Gerald Litwack

Estrogens and Progestins

The endocrine physiology in the female and the interplay of the many hormones associated with sex determination, conception, fetal development, birth, growth, puberty, the reproductive years (lactation), and finally the menopause beautifully illustrate the complexity and responsivity of this highly differentiated endocrine system. The gonadotropins—follicle-stimulating hormone and luteinizing hormone—and the gonadotropin releasing hormones—particularly GnRH—are not believed to have any direct actions on bodily functions except through their specific actions on the pituitary and ovaries. In contrast to this limited sphere of action, the steroid hormones, estrogen and progesterone, have a wide range of actions in many tissues. Specialized hormones such as relaxin, placental lactogen, and human chorionic gonadotropin are utilized at certain key intervals to achieve essential endocrinological responses. The female ovary has a dual function in being responsible for both the production and release of the germ cell or ova as well as the biosynthesis and secretion of the key steroid hormones, progesterone and estrogen. These steroid hormones play a dominant role in the differentiation, growth, and maintenance of the sexual reproductive tissues necessary for continuation of the species.

Steroid Hormones: Chemistry, Biosynthesis, and Metabolism

Publisher Summary This chapter discusses the structural chemistry and biosynthetic pathways proven or presumptive of the major classes of steroid hormones. All hormones have complicated structure of fused rings that can be modified by functional group substitution at many points. Furthermore, the presence of asymmetric carbon atoms introduces steric modifications and isomeric possibilities. Over 225 naturally occurring steroids have been isolated and chemically characterized. In addition, an uncountable number of additional steroids and steroid analogs have been chemically synthesized. All steroids belong to the chemical class of substances known as terpenoids or terpenes. Other biologically important terpenoid compounds include the plant hormones gibberellic acid and abscisic acid. All terpenoids have in common the same two C 5 H 8 isoprene precursors employed for their biosynthesis, namely, isopentenyl pyrophosphate and dimethylallyl pyrophosphate. An equally important contribution to the present understanding of the biochemistry of steroids was the introduction and general availability of radioactively-labeled compounds. Radioactive steroids offer two major advantages: The presence of the radioactive label (1) provides a significant increase in sensitivity of the detection of the steroid under study and (2) allows the investigator to detect, either from in vivo whole animal experiments or in vitro experiments with perfused organs, tissue slices, cell suspensions, cell homogenates, or purified enzyme preparations, the presence of new compounds that would otherwise be unappreciated.

Chapter 19 – Cell Growth Factors

This chapter provides an overview of the cell growth factors. Some of the polypeptide hormones have growth factor activities. Hormones that fall within the category of cell growth factors are insulin, somatomedins and growth hormone, prolactin, and erythropoietin. In addition to these better known polypeptide hormones, an increasing list of polypeptides with cell growth-stimulating activities is being generated. Virtually all of these are polypeptides and there are only minor exceptions. In general, growth factors have occurred in very low concentrations in tissues and their isolation, characterization, chemical synthesis, and genetic engineering, where possible, is a continuing effort. Oncogenes are genes that cause cancer and important breakthroughs in the cancer problem developed when oncogene products were shown to be major portions of growth factors or growth factor receptors. These aberrant phenotypes are produced and function in the transformed cell like their normal counterparts except that they may be turned on permanently, thus escaping normal regulation.

Chapter 1 – General Considerations of Hormones

This chapter presents the first principles of hormone action. The chapter discusses in detail about structural and functional classification of hormones and current theories of mechanisms of hormone action at both the cellular and subcellular levels. Hormones are chemical messengers that send a signal within a physiological system from point A to point B. There are four identifiable hormonal communication systems; each has a different anatomical relationship between point A and point B. In classic systemic endocrine system, the hormone is biosynthesized and stored within specific cells associated with an anatomically defined endocrine gland. The hormone is not released until receipt of an appropriate physiological signal, which may take the form of either a change in the concentration of some component in the blood or the delivery of a neural signal. In the paracrine system, the distance from secretion point A to target cell point B is sharply reduced. Here, cell A biosynthesizes and secretes hormone X. Hormone X then diffuses from the secreting cell A to immediately adjacent target cells B. An autocrine system is a variation of the paracrine system where the hormone-secreting cell and the target receptorcontaining cell are one and the same.

Hormones of the Adrenal Medulla

Catecholamines are synthesized and released from adrenergic neurons of the nervous system and together with cholinergic neurons represent two of the major vehicles for chemical neural communication. The adrenergic neurons of the nervous system synthesize and secrete norepinephrine (noradrenaline) and the cholinergic neurons synthesize and secrete acetylcholine. The adrenal medulla is made up of modified neurons no longer possessing axons or nerve endings and is essentially cell bodies that have been adapted to secretory function. In the endocrine sense, the trigger to the adrenal medulla is a unique environmental signal. The catecholamine hormone binds to a receptor on the hepatocyte and elsewhere, generating the breakdown of glycogen to glucose, which is passed into the circulation for use as a ready fuel during stress. Other physiological changes attributable to the adrenal catecholamines include changes in blood pressure and heart functions, which also occur through adrenergic receptors.

Hypothalamic Regulating Hormones

Publisher Summary This chapter discusses hypothalamic regulating hormones. Releasing hormones are produced in various regions of the hypothalamus. In general, the releasing hormones may be thought of as the linkage between electrical/chemical activity of associated regions of the central nervous system (the limbic system) and the beginning of a chemical (hormonal) cascade of messages connecting the hypothalamus, the pituitary, and other organs that secrete the final hormones of the system. Many of these are less than 10 amino acids in length, with short half-lives in serum. When maximal secretion of the ultimate hormone occurs in response to the initial signal, a set of negative feedback reactions takes place, which operate at nearly every level of the cascade mechanism. In general, the anterior pituitary hormones feedback on the cells of the hypothalamus secreting the releasing hormone and inhibiting its further release. This mechanism operates by a hypothalamic cell membrane receptor to regulate the anterior pituitary hormone. Following the ligand binding event, a series of reactions occur that result in shutting down further secretion of the hypothalamic releasing hormone. This feedback link between the anterior pituitary and hypothalamus is called the short feedback loop. Other important negative feedback mechanisms occur between the ultimate hormone and the structures higher up in the cascade.

Pancreatic Hormones: Insulin and Glucagon

Publisher Summary This chapter discusses pancreatic hormones such as insulin and glucagon. A feature essential for life of higher vertebrates is their ability to maintain a relatively constant blood glucose concentration. In the higher animals, glucose is essential as an energy source for all cells. Although some cells can utilize alternate fuel metabolites such as amino acids or fatty acids, the brain and its neurons are dependent upon a continuous supply of blood-delivered glucose. Superimposed on the requirement for the maintenance of a constant blood glucose level are the perturbations in blood glucose that may naturally occur as a consequence of ongoing physiological and metabolic events. Insulin is a potent hormone in that it has a wide sphere of influence; directly or indirectly it affects virtually every organ and tissue in the body. The main functions of insulin are to stimulate anabolic reactions for carbohydrates, proteins, and fats; all of which will have the metabolic consequences of producing a lowered blood glucose level. Glucagon can be thought of as an indirect antagonist of insulin. Glucagon stimulates catabolic reactions that lead ultimately to an elevation of blood glucose levels. Pancreas is continuously adjusting the relative amounts of glucagon and insulin secreted in response to the continuous perturbations of blood glucose and other fuel metabolites occurring as a consequence of changes in anabolism and catabolism in the various tissues.

Posterior Pituitary Hormones

This chapter discusses posterior pituitary hormone. Two important hormones are secreted from the posterior pituitary in both males and females. These are vasopressin (VP), the antidiuretic hormone, and oxytocin (OT), which in females acts as the milk ejection factor. Both are non-apeptides, closely related in structure and apparently derived from the same ancestral gene. The primary recognized function of VP is to stimulate reabsorption of water from the distal tubular kidney. The release of VP is generated by the need to maintain the blood osmolarity of plasma within strict limits (homeostasis), especially with reference to increased Na + concentrations in blood produced by ingestion of NaCl. VP secretion is also increased when blood volume or blood pressure is decreased. VP synthesis in the hypothalamus appear to be close to the osmoreceptor sites that sense changes in electrolyte (solute) concentrations in the circulation and signal release of the hormone from the neuronal terminals in the posterior pituitary. The osmoreceptor is close to the thirst center in the hypothalamus and also interacts with the rennin–angiotensin system. In females, OT plays a major role in milk letdown for nourishing the suckling infant.

CHAPTER 2 – Steroid Hormones: Chemistry, Biosynthesis, and Metabolism

This chapter deals with the structural chemistry and biosynthetic pathways of the major classes of steroid hormones. All steroids belong to the chemical class of substances known as terpenoids or terpenes. Other biologically important terpenoid compounds include the plant hormones gibberellic acid and abscisic acid, insect hormone (juvenile hormone), farnesol (a plant oil), and plant-produced isoprenoids, which include carotene (a precursor of vitamin A), ubiquinone (a vitamin K analog), plastoquinones (participants in photosynthesis), and natural rubber. All steroid hormones have a complicated structure of fused rings, which can be modified by functional group substitution at many points. Furthermore, the presence of asymmetric carbon atoms introduces steric modifications and isomeric possibilities. In mammalian systems, there are six families of steroid hormones that can be classified on both a structural and a biological (hormonal) basis. They are the estrogens (female sex steroids), androgens (male sex steroids), progestins, mineralocorticoids, glucocorticoids, and vitamin D with its daughter metabolites. This chapter discusses in detail about biosynthesis of cholesterol. Properties of enzymes involved in steroidal metabolism are also discussed. The chapter also discusses about plasma transport, catabolism, and excretion of steroid hormones.

Hormones of the Kidney

This chapter discusses the hormones of the kidney. The kidney plays an indispensable role for the maintenance of life in higher organisms not only from the perspective of maintaining the constancy of many components of the extracellular fluid and filtering out of nitrogenous wastes but also as a major endocrine organ. The kidney as an endocrine gland is the site of production of renin and the following hormones: (1) erythropoietin, which is a peptide hormone essential for the process of erythropoiesis or red blood cell formation by the bone marrow; (2) 1,25-dihydroxyvitamin D 3, the hormonally active form of vitamin D which is essential for calcium homeostasis; and (3) the kallikreins, a group of serine proteases that act on blood proteins to produce bradykinin, a potent vasodilator. The kidneys, along with the ureters, urinary bladder, and male or female urethra, comprise the anatomical units responsible for the multiplicity of endocrine, metabolic, and filtering actions of the kidney.