blood is their main channel of communication.
The grand vizier of the hormone empire is the hypothalamus, a region of the brain which is roughly behind your eyes, and hormones are the slaves of the system, chemical messengers too small to be seen, which carry instructions to cells all over the body.
At any one time there are thousands, perhaps millions, of messages in the blood being carried by hormones. The endocrine system is one of constant change: it always strikes me as a bit like the most perfect civil service, responsive to every little nuance from every last citizen, constantly receiving messages about the state of the nation, and constantly reacting with new instructions so as to attain perfect governance and order. However, unlike real governments, where civil servants in Trade and Industry never talk to those in Health, every single department is involved and cross-linked, with each knowing what every other department is doing – and adding its own addendum to the instruction if necessary.
That grand vizier – the hypothalamus – sits at the base of the brain and is in charge of hormone production, although its ultimate master is the rest of the brain. For such an important gland, the hypothalamus is incredibly small – less than a lump of sugar.
The pea-sized pituitary (the most important of those classic glands) dangles from the hypothalamus by a little stalk. Inside the stalk is a complex network of blood vessels called the hypophyseal portal system. The hypothalamus produces two types of regulating hormone, releasing ones and inhibiting ones, all of which act on the pituitary. The portal system within the stalk carries these command hormones from the hypothalamus to the front end of the pituitary, which is called the anterior pituitary. The back end – the posterior pituitary or neurohypophysis – is more of a storage area, particularly for vasopressin, which controls water balance, and oxytocin, the hormone of love and birth, both of which are manufactured in the hypothalamus. The pituitary and hypothalamus effectively function together as one unit, known as the hypothalamic-pituitary axis.
The function of the hypothalamus is as a translation and command unit, receiving input from the brain and then sending out appropriate messages, sometimes by nerve impulses, and sometimes by employing hormones via the pituitary gland. The hypothalamus is in control because it is wired directly into its ultimate master – the brain. Everything you experience or perceive – from a bear running down the corridor at work, to a hot romance, to seeing an empty shelf where you expected food to be – the brain, via the senses, gets to know first and it has to make decisions about what to do next. The brain can parcel out response messages via the body’s two communication networks, the nervous system and the endocrine system. For an almost instant response, the nervous system is used; where a slower response will do, it’s the endocrine alternative. But there is also a third way – using nerves to stimulate the production of hormones. Three endocrine glands secrete their hormones only in response to nerve stimuli: the adrenal medulla, which pours out adrenaline and noradrenaline, the hormones that prepare you for ‘fight or flight’; the pineal gland, which secretes melatonin, hormone of sleep; and the posterior pituitary, which is the warehouse for vasopressin and oxytocin. This response is not quite as instant as that produced by the nerves alone, but nevertheless a chain reaction can occur in seconds.
How Does It All Work?
First, let me say something about terminology. The word ‘trophic’ (‘tropic’ in the US) at the end of a hormone word makes that word an adjective. The root word before it describes the target of that hormone – so ‘gonadotrophic’ means acting on the gonads; ‘neurotrophic’, acting on the nerves; ‘somatotrophic’, acting on the body and so on. The word ‘trophin’ (‘tropin’ in the US) at the end of the word makes it a noun. This means that the hormone has a releasing effect on another system – although ‘unleashing’ is a more appropriate word than ‘releasing’.
Now, let’s consider the release of thyroid hormones as an illustration of how hormones work. Hormones tend to come in pairs or groups of three. There’s the hormone itself and then there’s a mate (or two) involved in its release or inhibition. Quite often the hormone regulates itself, in that when a certain level of the hormone in the bloodstream is reached, this in itself prevents more being secreted.
The hypothalamus is bathed in circulating blood, and when blood levels of thyroid hormone are low, the hypothalamus produces thyrotrophin releasing hormone, usually known as TRH. TRH travels down the stalk connecting the hypothalamus to the pituitary, to the front section, anterior pituitary, and delivers its message: ‘More thyroid hormone needed’. The pituitary obliges, releasing thyroid stimulating hormone (TSH), which travels through the bloodstream to the thyroid gland itself, in the neck. There, in response to the message delivered by TSH, more thyroid hormone is produced.
It’s the next stage that is the key to understanding how hormones operate. The thyroid will go on producing thyroid hormones until it is told to stop. If thyroid hormones are over-produced and their levels in the bloodstream become too high, the ‘levels too high’ message is received by the hypothalamus and the amount of TRH being produced is then decreased. As a result, the anterior pituitary gets the message, ‘Slow down on thyroid production’. This is called negative feedback. If on the other hand, levels of thyroid hormone fall too low, the hypothalamus produces more thyrotrophin releasing hormone, begetting more thyroid stimulating hormone, and more thyroid hormone once again. Negative feedback systems are a very common feature of hormone function.
So we have the hypothalamus – which is part of the brain – producing releasing and inhibiting hormones in response to signals from outside the body and from signals within the body. Here are the ones you are most likely to come across.
Thyrotrophin releasing hormone (TRH) controls thyroid stimulating hormone and thence the production of thyroid hormones.
Growth hormone releasing hormone (GHRH) and its partner somatostatin which inhibit both growth hormone and thyroid stimulating hormone.
Gonadotrophin releasing hormone (GnRH) stimulates follicle stimulating hormone and luteinising hormone secretion (the hormones that control testis or ovary).
Corticotrophin releasing hormone or factor (CRH) stimulates adrenocorticotrophic hormone (ACTH), which in turn controls production of stress hormones.
These hormones act on the anterior pituitary, the front part of the pituitary gland which dangles by a stalk from underneath the hypothalamus. Four of the anterior pituitary’s hormones control specific endocrine glands. Luteinising hormone (LH) and follicle stimulating hormone (FSH) act on the gonads – that is, the ovaries or testicles. These hormones are the same in men and women, even though the target organs are clearly different. Thyroid stimulating hormone controls the thyroid gland and adrenocorticotrophin (ACTH) the adrenal glands. The anterior pituitary also produces two hormones directly: growth hormone, which has effects throughout the body, but mainly on bone and soft tissue, and prolactin, the hormone of lactation which acts on the breasts to produce milk.
Let’s look at the principal hormones produced by each of the endocrine glands.
The ovaries are the main site for the production of oestrogens, of which there are several different types. Oestrone and oestradiol are the best known. Oestrogens vary in potency – oestrone, for instance, is relatively weak, whereas oestradiol is the more potent. The ovaries also produce the hormone progesterone, which comes in a single variety and which, like the oestrogens, is a steroid hormone.
The testicles secrete testosterone. You may be surprised to know that the work of producing male hormones is shared by another pair of endocrine glands, the adrenals, although these produce far smaller quantities of male hormones. Testosterone is, like oestrogen, a steroid hormone.
The adrenals are called the fight or flight glands and are all about keeping the body going in times of stress. They are a pair of small triangular glands, one atop each kidney. The cortex, or outer portion, of the adrenal is divided into three layers, all producing steroid hormones, which, because they come from the cortex are collectively called corticosteroids. The outer layer produces aldosterone, which plays a vital role in the control of blood pressure and in the regulation of the salts potassium and sodium in the blood and tissues. Aldosterone is a mineralocorticoid (a word that describes its job of salt balance) but it is also called a corticosteroid – because it comes from the cortex. The middle layer produces cortisol, a glucocorticoid (another job word, which describes its role in regulating energy levels) and the hormone most familiar to us as the classic stress hormone. The inner, thinnest layer produces androgens – male hormones – in both men and women. Finally the inner core of the gland, the medulla, produces adrenaline and noradrenaline, which are all members of a family of chemicals called catecholamines including dopamine. These are not steroid hormones like the rest of the hormones produced by the adrenal glands, but are more similar to the hormones of the thyroid gland. Noradrenaline and dopamine have a critical role as very specific sorts of chemical messengers, which do not carry messages through the bloodstream but between one nerve cell and another.
When acting as transmitters the catecholamine carry messages across the gap between one nerve ending and the next. Neuro-transmitters are released from nerve endings in response to electrical impulses travelling down the nerve. Nerve system messaging is a bit like an electrically driven relay race, with the baton being exchanged in the gap between one nerve and the next. Adrenaline and noradrenaline are both a neurotransmitter and a hormone.
(Confusingly, Americans call adrenaline and noradrenaline, epinephrine and norepinephrine respectively. European terminology is used throughout this book but you can find the American forms in some of the references cited at the end of the book. You may also see the word ‘adrenalin’ and wonder whether it is the same as ‘adrenaline’. It is. The correct spelling is with an ‘e’ as in catecholamine.)
The thyroid is the largest endocrine organ. It sits in the neck, just below the voice box and has two lobes, one on either side of your windpipe, joined by a strap of tissue which gives it the shape of a butterfly. It produces two thyroid hormones: very large quantities of thyroxine (T4) and much smaller amounts of triiodothyronine (T3). When thyroxine reaches its target tissues it is converted to the biologically much more potent T3, so you could call T4 a pro-hormone. Unlike other hormones, thyroid hormone levels are kept remarkably constant – rather like the way the body keeps glucose levels constant. To make its hormones, the thyroid needs iodine, which it gets from food. If there is no iodine available to manufacture T4 and T3, the body will need to draw on its stores, thus keeping levels steady, no matter what the fluctuation in food supplies.
The thyroid controls metabolism and energy balance. If the body doesn’t have enough thyroid, it slows right down. If it has too much, you feel like you’re on fast-forward all the time. Although thyroxine is a hormone of metabolism in humans, it is the hormone of metamorphosis in amphibians. You can demonstrate this very easily if you happen to have a bowlful of tadpoles handy. Just put a thyroxine tablet, intended for someone who has a poorly functioning thyroid, into the water. The tadpoles will miraculously change into tiny frogs almost overnight.
There are four parathyroids, two behind either side of the thyroid in the neck. They are small – pea sized – but significant in that they regulate calcium levels. Without calcium there would be no muscle contraction or nerve transmissions and no blood clotting. The parathyroids aren’t under the direct control of the hypothalamus, but can be thought of as being an elite gland squad. They can direct how much calcium is removed from the body’s stores in the bones and how much is reabsorbed via the kidneys and intestine if blood levels of calcium fall too low. The hormone is parathyroid hormone. One further hormone closely involved in calcium balance within the body is calcitonin, another hormone of the thyroid gland.
The pancreas has two main jobs. It is a leaf-shaped organ that lies behind the stomach. About 98 per cent of it is made of tissue which secretes digestive enzymes. It is said to be an exocrine gland, because it pipes its secretions away through a duct – the pancreatic duct – into the duodenum. However, within this exocrine tissue are nests of tens of thousands of little of hormone-producing cells – the so-called islets of Langerhans. Thus 98 per cent of the pancreas is an exocrine digestive gland, but 2 per cent of it is an endocrine gland involved in regulation of the body’s fuel system.
One cell type within these islets secretes the hormone glucagon and the other sort secretes insulin. When sugar levels are high, insulin is released; when it is low, glucagon is released. These two hormones reach every part of the body and affect almost every tissue, for the body’s efficient running depends on glucose being kept within a very tight range – never too much, never too little. As constant as possible is what the body likes best.
If the islets are destroyed – as they are by the immune systems of those people who develop insulin-dependent diabetes – blood glucose levels rise astronomically. Even though the person’s blood contains huge amounts of glucose, without insulin’s help the body is unable to use it as fuel.
How is insulin controlled? Does the hypothalamus have a role in this particular scenario? There is no direct insulin regulator produced by the hypothalamus or pituitary. However, noradrenaline, cortisol, growth hormone and the thyroid hormones all play an important part in controlling blood sugar – and all of these are under the dominion of the hypothalamus.
When Is A Gland Not A Gland?
Originally the definition of a classic endocrine gland was that it secreted a hormone into the blood, which had an effect on a distant tissue. It was convenient to think of endocrine glands as being specific organs, but as more become known about hormones, it was realized that this was an over-simplification. For instance, the pancreas is a gland within a gland, because only patches of tissue within the pancreas – the islets of Langerhans – produce hormones. Although some hormone-secreting cells are collected together in glands, there are others which are just single cells found within some other organ, like the gut, liver or the skin. The hormones released from these single cells may act on themselves (so-called autocrine hormones) or they may affect nearby cells (paracrine hormones). One example is secretin, produced in the gut, another hormone which has a role in sugar regulation.
The original definition of a hormone as something which had, as its target a ‘distant organ’ proved problematic, for it became clear that hormones didn’t have to travel – they could act locally. The whole concept of what constituted a gland also became stretched. The great discovery of the last thirty years has been that far from there being just a few obvious endocrine glands, and twenty or so major hormones, many tissues act as endocrine glands in their own right, producing hormones unique to that tissue. Fat cells, for instance, are now known to produce the hormone leptin. Muscles produce IGF-2. The placenta is a hormone-producing organ. With the acceptance of this concept has come the realization that there are literally hundreds of hormones.
Many hormones are secreted either in a cyclical fashion (for instance, once a month as with female reproductive hormones) or in a pulsed way (like gonadotrophin releasing hormone, which is released in bursts, every ninety minutes or so). Hormone production varies during a twenty-four-hour period too. For example, testosterone levels are highest first thing in the morning. Growth hormone and the milk-producing hormone prolactin are released during sleep. This has implications for attempts to measure hormones. Single measurements are rarely that instructive, for they are simply snapshots at a particular moment in time. Usually urine collection over twenty-four hours will be needed to give an accurate assessment of hormone levels.
If you look at the back of medical textbooks, you will see what are called ‘reference tables’, which give the top and bottom ranges of values considered usual for levels of various body chemicals. There are also reference ranges for hormones, but what distinguishes many of them is how wide they are. There is an optimum level for good health but the important thing is that it’s what is optimum for you that counts, not what is good for someone else. We are all uniquely hormoned. Nowadays a number of organizations offer to test the levels of your hormones for ‘optimum functioning’. The usual practice is to pronounce you ‘deficient’ in some of them, before selling you what they say is required for you to reach the ‘right’ level, as defined by them. This is marketing, not science. We are not yet clever enough to know what is the best individual level of hormones for people in good health, and those that tell you they do know are to be avoided.
Receptors
All hormones have a final destination – an individual cell which the hormone has to instruct – and so another key part of the endocrine system is receptors. The surfaces of cells are covered with these receptors, which you can think of as docking bays. They are needed because most hormones can’t pass through the cell membrane, despite the fact that their message needs to be delivered to the nucleus inside the cell. They lock into ‘their’ receptor on the outside of the cell and then a strange thing happens. It’s like a celebrity walking into your local, setting off a chain of gossip inside the pub, in which one person tells another, who tells two more and so on until there’s nobody who doesn’t know that Madonna has just bought a half of lager. However, dissemination of information needs to be translated into action. It’s as if it were understood that when Madonna appears, a specific set-piece action has to take place: the landlord is informed, he phones the News of the World, who sends round a photographer so that his boozer will be on the front page. The equivalent in the cell is that of the so-called second messenger system, in which other molecules carry the news that a hormone has docked to many other molecules inside the cell, as well as telling the nucleus what needs to be done. This ripple effect means that only tiny amounts of hormone are required for a major response.
Receptors are also highly selective. They provide a specific docking bay for every hormone. Receptors are often described as being a lock and key system – only the right key will open the door. The problem with this analogy is that now more is known about receptors, it is more like hand and made-to-measure glove than lock and key. Only the right hand, slipping into the bespoke empty glove, whose fingers trail inside the cell, can fill it correctly in order to set the correct cascade of cell chemicals in motion. Another problem with the lock and key scenario is that it makes it sound as though receptors are permanent fixtures. They aren’t. There is something rather Harry Potterish about them: they can suddenly appear in huge quantities or alternatively disappear. Sometimes they can even, alarmingly, become soluble and get dissolved away before the hormone arrives. This means that a certain tissue will suddenly appear to become much more, or less, sensitive to the effects of a hormone, even though the amounts of hormone haven’t changed. If you are in a particularly grumpy mood before a period, you may not have that imbalance of hormones so popularly and irritatingly foretold, but rather more receptors than usual. Receptors are not just found on the usual suspect target organs. For instance, you’d expect oestrogen receptors in the ovary and breast, but actually oestrogen receptors are everywhere throughout the body – brain, blood vessels, bone – demonstrating the range of tissues affected by a particular hormone. Almost every week there is an announcement of the finding of a completely unexpected hormone receptor in a particular tissue. What are receptors for the hormone of starvation – leptin – doing in the testes? Or for that matter, growth hormone receptors in breast cancer cells?
There is an exception to the way docking works. Steroid hormones are, unlike the other types of hormone, fat soluble. Cell membranes are made of fat. Steroid hormones don’t need surface receptors on the membrane because, being fat soluble, they are able to just melt through the fatty cell membrane like a ghost through a wall, and then use the fatty bits inside the cell as a sort of guide rope route to dock with receptors inside the cells, usually within the nucleus itself.
What Are Hormones Made Of?
Hormones can be divided into three main types. The majority are made of protein – the smaller of these are called peptides – but there are also steroids, made from cholesterol, and finally ones derived from tyrosine which is an amino acid. Amino acids are the building blocks from which all proteins are made.
Proteins are just chains of amino acids. That’s just as in ‘just a Leonardo’ by the way. A small chain of no more than twenty amino acids is termed a peptide. Over twenty amino acids strung together are called a protein, rather than a peptide (however, this is a bit elastic). The longer the chain, the more likely the protein is to be elaborately folded and shaped. The three-dimensional shape of a protein is crucial to the way it functions. The protein hormones tend to come in tribes, like growth hormone and prolactin, which are almost identical except for a different sequence of amino acids on the end of the chain. Another tribe of big protein hormones include follicle stimulating hormone, luteinising hormone and human chorionic gonadotrophin. They are called glycoproteins, because they also have sugars attached to them. Again, they are very similar, one to another, differing only in one vital section. Although we talk of ‘growth hormone’ as if it were just one thing, in reality there are a great many natural variants in your body at the same time. It’s not known why this happens.
MODIFIED AMINO ACIDS
Another type of hormone uses a specific amino acid – in this case tyrosine – as a sort of generic low loader on to which bespoke carriages are bolted. The hormones that are based on tyrosine include the thyroid hormones and also those called catecholamines, which are produced by the innermost portion of the adrenal glands, and many of which act as neurotransmitters, facilitating messages between nerves. The catecholamines include adrenaline and also noradrenaline which is produced not only in the adrenal gland but also at nerve endings.
A third category of hormones are steroids. We tend to think of steroids as unpleasant drugs taken by bodybuilders. They are an enormously important group of natural body chemicals, which includes Vitamin D, and the bile acids, which help digestion, as well as the hormones cortisol and aldosterone, produced by the adrenals, and the sex hormones testosterone, progesterone and oestrogen. The basic building block for steroids is cholesterol and by adding different chemical groups to this molecule, completely new and very different substances can be made with, despite their similarity, radically different biological properties.
Steroid production is rather like an assembly line making a Swiss Army knife. You have the basic knife kit (cholesterol) and then various blades get added, so you can have the boy scout version with the knife and horse’s hoof cleaner, or the top of the range mountaineer special, with thirty-two blades. The point is that the mountaineer special had to be the boy scout version first – and the steroids are built on the same basis. Another analogy would be with the London Underground. If you take the Piccadilly line, always starting at King’s Cross and always finishing at Heathrow, which is the end of the line, you have to go through Holborn and Knightsbridge first. There is no bypass or short cut. It’s like that with steroids. The steroid hormone aldosterone which helps control blood pressure has to go through being the reproductive hormone progesterone and the stress hormone cortisol first. The oestrogen oestradiol is made from testosterone (a male hormone), having been oestrone (a female hormone), androstenedione (a male hormone), DHEA (a unisex hormone), and pregnenolone (a female hormone) first.
Steroids, like the tyrosine-derived hormones, seem to be considered a bit of a liability, for they are given chaperones whilst travelling in the blood, called carrier proteins or globulins. Some carriers are specific – sex hormone binding globulin (SHBG) for testosterone, for instance, or thyroid hormone binding globulin (THBG) – but others are common proteins like albumen, protein tarts who will carry anything – but only loosely bound – and definitely not in the same close heavy armlock as that of the specific binding globulins.
You might have come across the phrase ‘free testosterone’. What this means is testosterone that hasn’t got a chaperone and isn’t locked up by its carrier protein. It’s usually the amount of ‘free’ hormone that determines how well it works. Some endocrine diseases are not caused by having too much or too little of a particular hormone but by changes in the number of chaperones available which effectively either sequesters or releases more ‘free’ hormone.
What Happens When You Have Too Much or Too Little Hormone
THYROID GLAND
Diseases that are caused by too much or too little hormone are still common. For instance about 700 million people worldwide are estimated to have a goitre, an enlargement of the thyroid gland that is seen as a big lump on the front of the neck. Iodine is essential to the production of the thyroid hormones T4 and T3, but many parts of the world, particularly landlocked mountainous areas like the Alps and regions of China, have soil which is deficient in iodine. As a consequence, many people living in iodine-deficient areas have goitre. In Britain, the area around the Peak district was one such affected area and because so many people who lived there had goitre, the condition became known as Derbyshire neck. About 26 million people worldwide have brain damage caused by their thyroid condition, and of these some 6 million are sufficiently mentally handicapped that they are completely dependent on others. This condition is known as cretinism and symptoms include intellectual impairment, hearing or speech problems, stunted growth and poor movement. This misery is caused by the thyroid gland not working as it should because it is unable to obtain the iodine it needs for proper function. It is completely preventable with iodine supplements. In Britain, most of our table salt is now iodized with potassium iodide, and therefore the deficiency is no longer seen.
Thyroid problems can also be made worse by diet. An example is cassava, a staple food in Africa which, if not prepared properly, contains a chemical which blocks uptake of iodine. Soy beans also affect thyroid function, as do vegetables from the cabbage family, like cabbage itself, turnips and broccoli, further reducing what little thyroid hormone there is. The thyroid is rather like an iodine sponge. It will soak up whatever it can get hold of until it can take no more. This is why giving potassium iodide tablets to people in the immediate aftermath of a nuclear explosion will prevent their bodies from taking up radioactive iodine because the thyroid will have been so flooded by iodine that it cannot absorb any more.
Written texts make clear that in the Middle Ages the Chinese knew how to treat goitre and prescribed seaweed (which, like any food from the sea or grown by the sea, contains large quantities of iodine). In the fourteenth century, Chinese physicians recommended treating goitre with fifty desiccated pigs’ thyroids, ground up in a glass of wine. Today there is still debate as to whether or not desiccated whole thyroid extract is better than synthetic thyroid hormone.
GROWTH HORMONE
You will also be familiar with the disease caused by lack of insulin – diabetes – and with the conditions caused by too much or too little hormone – dwarfism and gigantism. Growth during the first eight to ten months of life is largely controlled by food intake, but growth hormone then becomes the dominant influence on how children grow. There are also benign balls of cells, tumours, which secrete growth hormone (GH) and this constant production of GH produces as you’d expect, very tall people – seven foot or taller – the condition is known as gigantism. If excess GH is produced after growing has stopped (again because of a tumour), a condition called acromegaly develops, which causes the bones of the hands, feet and jaw to become enlarged.
The First Book of Samuel in the Bible relates the story of David and the giant Goliath, who was said to be six cubits and a span in height. A cubit is an Egyptian measure, roughly the length of the elbow to the tip of the middle finger and reckoned to be eighteen inches. A span is half a cubit, which would make Goliath well over nine foot tall. The tallest man ever recorded was Robert Wadlow, born in Alton, Illinois, in 1918, who was 8′ 11″. He died when he was only twenty-two. Robert Wadlow had a tumour of the pituitary gland in childhood, causing an excess of growth hormone. Did Goliath have a hormone problem? I doubt it. Too much growth hormone does not make you a muscle-bound superman as we’ll see in later chapters. Quite the reverse is usually the case, with respiratory problems, diabetes and high blood pressure being the norm and disabling osteoarthritis of load-bearing joints also an early feature. By his teens, Robert Wadlow needed a walking stick.
Another common problem for those subjected to too much growth hormone is carpal tunnel syndrome, which is caused by pressure on the median nerve in the wrists, and results in numbness and loss of power in the hands. This would have made it impossible for Goliath to hold heavy items like his staff, which the Bible tells us ‘was like a weaver’s beam’, let alone his spear, of which the head alone ‘weighed six hundred shekels of iron’.
Although a very rare form of acromegaly is inherited, most cases are caused by malfunctions of the pituitary and so are ‘one offs’. A further hint on Goliath’s physique comes from the Second Book of Samuel in which it is noted that four more giants had been killed in battle by the Israelites. All are said to come from the tribe of Gath. This sounds as if the Gathites were just exceedingly tall and six cubits and a span is a myth.
However, the opposite case has been made persuasively by endocrinologist Shlomo Melmed of the Cedars Sinai Medical Center, Los Angeles. He argues that Goliath’s height was definitely the result of a pituitary tumour arising in childhood. Such tumours often press upon the optic nerve, leading to loss of peripheral vision, which might account for his seeming unawareness of David and his sling. A blow to the head for a person with this condition could have caused a massive haemorrhage, leading to death, even from a seemingly minor head injury.
The point of the story is surely that David was small by comparison and won the fight through applied weapons technology (a well-aimed sling-shot). A rather more likely sufferer from acromegaly was the Egyptian pharaoah Akhenaten, whose portraits show the typical projecting jaw of the condition.
ADRENAL GLANDS
John F. Kennedy suffered from Addison’s disease, in which the cortex of the adrenal glands atrophies, resulting in life-threatening deficiencies of cortisol and aldosterone. Up until 1940, Addison’s disease was invariably fatal, but it was then discovered that it could be treated with cortisone. Kennedy was diagnosed by a London doctor in 1947, at a time when cortisone was an extremely expensive drug: the Kennedys were said to keep quantities of the drug in safety deposit boxes around the world. Had Kennedy not been a rich man, he would not have survived, because cheaper, synthetic versions of cortisone weren’t widely available until the 1950s. As it was, he was so ill that after the diagnosis he was told that he had only a year to live and was actually given the last rites on his return sea voyage to the States.
Kennedy also suffered from serious back problems and was in so much pain that in 1954, when he was a US Senator, surgery became necessary. This can be an extremely hazardous undertaking in someone with Addison’s disease. He pulled through, but with many complications, and repeat surgery was needed. So unusual was his survival that it was written up as an anonymous case report in the Journal of the American Medical Association in 1955. No one knew that ‘37-year-old male’ was in fact John F. Kennedy until 1967, four years after his death. He also looked much healthier than he was because, ironically, another feature of Addison’s disease is a bronzing of the skin caused by abnormal synthesis of melanin pigment in the skin.
When he was standing for President in 1960, his campaign team flatly denied that he had Addison’s disease. They relied on a very narrow definition of Addison’s as a disease only caused by tuberculosis of the adrenals, to quash rumours of ill-health. Tuberculosis was about the only disease Kennedy didn’t have. Like Franklin D. Roosevelt before him, Kennedy managed to overcome debilitating health problems to become one of America’s greatest presidents.
The novelist Jane Austen, on the other hand, almost certainly did have TB-induced Addison’s disease. In an article in the British Medical Journal in July 1964, Sir Zachary Cope pointed out that Jane Austen had herself identified a key feature of the disease in a letter to her brother of 23 March 1817: ‘Recovering my looks a little, which have been bad enough, black and white and every wrong colour.’ ‘There is no disease’, wrote Sir Zachary, ‘other than Addison’s disease that could present a face that was “black and white” and at the same time give rise to the other symptoms described in her letters.’
You can do without ovaries, thyroid, pancreas – in fact most endocrine organs – provided that you receive the appropriate hormone supplements. But there is one exception. Remove both adrenal glands and you will die very quickly. There is no substitute, no way of mimicking the extraordinary second-by-second adjustments that the stress hormones of the adrenal glands make to crucial body functions. Without these glands, there is no recovery from physical or emotional trauma, no proper control of blood pressure, water balance or heart rate.
Complete loss of an endocrine gland is an extreme cause of having too little of a hormone. There are many other causes of deficiency – or excess. As we have seen, there are many steps involved in the production of a hormone, so insufficiency is not simply about not having enough of the hormone itself. Faults in any part of the chain might be the problem: in the hypothalamus, by there not being enough releasing hormone; in the pituitary, by failure of its hormones; by faulty production in the site of hormone manufacture; by poorly functioning or absent receptors or failure of the feedback systems, and so on, right down the chain.
Almost Hormones
As research has moved on, the definition of hormones has had to become rather elastic. Many of the newly discovered hormones affect cells around them, or even the cell that produced them. The discovery of other chemicals in the body has made the scientific community realize that many other molecules have jobs as chemical messengers and regulators, and that the hormone club is not quite as exclusive as originally thought. Here are three of the principal contenders for quasi-hormone status.
PROSTAGLANDINS
Amino acids are used to build the peptides and proteins of many hormones, whereas cholesterol is the building block of steroids. Another basic material is fatty acid, the major storage component of fat. Fatty acids are used to manufacture a type of strictly local hormone called a prostaglandin. The first prostaglandin that was isolated was found in semen and was thought to have been secreted by the prostate gland, hence the name. It is now known that almost all tissues produce prostaglandins, which act locally. Prostaglandins are strictly local in their action, and also have a regulatory role.
Prostaglandins get involved in all sorts of bodily reactions such as muscle contraction and inflammation, and are familiar to women in their role in period pain. The reason why aspirin works so well for period pain is because it’s an anti-prostaglandin. Prostaglandins are sometimes called ‘hormone-like’, sometimes ‘pre-hormones’, and many endocrinologists are now calling them hormones.
CYTOKINES
The endocrine system doesn’t work in isolation but in concert with other systems of the body. It has a particularly close relationship with the immune system. Cytokines are molecules secreted by immune cells that can regulate the endocrine system. There are many, many cytokines, some of whose names are familiar, like interferons, given as a treatment to those with multiple sclerosis. Another large, less familiar class of cytokines are interleukins. When you are seriously injured – a severe burn for instance – levels of stress hormones, especially cortisol and adrenaline, soar. From what you have read so far, you would think that this must be organized through the hypothalamus, which dispatches corticotrophin releasing hormone to the anterior pituitary, which then sends out adrenocorticotrophin to the adrenal cortex, which then responds by a rapid increase in stress hormones. In fact it doesn’t work like this in serious trauma because cytokines bypass the normal routes, taking messages direct to the adrenal glands themselves. In a sense, cytokines are acting in the same way as adrenocorticotrophin – even though they are not hormones.
NITRIC OXIDE
You will know nitric oxide (NO) better as a gas – it’s a major component of exhaust fumes and smog and was generally thought to be A Bad Thing – a poisonous asthma-inducing pollutant. Indeed, caution has been advised ever since Sir Humphrey Davy was nearly killed in 1800 when he decided to see what would happen when he inhaled it. Yet in the 1980s the very same molecule was discovered to be vital to the health of both body and mind – and to have a distinctly hormone-like action, as a locally produced messenger and regulator. The story of nitric acid started when it was discovered in 1867 that amyl nitrite (most familiar as the recreational drug, ‘poppers’) could relieve both high blood pressure and angina pain. Sir Arthur Conan Doyle, who was a GP in Southsea, certainly knew about it, for in the Sherlock Holmes story, ‘The Case of the Resident Patient’, written in 1893, ‘amyl of nitrite’ is mentioned as a treatment for lowering the blood pressure of a man affected by catalepsy. Its use for lowering blood pressure had been prompted by a chemist reporting flushing of his face and heart pounding during an experiment with amyl nitrite.
Something very similar had also occurred in munitions workers. The explosive nitroglycerine had been discovered in 1846. Commercial production had been pioneered by Alfred Nobel in Sweden, but it was highly unstable. He discovered how to reduce its sensitivity to shock, producing dynamite and making a fortune in the process, which he used to fund the Nobel prizes. Munitions workers handling explosives also had very low blood pressure, together with flushed hands and faces. In an extraordinary leap of faith, nitroglycerine was placed under the tongue in an attempt to provide a more long-lasting relief of pain for angina than amyl nitrite. The treatment worked and nitroglycerine is still the treatment of choice for angina pain.
For a century, no one knew why it worked so well. What links these seemingly disparate pieces of information is nitric oxide. It is released from both amyl nitrite and nitroglycerine and controls the muscle tone of blood vessel walls, dilating them and easing pain and blood pressure. This wasn’t discovered until 1987 by Salvador Moncada. It is now known that nitric oxide is an essential part of the physiology of most organs and tissues, including the brain, where it is linked to memory formation. The erection of the penis, for instance, is mediated by nitric oxide released from nerve endings close to the blood vessels of the penis – Viagra works by enhancing this effect. That is why taking amyl nitrite and Viagra is a recipe for disaster because too much nitric oxide is produced, and the result is usually a heart attack. It is a stiffy not a stiff that is required.
Nitric oxide affects secretion from several endocrine glands, including gonadotrophin releasing hormone from the hypothalamus and adrenaline from the adrenals. It regulates, it stimulates production of a hormone – and sounds pretty much like a hormone. However, it falls just beyond the scope of this book and so that is the last you will hear of this ubiquitous and intriguing molecule here.
Let me now start filling in the detail as I go on to describe the wonderful elegance of the hormonal system – as it relates to love, attraction and sex.
