Human placental gonadotrophin-releasing hormone (GnRH) binding sites: III. Changes in GnRH binding levels with stage of gestation

We have measured the levels of gonadotrophin-releasing hormone (GnRH) binding sites in human placental villous membrane fractions obtained at different stages of gestation. There was a marked decrease in the specific activity of 125I-labelled GnRH binding to membrane fractions obtained between 10–20 weeks gestation, but there was no change in either affinity or ligand specificity of these binding sites. The observed decrease in binding was not due to contamination of placental villous membranes by membranes from other tissues, since there was no gestation-dependent decrease in the specific activity of epidermal growth factor receptor or alkaline phosphatase activity in villous membrane fractions between 10–20 weeks of gestation. Furthermore, incubation of GnRH tracer with membranes from different stages of gestation, followed by re-incubation of the unbound tracer fraction with fresh membranes, demonstrated unequivocally that decreased GnRH binding to 10–20 week membranes was not due to increased degradation of GnRH tracer. We conclude that the observed changes in GnRH receptor levels between 10–20 weeks gestation must reflect either decreased expression/synthesis (or increased catabolism) of placental GnRH receptors, or increased occupancy (or down-regulation) of placental GnRH receptors by an endogenous GnRH-like ligand.