Functional consequences of the phosphorylation of the gonadotropin receptors

When target cells are exposed to a hormone, their responsiveness wanes with time, in spite of the continuous presence of the hormone. This phenomenon, referred to as desensitization, is due to regulatory steps that occur at the level of the hormone receptor as well as at post-receptor steps. While post-receptor events may be specific for the metabolic pathways activated in a given target cell, receptor events are more general in nature and conserved within a given family of receptors. There are at least two categories of regulatory events that occur at the level of the receptor and contribute to the process of desensitization. One of them, referred to as receptor uncoupling, will be used here to denote a change in the functional properties of a constant number of receptors resulting in a reduction in the ability of the receptor to activate its most proximal effector system. The other, referred to as receptor down-regulation, will be used here to denote a reduction in the density of cell surface receptors. Uncoupling is generally faster than down-regulation, and is believed to be due to post-translational modifications of the receptor. Down-regulation, on the other hand, is slower, and could be due to an increase in the rate of receptor internalization, sequestration or degradation, and/or to a decrease in the rate of receptor externalization, processing or synthesis. In this paper, recent studies from my laboratory designed to directly address the potential involvement of gonadotropin receptor phosphorylation in the process of uncoupling have been reviewed.