Protein Hormones Have Specific Receptors on Target Tissue Plasma MembranesrWhereas Steroids Have Specific ReceptorsWithin the Cytoplasm or Nucleus
A central question in endocrinology is how hormones and target cells of a particular tissue interact in a specific manner. The problem seems almost overwhelming for steroids because they are lipid soluble and able to permeate all cells of the body.
The solution is that target cells have receptors that are specific for a particular hormone. For steroids, the receptors are located in the cytoplasm or nucleus of the target cells, whereas receptors for protein and peptide hormones are located on the plasma membrane of the cell. In addition to specificity, receptors have a high affinity for their respective hormone. These characteristics of the receptor allow hormones to be in low concentration in the blood but effective in producing significant tissue response.The greater the affinity of the receptor for the hormone, the longer is the biological response. Termination of the action of a hormone usually requires dissociation of the hormone from the receptor. This occurs most often as a result of a decrease in plasma concentrations of the hormone; the binding of receptor and hormone is noncovalent, and declining hormone concentrations favor a chemical equilibrium of dissociation over association. Termination of hormone action can also result from internalization of the receptor-hormone complex through the process of endocytosis. The hormone is degraded by lysosomal enzymes, whereas the receptor, protected because of its association with the vesicle membrane, can be recycled to the plasma membrane.
Receptors are present on cells in much greater numbers than required for the elicitation of a biological response. Occupancy by a hormone of considerably less than 50% of the receptors usually elicits a maximal biological response. Even so, changes in receptor numbers that affect the sensitivity of the cell, although not its maximal responsiveness, can occur. Changes in receptor number affect the probability that an interaction will occur between receptor and hormone. Receptor synthesis can be stimulated by a hormone that is different from the hormone that interacts with the receptor. For example, predominant gonadotropin receptors on ovarian granulosa cells change from FSH to LH receptors late in the ovarian follicle phase because of the influence of FSH. This allows the control of the ovarian follicle to pass from FSH to LH, which facilitates ovulation and the formation of a corpus luteum. Conversely, receptor numbers can decrease in conjunction with continued interaction of receptor and hormone. This often occurs when an agonist that has great affinity for the receptor is administered or when amounts of hormone are pathologically elevated. The receptor numbers are downregulated in this situation. The end result is that the animal becomes resistant to continued therapy with the hormone in question.