Hormonal regulation of membrane receptors and cell responsiveness: a review

Hormone receptors are those components of target-cells that specifically bind hormones and convey the hormonal message to the intracellular machinery. Such receptors can be localized inside the cell, such as the nuclear receptors of thyroid hormones and the nuclear and cytoplasmic receptors of steroid hormones, or on the outer surface of the plasma membrane, such as the membrane-bound receptors of polypeptide hormones and neurotransmitters. Extensive studies during recent years have shown that the interaction between hormone and membrane-bound receptor can affect the receptor characteristics in at least two ways. Firstly, receptor occupancy can modify, by way of cooperativity, the affinity of homologue receptors for the given hormone. Secondly, the binding capacity of a target cell appears to vary as a function of the preexposure of the cell to the hormone. The latter phenomenon has been related to the so-called states of subsensitivity, desensitization, or refractoriness, and might be responsible for the physiologic regulation of the target cell sensitivity and for the hormone resistance which accompanies various metabolic disorders. In this review we attempt to describe the major findings related to hormone desensitization or resistance of these hormones that have plasma-membrane-bound receptors. Data from the literature are presented independently for each hormone and when applicable, conflicting results are discussed in each section. The various theories which might explain hormone desensitization are outlined in the last section of this paper.