: OBJECTIVES: Corticotropin-releasing hormone (CRH) and leptin (LEP) are two neuropeptides involved in the regulation of food intake, energy homeostasis and stress response. These neuropeptides play an important role in the regulation of the hypothalamo-pituitary-gonadal (HPG) axis, too. It is known that leptin can affect the synthesis and release of CRH in the hypothalamus. There is no information about interactions between CRH and leptin directly in gonads. The aim of this study was to evaluate the effects of leptin and CRH on progesterone (P4) release from cultured rat granulosa cells obtained from mature rats in diestrus. METHODS: Granulosa cell cultures were maintained with CRH, LEP, CRH + LEP and CRH-antagonist in varying concentrations. P4 supernatant concentrations were determined by RIA method. RESULTS: CRH stimulated P4 release, CRH-antagonist had no effect on P4 release alone but inhibited the CRH-stimulated P4 release, and the effect of leptin depended on concentration and on time of incubation. CONCLUSION: Our results show that leptin, beside its own influence, may effect on ovarian steroidogenesis through its interaction with effects of CRH activity. This is a new additional link between the stress response, body weight and reproductive functions.