Chapter 520

A hormone is a molecule that is secreted into the circulation to influence the function of target cells in another tissue or organ. In addition to distant targets via the circulation (endocrine action), many hormones also influence the function of the cells that secreted them (autocrine action) or that of adjacent cells (paracrine action). For example, when insulin, produced by pancreatic beta cells, stimulates glucose storage and oxidation, protein synthesis, and lipid storage in the liver, muscle and fat, it is acting in an endocrine fashion; when it inhibits glucagon secretion by the nearby pancreatic alpha cells, it is acting in a paracrine fashion. Frequently, the endocrine and autocrine/paracrine actions of a hormone lead to the same effect. For example, growth hormone (GH) stimulates hepatic production of insulin-like growth factor I (IGF-I), the main mediator of somatic growth in childhood. It has been shown that mice with targeted deletion of IGF-I expression in only the liver grow to normal size, despite a 75% reduction in their circulating IGF-I concentration.1 This seminal experiment demonstrated the importance of autocrine and paracrine IGF-I production to body growth.

Hormone actions are mediated via systems with similar basic components. This chapter will describe the specific components of the major categories of hormones and will provide a methodological overview of how these hormones contribute to health and disease. Each system is characterized by the gland that produces a hormone, the hormone itself, and often circulating binding proteins. The binding proteins create a circulating pool of readily available hormone stores, alter hormone clearance and distribution, and modulate hormone activity rates. Binding of the free hormone, the ligand, to specific receptors on the target cells initiates a variety of signal transduction pathways, often through a series of signaling cascades or second messengers that alter cell function. The impact of the hormonal message on cell function is often modified by other regulatory molecules that modulate the activity of these signaling pathways.

Hormones are categorized based on their molecular structure. Most are peptide hormones, made of amino acid chains. Small neuropeptide hormones include antidiuretic hormone (ADH), gonadotropin-releasing hormone (GnRH), and thyrotropin-releasing hormone (TRH). Larger peptide hormones, known as protein hormones, include insulin and growth hormone (GH). Glycoprotein hormones have carbohydrate side chains attached; these include human chorionic gonadotropin (hCG), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and thyroid-stimulating hormone (TSH). Amino acid–derived peptide hormones have an NH2 group at the end of the molecule and arise from the amino acids tyrosine and tryptophan. These include thyroxine, dopamine, catecholamines, and melatonin. In general, peptide hormones work through cell surface receptors.

In contrast, steroid hormones are lipid and phospholipid derivatives. These hormones are synthesized from cholesterol (eg, testosterone, cortisol) or the eicosanoids (prostaglandins) by a series of enzymatic steps. Other hormones are vitamin derivatives, including the retinoids (vitamin A) and vitamin D. In general, thyroid hormones, steroid hormones, retinoids, and vitamin D are lipid-soluble and work ...

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