Oestradiol microimplants in the ventromedial preoptic area inhibit secretion of luteinizing hormone via dopamine neurones in anoestrous ewes

Oestradiol exerts a season-specific negative feedback effect on the GnRH/LH neurosecretory system of the Suffolk ewe. This neuroendocrine suppression is mediated in part by dopamine A15 neurones, but these neurones do not pos sess the oestrogen receptor. Based on indirect evidence, we hypothesized th at oestrogen receptor-containing neurones in the ventromedial preoptic area (vmPOA) may be the initial step in a neuronal system whereby oestradiol su ppresses GnRH secretion during the non-breeding season. To test this, three experiments were conducted using ovariectomized ewes receiving either empt y or oestradiol-containing bilateral microimplants directed at the vmPOA or s.c. subcutaneous oestradiol-containing implants. In the first experiment, LH pulse frequency was measured on days 0, 1, 7 and 14 of treatment during seasonal anoestrus. In vmPOA oestradiol and s.c. oestradiol groups only, L H pulse frequency was suppressed on days 7 and 14, with maximal suppression evident by day 7. In the second experiment, this protocol was repeated dur ing the breeding season, with LH pulses examined on days 0 and 7; LH pulse frequency did not change in any group. The third experiment tested if the e ffect of vmPOA oestradiol during anoestrus could be overcome by an injectio n of the dopamine-D-2 receptor antagonist (-)-sulpiride. The vmPOA microimp lants and s.c. oestradiol implants again suppressed LH pulse frequency and this was reversed by sulpiride in vmPOA oestradiol ewes. We conclude that o estradiol acts on cells in the vmPOA to stimulate a system involving dopami ne neurones that inhibits GnRH/LH pulsatility in the anoestrous ewe.