Administration of ghrelin, a key peptide in the regulation of energy homeostasis, has been shown to decrease LH pulse frequency while concomitantly elevating cortisol levels. Because increased endogenous CRH release in stress is associated with an inhibition of reproductive function, we have tested here whether pulsatile LH decrease following ghrelin may reflect an activated HPA axis and be prevented by a CRH antagonist. After a 3h baseline LH pulse frequency monitoring, 5 adult OVX rhesus monkeys received a 5h- saline (protocol 1) or ghrelin infusion (100µg bolus followed by 100µg/h, protocol 2). In protocols 3 and 4, animals were given astressin B, a non specific CRH receptor antagonist (0.45mg/kg im), 90 min prior to ghrelin or saline infusion. Blood samples were taken every 15 min for LH measurements, while cortisol and GH were measured every 45 min. Mean LH pulse frequency during the 5h ghrelin infusion was significantly lower than in all other treatments (p<0.05) and when compared to the baseline period (p<0.05). Pretreatment with astressin B prevented the decrease. Ghrelin stimulated cortisol and GH secretion, while astressin B pretreatment prevented the cortisol, but not the GH, release. Our data indicate that CRH release mediates the inhibitory effect of ghrelin on LH pulse frequency and suggest that the inhibitory impact of an insufficient energy balance on reproductive function may in part be mediated by the HPA axis.