Hormone Activity

Although a given hormone travels throughout the body in the blood, it affects only specific target cells. Hormones, like neurotransmitters, influence their target cells by chemically binding to specific protein receptors. Only the target cells for a given hormone have receptors that bind and recognize that hormone. For example, thyroid-stimulating hormone (TSH) binds to receptors on cells of the thyroid gland, but it does not bind to cells of the ovaries because ovarian cells do not have TSH receptors.

Receptors, like other cellular proteins, are constantly being synthesized and broken down. Generally, a target cell has 2000 to 100,000 receptors for a particular hormone. If a hormone is present in excess, the number of target-cell receptors may decrease—an effect called down-regulation. For example, when certain cells of the testes are exposed to a high concentration of luteinizing hormone (LH), the number of LH receptors decreases. Down-regulation makes a target cell less sensitive to a hormone. In contrast, when a hormone is deficient, the number of receptors may increase. This phenomenon, known as up- regulation, makes a target cell more sensitive to a hormone.

Most endocrine hormones are circulating hormones—they pass from the secretory cells that make them into interstitial fluid and then into the blood. Other hormones, termed local hormones, act locally on neighboring cells or on the same cell that secreted them without first entering the bloodstream. Local hormones that act on neighboring cells are called paracrines, and those that act on the same cell that secreted them are called autocrines. One example of a local hormone is interleukin 2 (IL-2), which is released by helper T cells (a type of white blood cell) during immune responses (see Chapter 22). IL-2 helps activate other nearby immune cells, a paracrine effect. But it also acts as an autocrine by stimulating the same cell that released it to proliferate. This action generates more helper T cells that can secrete even more IL-2 and thus strengthen the immune response. Another example of a local hormone is the gas nitric oxide (NO), which is released by endothelial cells lining blood vessels. NO causes relaxation of nearby smooth muscle fibers in blood vessels, which in turn causes vasodilation (increase in blood vessel diameter). The effects of such vasodilation range from a lowering of blood pressure to erection of the penis in males. The drug Viagra® (sildenafil) enhances the effects stimulated by nitric oxide in the penis.

Local hormones usually are inactivated quickly; circulating hormones may linger in the blood and exert their effects for a few minutes or occasionally for a few hours. In time, circulating hormones are inactivated by the liver and excreted by the kidneys. In cases of kidney or liver failure, excessive levels of hormones may build up in the blood.

Chemically, hormones can be divided into two broad classes: those that are soluble in lipids, and those that are soluble in water. This chemical classification is also useful functionally because the two classes exert their effects differently.

The lipid-soluble hormones include steroid hormones, thyroid hormones, and nitric oxide.

1. Steroid hormones are derived from cholesterol. Each steroid hormone is unique due to the presence of different chemical groups attached at various sites on the four rings at the core of its structure. These small differences allow for a large diversity of functions.

2. Two thyroid hormones ( T3 and T4 ) are synthesized by attaching iodine to the amino acid tyrosine. The benzene ring of tyrosine plus the attached iodines make T3 and T4 very lipid soluble.

3. The gas nitric oxide (NO) is both a hormone and a neurotransmitter. Its synthesis is catalyzed by the enzyme nitric oxide synthase.

The water-soluble hormones include amine hormones, peptide and protein hormones, and eicosanoid hormones.

1. Amine hormones are synthesized by decarboxylating(removing a molecule of CO2) and otherwise modifying certain amino acids. They are called amines because they retain an amino group. The catecholamines—epinephrine, norepinephrine, and dopamine—are synthesized by modifying the amino acid tyrosine. Histamine is synthesized from the amino acid histidine by mast cells and platelets. Serotonin and melatonin are derived from tryptophan.

2. Peptide hormones and protein hormones are amino acid polymers. The smaller peptide hormones consist of chains of 3 to 49 amino acids; the larger protein hormones include 50 to 200 amino acids. Examples of peptide hormones are antidiuretic hormone and oxytocin; protein hormones include human growth hormone and insulin. Several of the protein hormones, such as thyroid-stimulating hormone, have attached carbohydrate groups and thus are glycoprotein hormones.

3. The eicosanoid hormones are derived from arachidonic acid, a 20-carbon fatty acid. The two major types of eicosanoids are prostaglandins and leukotrienes. The eicosanoids are important local hormones, and they may act as circulating hormones as well.

Most water-soluble hormone molecules circulate in the watery blood plasma in a “free” form (not attached to other molecules), but most lipid-soluble hormone molecules are bound to transport proteins. The transport proteins, which are synthesized by cells in the liver, have three functions:

1. They make lipid-soluble hormones temporarily water-soluble, thus increasing their solubility in blood.

2. They retard passage of small hormone molecules through the filtering mechanism in the kidneys, thus slowing the rate of hormone loss in the urine.

3. They provide a ready reserve of hormone, already present in the bloodstream.

In general, 0.1–10% of the molecules of a lipid-soluble hormone are not bound to a transport protein. This free fraction diffuses out of capillaries, binds to receptors, and triggers responses. As free hormone molecules leave the blood and bind to their receptors, transport proteins release new ones to replenish the free fraction.