Hormone Physiology

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Hormones control a vast array of bodily functions, including sexual reproduction and sexual development, whole-body metabolism, blood glucose levels, plasma calcium concentration, and growth. Hormones are produced in, and released from, diverse places, including the hypothalamus and pituitary, the adrenal gland, the thyroid gland, the testes and ovaries, and the pancreas, and they act on target cells that are often at a considerable physical distance from the site of production. Since they are carried in the bloodstream, hormones are capable of a diffuse whole-body effect, as well as a localized effect, depending on the distance between the production site and the site of action. In many ways the endocrine system is similar to the nervous system, in that it is an intercellular signaling system in which cells communicate via cellular secretions. Hormones are, in a sense, neurotransmitters that are capable of acting on target cells throughout the body, or conversely, neurotransmitters can be thought of as hormones with a localized action.

There are a number of basic types of hormones. Some, such as epinephrine and norepinephrine, originate from the amino acid tyrosine. Other, water-soluble, hormones are derived from proteins or peptides, while the steroid hormones are derived from cholesterol and are thus lipid-soluble. The diversity of the chemical composition of hormones results in a corresponding diversity of mechanisms of hormone action.

Steroid hormones, being lipid-soluble, diffuse across the cell membrane and bind to receptors located in the cell cytoplasm. The resultant conformational change in the receptor leads to activation of specific portions of DNA, thus initiating the transcription of RNA, eventually (possibly hours or days later) resulting in the production of specific proteins that modify cell behavior. An example of one such hormone is aldosterone, whose effect on epithelial cells is to enhance the production of ion channel proteins, rendering the cell more permeable to sodium.

Other hormones, such as acetylcholine, act by binding to receptors located on the cell-surface membrane and causing a conformational change that results in the opening or closing of ionic channels.

Another important mechanism of hormone action is through second messengers, of which there are several examples in this book. Many hormone receptors are linked to G-proteins; binding of a hormone to the receptor results in the activation of the G-protein, and the triggering of a cascade of enzymatic reactions. For example, in the adenylate cyclase cascade, a wide variety of hormones (including adrenocorticotropin, luteinizing hormone, and vasopressin) cause activation of the G-protein, which in turn activates the membrane-bound enzyme adenylate cyclase. This activation results in an increase in the intracellular concentration of cAMP, and the consequent activation of a number of enzymes, with eventual effects on cell behavior; the specific effects depend on the cell type and the type of hormonal stimulus. In Chapters 5 and 12 we described the result of another signaling cascade, the phosphoinositide cascade, in which activation of cell-surface receptors leads to the activation of phospholipase C, the cleavage of phosphotidyl inositol 4,5-bisphosphate, and the resultant production of inositol 1,4,5-trisphosphate (IP3) and diacylglycerol. As we saw, IP3 releases Ca2+ from internal stores, and this can lead to intracellular Ca2+ oscillations and traveling waves.

Hormones can also act by directly converting the receptors into activated enzymes. For example, when insulin binds to a membrane receptor, the portion of the binding protein that protrudes into the cell interior becomes an activated kinase, which then promotes the phosphorylation of several substances inside the cell. The phosphoryla-tion of proteins in the cell leads to a variety of other effects, including the enhanced uptake of glucose.

Much hormonal activity is characterized by oscillatory behavior, with the period of oscillation ranging from milliseconds (0-cell spiking) to minutes (insulin secretion) to hours (^-endorphin). In Table 19.1 are shown examples of pulsatile secretion of various hormones in man. The pulsatility of normal hormonal activity is not completely understood, but has significant implications for the treatment of hormonal abnormalities with drug therapies.

Despite the analogy with neural transmission, there is a significant difference between the endocrine and nervous systems that has important ramifications for mathematical modeling. Not only is the endocrine system extremely complicated, but the data that are presently obtainable are less susceptible to quantitative analysis than, say, voltage measurements in neurons. Further, the distance between the sites of hormone production and action, and the complexities inherent in the mode of transport, make it extraordinarily difficult to construct quantitative models of hormonal control. For these reasons, models in endocrinology are less mechanistic than many of the models presented elsewhere in this book, and thus, in some ways, are less realistic.

Table 19.1 Examples of pulsatile secretion of hormones in man (Brabant et al., 1992.) Different values correspond to different primary sources.



Growth hormone

9-16, 29



Thyroid-stimulating hormone

6-12, 13

Adrenocorticotropic hormone

15, 54

Luteinizing hormone

7-15, 90-121

Follicle-stimulating hormone

4-16, 19









Parathyroid hormone

24-139, 23


108-144, 120

Pancreatic polypeptide





103, 144






8-12, 13




15, 39

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