Hormones and Their Receptors

Chemical Classes of Hormones

The classic hormones can be grouped accord­ing to their chemical structure as peptides, ste­roids, or amines. The amines are biochemical modifications of a single amino acid, tyrosine.

Eicosanoids

Eicosanoid is a general term for compounds that are chemical derivatives of long-chain fatty acids. Prostaglandins, thromboxanes, and leu­kotrienes are eicosanoids that function as chemical messengers. Arachidonic acid, a com- ponent of cell membranes, is the precursor fatty acid in most cases. While these agents are not classic hormones, they are important chemical messengers involved in the regulation of vastly different physiologic functions. in most cases, prostaglandins, thromboxanes, and leukotri­enes act as paracrine agents, for they function near their site of origin and are rapidly metabo­lized after entering the bloodstream. This rapid metabolism in the blood is true for many para­crine agents and is a factor that contributes to their characteristic localized effect.

Prostaglandins have been isolated from nearly every tissue of the animal body, although they derive their name from the prostate gland from which they were originally isolated. There are a number of prostaglandins. Each has a slight difference in chemical structure, and each may have multiple regulatory functions in a variety of tissues. Furthermore, one prosta­glandin may have opposite physiologic effects in different organs. in general terms, prosta­glandins are implicated in regulation of blood vessel diameter, inflammation, blood clotting, uterine contraction during parturition, and ovulation, among many others. Because pros­taglandins are important in many reproductive functions, these substances will be revisited in Chapter 27.

Leukotrienes are similar in structure to pros­taglandins, being produced from arachidonic acid via a different enzymatic pathway. There are several families of related leukotrienes, each with specific functions. Leukotrienes are pro­duced primarily by monocytes and mast cells and are usually associated with allergic reac­tions. Release of leukotrienes increases vascu­lar permeability and induces constriction of airways; in humans, these substances have been implicated in producing some of the most pro­longed manifestations of asthmatic attacks.

Because of the prominent role of prosta­glandins as mediators of inflammation, drugs that inhibit prostaglandin synthesis are anti­inflammatory. These are the nonsteroidal anti-inflammatory drugs, or NSAIDs, of which aspirin and ibuprofen are widely used over- the-counter varieties. The side effects of these drugs (e.g., gastric ulceration and kidney injury) occur due to the indiscrimi­nate inhibition of both undesirable effects (i.e., inflammation) and important desirable effects (e.g., maintenance of blood flow to stomach and kidneys). Most NSAIDs also inhibit the formation of thromboxanes, because some of the same enzymes are involved in the synthesis pathways for pros­taglandins and thromboxanes. Aspirin reduces the synthesis of thromboxanes for blood clotting, and this is part of the ratio­nale for their use in animals and people to reduce the potential for clot formation. Newer NSAIDs have been developed to inhibit only the production of prostaglan­dins associated with inflammation.

Hormone Receptors

only certain specific populations of cells respond to an individual hormone. The term target organ is used to identify the tissue whose cells will be affected by a given hormone. Some hormones have multiple target organs, for they affect cells in several sites. For example, both skeletal muscle and liver are among the target organs for insulin. Table 12-1 lists the major endocrine glands, their hormones, and their general effects on their target organs.

Cells within target organs are capable of rec­ognizing and responding to a given hormone because they contain specific receptors capable of binding, or forming a chemical union, with the hormone. As described in Chapter 2, these cellular receptors may be components of the cell membrane and have a binding site exposed to the extracellular fluid, or they may be con­tained within the cytoplasm or nucleus of cells. in either case, a receptor for a specific hormone must be present for a cell to respond to the hormone.

The presence and number of receptors within target cells may change in certain condi­tions. Such changes are one way that the bio­logic effect of a given hormone can be regulated. For example, levels of estrogen, a reproductive hormone, increase in circulation shortly before birth (parturition), and this stimulates an

Table 12-1. Major Endocrine Glands, the Hormones They Secrete, and Primary Action and Target Tissue of the Hormones

ACTH, corticotrophin; ADH, antidiuretic hormone, also called arginine vasopressin; CRH, corticotropin­releasing hormone; FSH, follicle-stimulating hormone; GH, growth hormone; GHIH, growth hormone- inhibiting hormone; GHRH, growth hormone-releasing hormone; GnRH, gonadotropin-releasing hormone; LH, luteinizing hormone; PRL, prolactin; PTH, parathyroid hormone; TRH, thyrotrophin-releasing hormone; TSH, thyrotrophin.

increase of oxytocin receptors in the smooth muscle of the uterus.