Hormones and Endocrinology

1. Hormones and Endocrinology The endocrine glands, by producing and releasing hormones, play a critical role in homeostasis. By definition, endocrine glands are organs or tissues that produce chemical signals released into the bloodstream and effect target cells that may be located anywhere in the body. The definition distinguishes endocrine function from the chemical signaling that occurs between neurons; that chemical is not released into the bloodstream, but only into the cleft between nerve cells.

2. Some endocrine glands release their hormone(s) into the circulatory system at the gland itself. Others (labeled neurosecretory cells in fig. 26.1B) release their hormone(s) at some distance from the cell body of the hormone producing cell. However, they are still released into the circulatory system. There are a variety of chemicals that act as hormones: 1. short chains of amino acids called peptides, or longer ones that are proteins 2. amines (e.g. thyroxin, derived from the amino acid tyrosine) 3. steroids (derived from cholesterol)

3. There are only two ways hormones communicate their signals to target cells: A. Peptide, protein, and amine hormones communicate using a “second messenger” system. The process: 1. Circulating hormone binds to cell surface receptors on the target cell membrane. 2. Binding causes a conformation change that affects “second messenger” molecules (protein kinases or phosphatases). 3. Through a chain of reactions the cellular response is activated.

4. B. Steroid hormones are lipid soluble, and can pass through the cell membrane. They bind to an intracellular receptor and act inside the nucleus of target cells. The receptor-hormone complex binds directly to DNA at very specific sites, activating the transcription of specific genes, and leading to the production of specific protein(s).

5. There are a very large number of hormones produced by glands that occur throughout the head and torso of your body. We can’t cover all of them, but here’s where they are produced:

6. The hypothalamus and the pituitary The so-called “master gland” is the hypothalamus. It produces two peptide hormones that are released from neurosecretory cells that extend into the posterior portion of the pituitary. It also releases ‘releasing factors’ that stimulate the anterior pituitary to release its hormones.

7. The posterior pituitary hormones are: Oxytocin – this hormone causes contraction of target muscle cells. At the end of pregnancy, it causes contraction of muscle cells in the uterine wall that are the key to birth of the fetus (parturition). Later, it causes muscle cells surrounding milk glands in the breasts to contract, leading to milk ejection.

8. ADH (or antidiuretic hormone) – promotes the retention (reabsorption) of water from the filtrate in the distal tubules and collecting ducts of nephrons in the kidney. It is part of the control system to maintain the osmolarity of the blood.

9. The releasing factors (individually) stimulate the release of hormones from the anterior pituitary.

10. The hormones produced by the pituitary are all proteins. Some of the hormones are basically involved in metabolic responses: TSH – thyroid stimulating hormone – causes the thyroid to accelerate production of T3 and T4 (triiodothyronine and tetraiodothyronine). Note that this, like the other anterior pituitary hormones, has as its target another endocrine organ. Also, that this hormone is released by a hypothalamic stimulus – TRF – thryroid stimulating hormone releasing factor.

11. When the feedback system that adjusts the releasing factor in response to circulating T3 and T4 levels, problems arise: If feedback does not slow or shut off TRF, too much thyroid hormone ends up in circulation. The result, called Graves’ disease, more frequently caused by an autoimmune problem, has apparent symptoms: weight loss, excessive sweating, bulging eyes (exopthalmos).

12. Insufficient thyroxin causes the release of more TRF, and in turn more TSH. In adults, the thyroid grows (hypertrophy) and the apparent symptom is a goiter Adult hypothyroidism can readily be treated with oral thyroxine. Childhood hypothyroidism is more serious. Developmental effects include stunted growth and mental retardation (the medical term is cretinism). It, too, if detected early, can be treated with oral thyroxine.

13. GH or growth hormone – its release is stimulated by another releasing factor from the hypothalamus – GRF (growth hormone releasing factor). Growth hormone has a very broad spectrum of effects and targets: 1) amino acid uptake and protein synthesis are stimulated; 2) long bone extension (height growth) is stimulated indirectly, by stimulating the release of growth factors from the liver. Overproduction leads to giantism – height, but also pronounced brow ridges and other effects. Underproduction leads to pituitary dwarfism – all parts in proportion but small.

14. ACTH or adrenocorticotrophic hormone – again controlled by a hypothalamic releasing factor, stimulates hormone-producing cells in the adrenal cortex to release steroid hormones called collectively corticosteroids. One group are called mineralocorticoids. They affect salt and water balance, some by affects on kidney reabsorption. The other group are called glucocorticoids. They affect the conversion of glycogen (stored starch) to glucose, as well as (when necessary) breaking down muscle proteins to make glucose. They are also anti-inflammatory.

15. Other hormones are not directly metabolic in their end effects: Prolactin – under the control of hypothalamic hormones. This hormone has different affects on different animal groups. In us, it stimulates milk production by milk glands in the mammary. In fish, it is involved in blood osmolarity and its regulation. In amphibians, it regulates development during the tadpole stage. In birds, it is important in fat metabolism and regulation of reproductive physiology.

16. Hormones affecting the testes or the ovaries: FSH and LH – both hormones are produced by the anterior pituitary in both sexes. Effects clearly differ. In males: FSH stimulates production and maturation of sperm cells; LH stimulates secretion of sex hormones (mainly testosterone) from interstitial cells in the testes. In females: FSH stimulates the growth of a follicle and the maturation of an egg; LH promotes the secretion of estrogen, then the maintenance of a corpus luteum and its production of progesterone.

17. Endorphins, sometimes called ‘natural morphine’, are also released by the anterior pituitary (and by other parts of the brain). They seem to mainly affect pain receptors, but their function(s) are still somewhat hazy. Remember, thus far we’ve considered only the anterior pituitary, though also mentioning some of the hormones released by trophic hormones (those stimulating other endocrine cells to secrete hormones). Now for those other hormones…

18. Many hormones are regulated more directly, by sensing blood chemistry directly. That is the case for the hormones regulating blood calcium ion (Ca++). Two opponent hormones increase blood calcium when it drops below a set point (parathyroid hormone from the parathyroid glands) and calcitonin from the thyroid gland. There are four parathyroid glands, two on the surface of each of the paired thyroid glands. Their hormone causes increased calcium re-absorption in the kidneys, increased calcium uptake in the gut, and release of calcium from the bones. Calcitonin has opposite effects.

20. Control of the amount of glucose in circulation is managed by two opponent hormones made by two kinds of islet cells in the pancreas. When blood sugar increases above the homeostatic level (90mg/100ml blood), insulin is released by β cells of the islets of Langerhans. Insulin causes cells to take up more glucose from blood, and causes the liver to take up sugar and store it as glycogen. When blood sugar decreases below the level, different islet cells,  cells, release glucagon, which has opposite effects – the liver breaks stored glycogen down and releases glucose.

22. The disease resulting from inadequate regulation of blood sugar is well known – Diabetes mellitus. There are two forms of the disease: 1) Failure of islet cells to produce any or sufficient insulin. This is insulin-dependent or type I diabetes. Insulin is protein that cannot be taken orally; it would be digested. Control is by insulin injection. 2) Failure to respond sufficiently to circulating insulin (to take up enough sugar). This form is typically adult onset (age > 40). It is treated by some combination of diet, exercise, and drugs (glucose spargers, uptake/pancreatic stimulators)

23. The opposite problem can also occur – hypoglycemia or low blood sugar. It can occur due to over-responsive β cells that produce too much insulin after a meal, or it can occur as a result of treatment for diabetes (insulin injection or stimulation of production). The symptoms are sweating, nervousness (even the shakes) and weakness. If blood sugar remains too low, convulsions and diabetic coma can occur, and can lead to death. In one famous case (movie: Reversal of Fortune), Claus von Bulow injected his wife Sonny with sufficient insulin to drive her into an irreversible diabetic coma.

24. Stress responses: the adrenal medulla The adrenal medulla releases stress hormones when stimulated by nerve signals (not hormones) from the hypothalamus. The hormones (amines chemically) are epinephrine and norepinephrine. These hormones are part of the “flight-or-fight” response. They cause: 1) glycogen breakdown and increased blood glucose 2) increased blood pressure 3) increased ventilation rate 4) increased metabolic rate 5) altered circulation (< to digestive system)