Gonadotropins and ovarian gonadotropin receptors during the perimenopausal transition period

Abstract

As an early sign of perimenopause, the menstrual cycles become irregular. Associated with this irregularity, serum gonadotropin levels increase. There are studies correlating these changes to ovarian follicular morphology and number, but no reports are available, to our knowledge, correlating the increases in gonadotropin levels to respective cellular receptors. In fact, the regulation of gonadotropin receptors is poorly understood in the human. The action of gonadotropins on gonadal function is mediated through specific binding of the hormones to receptors located on the surface of target cells followed by activation of intracellular second messenger systems. In the ovary, the target cells for FSH are granulose cells of ovarian follicles, while the action of LH is mediated through binding of the ligand to theca, granulosa and luteal cells. The cell-surface receptors for gonadotropins are located respectively on these cell types. The molecular nature of FSH receptors and LH receptors has been characterized in many species, and their structure is well-known both on the protein and nucleic acid level. Despite the vast amount of studies in rodents, there is limited information available on the regulation of gonadotropin receptors in the human. In a recent study, serum LH and FSH levels were correlated to respective receptor levels in ovarian tissue in order to better understand gonadotropin action and the physiology of the menopause in the human. High serum gonadotropin levels in perimenopause suggested the existence of low ovarian gonadotropin receptor levels. In most patients who are still experiencing cyclic menstrual bleeding no FSH receptors were detected possibly due to severe disturbances in follicular FSH receptor synthesis prior to ovarian follicle exhaustion.