Hormone

• 1. Introduction

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  In 1849, a German physiologist named Arnold Adolph Berthold castrated a group of roosters and watched something strange happen. Their wattles and combs shrank. Their crow grew weak. They lost their aggression and their attraction to females. Berthold suspected the testes held the answer, so he did something unexpected. He took a single testis and placed it loose inside a rooster's abdominal cavity, far from where it belonged. The bird behaved normally anyway. From that result came a radical idea. Some chemical, secreted from the organ, was traveling through the body to do its work. The location did not matter. The chemistry did. That chemical would later be identified as testosterone, but the broader category had no name yet. What exactly is a substance that speaks across the body without a wire to carry the message? How does a molecule released in one organ change the behavior of a cell it never touches? And why do plants, fungi, and animals all rely on the same trick to run their lives?

• 2. The Chemical Messenger

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  Ernest Starling gave the phenomenon its name in 1905. He took the word hormone from the Greek meaning to arouse or excite, and defined it as the chemical messengers which speeding from cell to cell along the blood stream, may coordinate the activities and growth of different parts of the body. The definition is functional, not structural. A hormone is identified by what it does, sending a signal to distant organs or tissues, rather than by what it is made of. That broad definition lets wildly different molecules share the label. Gases such as ethylene and nitric oxide qualify. So do steroids like oestrogen, amino acid derivatives like epinephrine, and proteins like insulin. Eicosanoids such as prostaglandins and thromboxanes belong as well. The unifying feature is reach, not shape. A hormone produced in one place exerts its effect far from where it was made. Multicellular life leans on this constantly. In vertebrates, hormones govern digestion, metabolism, respiration, sleep, excretion, lactation, growth, reproduction, and even mood. In plants, they shape nearly everything from germination to senescence. The next puzzle is how a molecule drifting through the blood manages to change one specific cell and leave the rest alone.

• 3. How The Signal Lands

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  A hormone affects a distant cell by binding to a specific receptor protein, and the cell's chemistry decides which door it can use. Water-soluble hormones, such as peptides and amines, cannot easily slip through the membrane. They act on the surface, triggering second messengers like cyclic AMP inside the cell. Most peptide and many eicosanoid hormones bind to G protein-coupled receptors, a class of seven alpha helix proteins threaded through the membrane. Lipid-soluble hormones take the opposite route. Steroids, derived from cholesterol and built from four fused rings, pass straight through the plasma membrane. They reach receptors in the cytoplasm or nucleus, members of the nuclear receptor family of ligand-activated transcription factors. Once bound, the hormone-receptor complex crosses into the nucleus and attaches to specific DNA sequences. There it regulates which genes are expressed, raising the levels of the proteins those genes encode. The rules have exceptions worth noting. Brassinosteroids, a sixth class of plant hormone, are lipid soluble yet still attach to their receptor at the cell surface. Some steroid receptors, too, turn out to sit on the plasma membrane rather than inside. The same hormone can also reach several cell types in different tissues, each responding in its own way. Insulin is the classic case, triggering a diverse range of systemic effects across the body.

• 4. The Logic Of Restraint

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  High blood sugar sets off a chain that demonstrates how the body keeps its own chemistry in check. A rising serum glucose concentration promotes insulin synthesis. Insulin then lowers glucose and restores homeostasis, and as the effect takes hold, insulin levels fall again. This is negative feedback, and it governs the rate of hormone biosynthesis and secretion throughout the body. The trigger is subtle. Higher hormone concentration alone does not switch off production. The feedback must be set off by overproduction of an effect of the hormone, not merely its presence. Several forces can stimulate or inhibit secretion. Other hormones do it, as do plasma concentrations of ions and nutrients, the activity of neurons, and environmental changes in light or temperature. One group, the tropic hormones, exists mainly to command other glands. Thyroid-stimulating hormone, for example, drives the growth and activity of the thyroid, which then raises its own output of thyroid hormones. The body also prepares for speed. Cells store biologically inactive prohormones that can be converted quickly into active form when a stimulus demands it. Eicosanoids work on a tighter leash still, acting only on nearby target cells and degrading rapidly so they never reach distant sites.

• 5. Discoveries In Plants And Pancreas

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  Charles Darwin, famous for evolution, spent the 1870s watching plants bend toward light alongside his son Francis. They found that light is perceived at the tip of a young stem, the coleoptile, while the bending happens lower down. The pair proposed a transmissible substance carrying the direction of light from tip to stem. Other plant biologists dismissed the idea at first. Decades later it was vindicated. In the 1920s the Dutch scientist Frits Warmolt Went and the Russian scientist Nikolai Cholodny, working independently, showed that an uneven buildup of a growth hormone caused the bending. In 1933 Kögl, Haagen-Smit and Erxleben isolated the hormone and named it auxin. Animal physiology saw its own breakthroughs around the same era. British physician George Oliver and physiologist Edward Albert Schäfer, of University College London, studied adrenal extracts and published their findings in two reports in 1894. The adrenaline in their extract was the first hormone to be discovered. In 1902 William Bayliss and Ernest Starling cut the nerves to an animal's pancreas to test whether the nervous system controlled its secretions. It did not. A factor released from the intestines into the bloodstream was stimulating the pancreas, and they named it secretin. Plants, notably, never evolved specialized glands. Auxin is produced mainly at the tips of young leaves and in the shoot apical meristem, and the main site of production can shift across a plant's life depending on its age and environment.

• 6. Hormones Versus Nerves

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  Neural signals can race along nerve tracts at speeds up to 100 meters per second, and that velocity marks the sharpest line between two systems often confused for each other. A neurotransmitter typically acts across micrometer-scale distances and delivers its message in milliseconds. A hormone works on a far larger spatial and temporal scale, and its signals can travel virtually anywhere the circulatory system reaches, taking seconds, minutes, or even hours. The two also differ in character. Neural signaling is all-or-nothing, a digital action. Hormonal signaling is continuously variable, scaling with hormone concentration. There is a hybrid in between. Neurohormones are produced by neuroendocrine cells that receive input from neurons, combining endocrine reflexes with neural reflexes. In this pathway an electrical signal from a neuron ends in the release of a chemical, the neurohormone, which then enters the bloodstream to reach its target just as a classic hormone would. Behavior and hormones also feed each other. Hormone concentration does not by itself incite behavior, since that would override external stimuli, but it raises the probability of an event. Behavior and environment in turn shift hormone levels, forming a loop where each side keeps adjusting the other.

• 7. Hormones As Medicine

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  Estrogens and progestogens rank among the most commonly prescribed hormones, used for hormonal contraception and hormone replacement therapy. The therapeutic catalogue runs wide. Thyroxine, given as levothyroxine, treats hypothyroidism, and a thyroxine-binding protein carries up to 80% of all thyroxine in the body, a crucial element in regulating the metabolic rate. Steroids treat autoimmune diseases and several respiratory disorders, and many diabetics rely on insulin. Otolaryngology preparations often contain pharmacologic equivalents of adrenaline, while steroid and vitamin D creams are used widely in dermatology. Dose changes everything. A pharmacologic or supraphysiological dose means an amount far greater than a healthy body naturally produces. The effects can differ from natural responses and may be useful, though not without potential side effects. Pharmacologic doses of glucocorticoids, for instance, can suppress inflammation. Regulation cuts the other way too. Hormones are ligands, molecules that signal by binding to a receptor site. A competing ligand called an antagonist can occupy that site and block the hormone from binding, leaving the target cell unable to respond. That blocking principle, turning a receptor into a switch that can be held open or shut, is where much of hormone-based medicine begins.