Progesterone and testosterone in combination act in the hypothalamus of castrated rams to regulate the secretion of LH

We tested the hypotheses that progesterone enhances the negative feedback a ctions of testosterone in rams and that this occurs through actions at the hypothalamus. In the first part of this study, blood samples were collected every 10 min for 12 h before and after 7 days of treatment (i.m.) of castr ated Romney Marsh rams (n=5 per group) with vehicle, progesterone (4 mg/12 h), testosterone (4 mg/12 h) or a combination of progesterone (4 mg/12 h) a nd testosterone (4 mg/12 h). In the second part of this study the: brains o f four gonad-intact Romney Marsh rams were collected, the hypothalamus was sectioned and in situ hybridisation of mRNA for progesterone receptors cond ucted. After 7 days of treatment with vehicle or progesterone or testostero ne alone, there were no changes in the secretion of LH, In contrast. treatm ent with a combination of progesterone and testosterone resulted in a signi ficant (P <0.01, repeated measures ANOVA) decrease in mean plasma concentra tions of LH, the number of LH pulses per hour and the pre-LH pulse nadir an d a significant (P <0.01) increase in the inter-LH pulse interval. We found cells containing mRNA for progesterone receptors throughout the hypothalam us, including the preoptic area (where most GnRH neurons are located in she ep), the periventricular, ventromedial and arcuate nuclei and the bed nucle us of the stria terminalis. This study shows that progesterone is capable o f acting centrally with testosterone to suppress the secretion of LH ill ca strated rains and that cells containing mRNA for progesterone receptors are located ill the hypothalamus of rams in the vicinity of GnRH neurons.