The Endocrine System at a Glance (II)

Some general comments about the book can be found in my first post about it. I don’t have a lot of other things to add, but I do want to cover some more stuff from the book. Below some observations from the chapters about human reproduction, as well as some stuff on energy homeostasis.

…

“The ovum and sperm pronuclei fuse to form the zygote, which […] has the normal diploid chromosomal number […]. The zygote divides mitotically as it travels along the uterine tube, and at about 3 days after fertilization enters the uterus, when it is now a morula. The cells of the morula continue to divide to form a hollow sphere, the early blastocyst, consisting of a single layer of trophoblast cells and the embryoblast, an inner core of cells which will form the embryo. The trophoblast, after implantation, will form the vascular interface with the maternal circulation. After around 2 days in the uterus, the blastocyst is accepted by the endometrial epithelium under the influence of estrogens, progesterone and other endometrial factors. This embedding or implantation process triggers the ‘decidual response’, involving an expansion of a space, the decidua, to accommodate the embryo as it grows. The invasive trophoblast proliferates into a protoplasmic cell mass called a syncitiotrophoblast, which will eventually form the uteroplacental circulation. By about 10 days, the embryo is completely embedded in the endometrium.
If the ovum is fertilized and becomes implanted, the corpus luteum does not regress, but continues to secrete progesterone, and within 10–12 days after ovulation the syncitiotrophoblast begins to secrete human chorionic gonadotrophin (hCG) into the intervillous space. Most pregnancy tests are based on the detection of hCG, which takes over the role of luteinizing hormone (LH) and stimulates the production of progesterone, 17-hydroxyprogesterone and estradiol by the corpus luteum. Plasma levels of hCG reach a peak between the ninth and fourteenth week of pregnancy, when luteal function begins to fade, and by 20 weeks, both luteal function and plasma hCG have declined.
The syncitiotrophoblast secretes another hormone, human placental lactogen (hPL) […]. Its function may be to inhibit maternal growth hormone production, and it has several metabolic effects, notably glucose-sparing and lipolytic, possibly through its anti-insulin effects. […] The corpus luteum synthesizes relaxin, which relaxes the uterine muscle […] Progesterone concentrations rise progressively during pregnancy, and a major function of the hormone is thought to be its action, together with relaxin, to inhibit uterine motility, partly by decreasing its sensitivity to oxytocin […] A[n] important role of estrogens is to stimulate the steady rise in maternal plasma prolactin. Prolactin […] is the postpartum lactogenic hormone […] The placenta, which takes over the production of the hormones of pregnancy from the corpus luteum, is part of what is termed the fetoplacental unit. The placenta attains its mature structure by the end of the first trimester of pregnancy. […] The placenta is not only an endocrine organ, but also provides nutrients for the developing fetus and removes its waste products. […] The placenta lacks 17-hydroxylase and therefore cannot produce androgens. This is done by the fetal adrenal glands, and the androgens thus formed are the precursors of the estrogens. The placenta converts maternal and fetal dehydroepiandrosterone sulphate (DHEA-S) to testosterone and androstenedione, which are aromatized to estrone and estradiol. Another enzyme lacking in the placenta is 16-hydroxylase, so the placenta cannot directly form estriol and needs DHEA-S as substrate.”

“Normal fertility in the male is produced by a complex interaction between genetic, autocrine, paracrine and endocrine function. The endocrine control of reproductive function in the male depends upon an intact hypothalamo–pituitary– testicular axis. The testis has a dual role – the production of spermatozoa and the synthesis and secretion of testosterone needed for the development and maintenance of secondary sexual characteristics and essential for maintaining spermatogenesis. These functions in turn depend upon the pituitary gonadotrophin hormones: luteinizing hormone (LH; required to stimulate testicular Leydig cells to produce testosterone); and follicle stimulating hormone (FSH; required for the development of the immature testis and a possible role in adult spermatogenesis). Gonadotrophin production occurs in response to stimulation by hypothalamic GnRH. Testosterone exerts a negative feedback on the secretion of LH and FSH and the hormone inhibin-β, also synthesized by the testis, has a specific regulatory role for FSH.”

(A thought which occurred to me while reading these sections of the book: ‘It is fortunate that living organisms do not need to understand in detail how their reproductive systems work in order to have offspring…’)

“The term ‘functional disorders’ is used to describe a group of conditions [disorders of reproductive function in females] in which there are no structural or endocrine synthetic abnormalities in the pituitary–ovarian axis. Hypothalamic amenorrhoea is usually associated with weight-reducing diets, often with excess exercise […] It is the commonest cause of secondary amenorrhoea seen in endocrine clinics. Although a reduction in weight to 10% below ideal body weight is usually associated with amenorrhoea, there is wide variation between women. Changes in body composition, particularly reduced fat mass, are crucial to the characteristic hypothalamic changes of impaired GnRH secretion, loss of gonadotrophin pulsatility and subsequent hypogonadotrophic hypogonadism […]. The treatment of weight- and exercise-related amenorrhoea is specifically weight gain and reduction in exercise. […] Untreated, hypothalamic amenorrhoea is associated with reduced bone mineral density and ultimately osteoporosis. Women with long-term hypoestrogenaemia should have their bone density recorded and, if there is significant osteopaenia or osteoporosis, combined estrogen/progesterone replacement therapy should be considered.”

“In birds and mammals, testosterone sexually differentiates the fetal brain. The fetal brain contains androgen and estrogen receptors, which mediate these actions of testosterone. […] there is evidence that testosterone causes changes in the fetal brain during sexual differentiation of the brain at about 6 weeks.”

“The precise nature of the influence of testosterone on behaviour is unknown, due in part to the limitations of methods of study. In humans, there is no apparent relationship between plasma levels of testosterone and sexual or aggressive behaviour. It seems that behaviour has a powerful influence on testosterone production, since stress drives it down, as does depression and threatening behaviour from others. In captive primate colonies, subordinate males have raised prolactin and very much reduced plasma levels of testosterone.”

“About 120 million sperm are produced each day by the young adult human testis. Most are stored in the vas deferens and the ampulla of the vas deferens, where they can remain and retain their fertility for at least 1 month. While stored, they are inactive due to several inhibitory factors, and are activated once in the uterus. In the female reproductive tract, sperm remain alive for 1 or 2 days at most.”

…

“Blood pressure is raised (i) when the heart beats more powerfully (positive inotropic effect); (ii) when arterioles constrict, increasing the peripheral resistance; (iii) when fluid and salts are retained; and (iv) through the influence of cardiovascular control centres in the brain, or a combination of two or more of these factors.”

…

“In recent years, adipose tissue has become recognized as a highly metabolically active organ. [For one example of a publication going into much more detail about these things, specifically in the context of cancer, see incidentally Kolonin et al.] […] The neuroendocrine system plays a critical role in energy metabolism and homeostasis and is implicated in the control of feeding behaviour […and for much more about this, see Redline and Berger’s book.] […]. Fats are the main energy stores in the body. Fats provide the most efficient means of storing energy in terms of kJ/g, and the body can store seemingly unlimited amounts of fat […]. Carbohydrate constitutes <1% of energy stores, and tissues such as the brain are absolutely dependent on a constant supply of glucose, which must be supplied in the diet or by gluconeogenesis. Proteins contain about 20% of the body’s energy stores, but since proteins have a structural and functional role, their integrity is defended, except in fasting, and these stores are therefore not readily available. Circulating glucose can be considered as a glucose pool […], which is in a dynamic state of equilibrium, balancing the inflow and outflow of glucose. The sources of inflow are the diet (carbohydrates) and hepatic glycogenolysis. The outflows are to the tissues, for glycogen synthesis, for energy use, or, if plasma concentrations reach a sufficient level, into the urine. This level is not usually reached in normal, healthy people. […] Regulation of the glucose flows is through the action of endocrine hormones, these being epinephrine, growth hormone, insulin, glucagon, glucocorticoids and thyroxine. Insulin is the only hormone with a hypoglycaemic action, whereas all the others are hyperglycaemic, since they stimulate glycogenolysis. […] Integration of fat, carbohydrate and protein metabolism is essential for the effective control of the glucose pool. Two other pools are drawn upon for this, these being the free fatty acid (FFA) pool and the amino acid (AA) pool […] The FFA pool comprises the balance between dietary FFA absorbed from the GIT [gastrointestinal tract], FFA released from adipose tissue after lipolysis, and FFA entering the metabolic process. Insulin drives FFA into storage as lipids, while glucagon, growth hormone and epinephrine stimulate lipolysis [breakdown of fats]. The AA pool in the bloodstream comprises the balance between protein synthesis and the entry of amino acids into the gluconeogenic pathways.”

“In humans, food intake is determined by a number of factors, including the peripheral balance between usage and storage of energy, and by the brain, which through its appetite and satiety centres can trigger and terminate feeding behaviour […]. Leptin is secreted by human adipocytes but it may be more important (in the human) in the long-term maintenance of adequate energy stores during periods of energy deficit, rather than as a short-term satiety hormone. Feeding behaviour in humans can be initiated and sustained not only through hunger, but also through an awareness of the availability of especially palatable foods and by emotional states; the central mechanisms underlying this behaviour are poorly understood.”