Agouti Related Peptide (Agrp) Stimulates the Hypothalamo Pituitary Gonadal Axis in Vivo & in Vitro in Male Rats

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Abstract
Agouti related peptide (Agrp), the endogenous antagonist of the melanocortin 3 and 4 receptors (MC3-R and MC4-R), is expressed at high levels in the arcuate nucleus. Agrp immunoreactive terminals are found in the medial preoptic area (MPO), an area that also contains luteinizing hormone releasing hormone (LHRH) neurons. This study was designed to examine the action of Agrp and αMSH on gonadotropin release in vivo following intracerebroventricular (ICV) injection and on LHRH and luteinizing hormone (LH) release in vitro in male rats. We report that ICV administration of Agrp (83–132) significantly increased plasma LH at 40 min post-injection (Agrp (83–132) 2 nmol 0.6 ± 0.1 vs. saline 0.4 ± 0.02 ng/ml, p < 0.05). Plasma follicle stimulating hormone (FSH) was also significantly increased by Agrp (83–132) at 40 min post-injection (Agrp (83–132) 2 nmol 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 basal hypothalamic explants (Agrp (83–132) 100 nM 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 pituitary cells (Agrp (83–132) 100 nM 10 ± 0.4 ng/ml vs. control 12 ± 1.3 ng/ml, p = ns; LHRH 10 nM + Agrp (83–132) 100 nM 28 ± 1.5 ng/ml vs. LHRH 10 nM 28 ± 1.2 ng/ml, p = ns). We have demonstrated that Agrp (83–132), which blocks melanocortin receptors, significantly increases plasma LH and FSH following ICV administration and stimulates LHRH release from hypothalamic explants but has no direct effect on LH release from dispersed anterior pituitary 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.

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