Agouti related peptide (Agrp) stimulates the hypothalamo pituitary gonadalaxis in vivo & in vitro in male rats.

Agouti related peptide (Agrp), the endogenous antagonist of the melanocorti n 3 and 4 receptors (MC3-R and MC4-R), is expressed at high levels in the a rcuate nucleus. Agrp immunoreactive terminals are found in the medial preop tic area (MPO), an area that also contains luteinizing hormone releasing ho rmone (LHRH) neurons. This study was designed to examine the action of Agrp and alpha MSH on gonadotropin release in vivo following intracerebroventri cular (ICV) injection and on LHRH and luteinizing hormone (LH) release ii? vitro in male rats. We report that ICV administration of Agrp (83-132) significantly increased plasma LK at 40min post-injection (Agrp (83-132) 2nmol 0.6 +/- 0.1 vs. sali ne 0.4 +/- 0.02 ng/ml, p<0.05). Plasma follicle stimulating hormone (FSH) w as also significantly increased by Agrp (83-132) at 40min post-injection (A grp (83-132) 2nmol 15.6 +/- 2.1 ng/ml vs. saline 9.6 +/- 1.1 ng/ml, p<0.05) . Agrp (83-132) significantly stimulated the release of LHRH from medial ba sal hypothalamic explants (Agrp (83-132) 100nM 170 +/- 23% vs. control 100 +/-: 20 %, p < 0.05). In contrast, Agrp (83-132) (0.1-100 nM) had no effect on either basal or LHRH-stimulated LH release from dispersed anterior pitu itary cells (Agrp (83-132) 100nM 10 +/- 0.4 ng/ml vs, control 12 +/- 1.3 ng /ml, p = ns; LHRH 10nM + Agrp (83-132) 100nM 28 +/- 1.5 ng/ml vs. LHRH 10nM 28 +/- 1.2 ng/ml, p = ns). We have demonstrated that Agrp (83-132), which blocks melanocortin receptors, significantly increases plasma LH and FSH fo llowing ICV administration and stimulates LHRH release from hypothalamic ex plants but has no direct effect on LH release from dispersed anterior pitui tary cells. These results suggest that the melanocortin system plays a role in the control of the hypothalamo-pituitary gonadal axis and may act as a link between the control of appetite and reproductive function.