Chapter 513: Mechanisms of Hormone Action

INTRODUCTION

Hormones are molecules 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. Mice with targeted hepatic deletion of IGF-I expression grow to normal size, despite a 75% reduction in circulating IGF-I concentrations. This seminal experiment demonstrated the importance of autocrine and paracrine IGF-I production by other tissues to body growth.

Hormone actions are mediated via systems with similar basic components. This chapter will describe components of the major classes of hormones and will provide a methodologic overview of how hormones within each class contribute to health and disease. Each system is characterized by the gland that produces a hormone, the hormone itself, and often binding proteins. These circulating binding proteins create a pool of readily available hormone stores, alter hormone clearance and distribution, and modulate hormone activity. Free hormone “ligand” binding to specific target cell receptors 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.

HORMONE CLASSIFICATION

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 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 through intracellular receptors.

HORMONE RECEPTOR CLASSIFICATION