Chapter 38

### ENDOCRINOLOGY AND HORMONES: GENERAL CONCEPTS

Endocrinology analyzes the biosynthesis of hormones, their sites of production, and the sites and mechanisms of their action and interaction. The term hormone is of Greek origin and classically refers to chemical messengers that circulate in body fluids and produce specific effects on cells distant from their point of origin. The major functions of hormones include the regulation of energy storage, production, and utilization; the adaptation to new environments or conditions of stress; the facilitation of growth and development; and the maturation and function of the reproductive system. Although hormones were originally defined as products of ductless glands, we now appreciate that many organs that were not classically considered as "endocrine" (e.g., the heart, kidneys, GI tract, adipocytes, and brain) synthesize and secrete hormones that play key physiological roles; many of these hormones are now employed either diagnostically or therapeutically in clinical medicine. In addition, the field of endocrinology has expanded to include the actions of growth factors acting by means of autocrine and paracrine mechanisms, the influence of neurons—particularly those in the hypothalamus—that regulate endocrine function, and the reciprocal interactions of cytokines and other components of the immune system with the endocrine system.

As discussed in Chapter 3, hormones generally exert their actions on target cells via a plenitude of receptors, including heptaspanning GPCRs, monospanning membrane tyrosine kinases and guanylyl cyclases, cytokine receptors, ligand-activated ion channels, and nuclear transcription factors. Conceptually, it is useful to divide hormones into two classes: those that act predominantly via nuclear receptors to modulate transcription in target cells and those that typically act via membrane receptors to exert rapid effects on signal transduction pathways. Steroid hormones, thyroid hormone, and vitamin D belong to the first class, whereas peptide and amino acid hormones are generally assigned to the second class. The receptors for both classes of hormones provide tractable targets for a diverse group of compounds that are among the most widely used drugs in clinical medicine.

### DISORDERS OF ENDOCRINE REGULATION

Because of their potent effects, circulating levels of hormones generally are tightly regulated within a normal range. The physiological strategies used to maintain the appropriate levels of hormones range from relatively simple ones involving direct feedback or feed-forward mechanisms (e.g., the secretion of parathyroid hormone by the parathyroid glands is inversely related to the serum Ca2+ concentration, which is sensed by a GPCR termed the Ca2+-sensing receptor; Chapter 44) to more complex ones involving reciprocal interactions among the hypothalamus, anterior pituitary, and endocrine glands (see the section "The Hypothalamic-Pituitary-Endocrine Axis").

Regardless of the mechanism, normal regulation can be perturbed in disease states when a given hormone is either over or underproduced or when its signaling mechanisms are impaired. Understanding the normal regulation and actions of the various hormones is critical to both diagnosis and treatment of these endocrine disorders. Chapters 38,...

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