Absence of gonadotropin-releasing hormone receptors in human gonadal tissue.

Abstract

The antifertility nature of the hypothalamic peptide gonadotropin releasing hormone (GnRH) and its synthetic agonist analogue (GnRH-A) has been repeatedly demonstrated in rodents, monkeys and humans (see ref. 1 for review). In all species studied, this action of GnRH was initially attributed to ‘desensitization’ of gonadal steroidogenesis due to loss of gonadotropin receptors in the testis and ovary, induced by high circulating levels of endogenous gonadotropins achieved following repeated administration of GnRH or GnRH-A2–5. Recently, an additional, direct inhibitory action of these peptides on ovarian granulosa6,7 and luteal8–10 and testicular Leydig11–13 cells has been defined. This direct inhibition of gonadal steroidogenesis is mediated through specific high-affinity GnRH receptors in the respective target tissues8,9,12,14. These receptors exhibit identical characteristics to GnRH receptors (GnRH-R) in rodent anterior pituitary tissue9,12,14,15. In the search for a naturally occurring ligand for gonadal GnRH-R, a biologically active ‘GnRH-like’ peptide has been isolated from rat ovary16 and testis17,18, and from monkey testis interstitial fluid18. These findings suggest the production in rodent gonads of a GnRH-like peptide which, following interaction with gonadal GnRH-R, serves as a local modulator of steroidogenesis, and hence of reproductive capacity. If a similar situation exists in humans, GnRH-R should be detectable also in the human testis and ovary. We report here that we have been unable to detect any binding of radiolabelled GnRH-A to human corpus luteum or testis, or to the monkey testis. In contrast, GnRH-R were detected in adult and fetal human anterior pituitary tissue. Thus, we suggest that a direct inhibitory action of GnRH on primate reproductive function is unlikely. Furthermore, this important species difference highlights the need for a re-evaluation of certain rodent models designed to investigate primate, and especially human, reproductive physiology.