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Hormone Receptors and Their Activation
The first step of a hormone’s action is to bind to specific receptors at the target cell. Cells that lack receptors for the hormones do not respond. Receptors for some hormones are located on the target cell membrane, whereas other hormone receptors are located in the cytoplasm or the nucleus. When the hormone combines with its receptor, this usually initi-ates a cascade of reactions in the cell, with each stage becoming more powerfully activated so that even small concentrations of the hormone can have a large effect.
Hormonal receptors are large proteins, and each cell that is to be stimulated usually has some 2000 to 100,000 receptors. Also, each receptor is usually highly specific for a single hormone; this determines the type of hormone that will act on a particular tissue. The target tissues that are affected by a hormone are those that contain its specific receptors.
The locations for the different types of hormone receptors are generally the following:
1. In or on the surface of the cell membrane. Themembrane receptors are specific mostly for the protein, peptide, and catecholamine hormones.
2. In the cell cytoplasm. The primary receptors forthe different steroid hormones are found mainly in the cytoplasm.
3. In the cell nucleus. The receptors for the thyroidhormones are found in the nucleus and are believed to be located in direct association with one or more of the chromosomes.
The Number and Sensitivity of Hormone Receptors Are Regulated. The number of receptors in a target cell usuallydoes not remain constant from day to day, or even from minute to minute. The receptor proteins them-selves are often inactivated or destroyed during the course of their function, and at other times they are reactivated or new ones are manufactured by the protein-manufacturing mechanism of the cell. For instance, increased hormone concentration and increased binding with its target cell receptors some-times cause the number of active receptors to decrease. This down-regulation of the receptors can occur as a result of (1) inactivation of some of the receptor molecules, (2) inactivation of some of the intracellular protein signaling molecules, (3) tempo-rary sequestration of the receptor to the inside of the cell, away from the site of action of hormones that interact with cell membrane receptors, (4) destruction of the receptors by lysosomes after they are internal-ized, or (5) decreased production of the receptors. In each case, receptor down-regulation decreases the target tissue’s responsiveness to the hormone.
Some hormones cause up-regulation of receptors and intracellular signaling proteins; that is, the stimu-lating hormone induces greater than normal formation of receptor or intracellular signaling molecules by the protein-manufacturing machinery of the target cell, or greater availability of the receptor for interaction with the hormone. When this occurs, the target tissue becomes progressively more sensitive to the stimulat-ing effects of the hormone.
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