Pyroglutamylated RFamide peptide 43 stimulates the hypothalamic-pituitary-gonadal axis via gonadotropin-releasing hormone in rats

Although it is established that other members of the RFamide family stimulate the hypothalamic-pituitary-gonadal axis, the influence of the novel pyroglutamylated RFamide peptide 43 (QRFP43) is not known. We show intracerebroventricular (icv) administration of QRFP43 (2 nmol) to male rats increased plasma LH and FSH levels at 40 min after injection. icv administration of 3 nmol QRFP43 did not affect food intake in ad-libitum-fed male rats. The icv administration of 2 nmol QRFP43 did not significantly influence behavior in male rats. Intraperitoneal administration of doses up to 1200 nmol/kg QRFP43 in male rats did not significantly influence circulating gonadotropin or sex steroid levels. In vitro, QRFP43 stimulated GnRH release from hypothalamic explants from male rats and from GT1-7 cells. Pretreatment with a GnRH receptor antagonist, cetrorelix, blocked the increase in plasma LH levels after icv administration of QRFP43 (2 nmol). These results suggest that icv QRFP43 activates the hypothalamic-pituitary-gonadal axis via GnRH.