Hypothalamic releasing-hormone receptors

Abstract

With the availability of synthetic analogues of the hypothalamic releasing hormones, analysis of their interactions with pituitary receptors has been achieved. The most studied is gonadotrophin-releasing hormone (GnRH). Pituitary receptors for this peptide show a positive correlation with gonadotrophin secretion and responsiveness to exogenous GnRH in experimental animals, an indication of their physiological importance. GnRH is also required for maintenance of a 'normal' complement of GnRH receptors and, when administered intermittently, can effect significant increases in unoccupied receptors. Conversely, the continuous administration of high GnRH or agonist analogue (GnRH-A) doses leads to pituitary desensitization through disruption of receptor-mediated events. Thus, for stimulation of fertility using GnRH, the peptide should be administered in small doses at physiological frequency (approximately once every two hours) to avoid pituitary desensitization. The desensitizing properties of long-acting GnRH-A are of potential value as contraceptives agents and where a medical castration is desirable. The physiological correlates of pituitary receptors for thyrotrophin-releasing hormone, somatostatin (GHRIH) and corticotrophin-releasing factor await elucidation.