Evidence that catecholaminergic and peptidergic (luteinizing hormone-releasing hormone) neurons in suprachiasmatic-medial preoptic, medial basal hypothalamus and median eminence are involved in estrogen-negative feedback.

A time-course study was performed to correlate serum gonadotropin changes after ovariectomy (OVX) or OVX plus acute estradiol (E2) treatment with LHRH content and norepinephrine (NE) and dopamine (DA) content and turnover in the suprachiasmatic-medial preoptic region (SCH-PO), the medial basal hypothalamus (MBH), and the median eminence (ME). Rats on diestrous day 1 (D1) were sham operated to serve as controls or were ovariectomized and killed 1, 3, 10, 30, or 60 days after OVX. Catecholamines (CA) were measured by a radioenzymatic isotopic assay. LHRH, LH, and FSH were measured by RIA. CA turnover estimates were obtained after blocking CA synthesis with alpha-methyl-p-tyrosine. Twenty-four hours after OVX, serum FSH rose 3-fold while LH remained unchanged. An abrupt rise in the LHRH content of the ME and MBH (P<0.05) was found, while the LHRH content of the SCH-PO was unaltered. The content of DA in the ME and MBH showed a significant rise at 24 h. A significant increase in DA turnover in the ME was also observed at this time. LH rose slightly 3 days after OVX and increased 7-fold by day 10. The LHRH content of the SCH-PO started to rise by day 3 and reached peak levels by day 10, while in the ME and MBH it declined by day 3 and was significantly lower than D1 levels 10 days after OVX. The DA content of the ME and MBH and the NE content of the ME, MBH, and SCH-PO increased significantly by day 3. NE turnover in the SCH-PO increased significantly by day 3 and stayed elevated at day 10. A similar increment in NE turnover in the ME was observed at day 10. By 30 and 60 days after OVX, serum LH and FSH plateaued, LHRH in the ME and MBH remained significantly lower, SCH-PO LHRH declined to D1 values, and CAs in all areas returned to control levels. The acute negative feedback effect of E2 was evaluated 10 days after OVX by injecting 20 microg E2 benzoate 3 h before sacrifice. After E2 treatment, LH was lowered by 75%, but FSH was unchanged. A significant reduction to D1 levels of the contents of both LHRH and NE in the SCH-PO and a significant decrease in NE turnover in the SCH-PO and a significant decrease in NE turnover in the SCH-PO and ME were observed. LHRH levels in other regions were not significantly altered, although levels were already low before estrogen. Surprisingly, DA and NE turnover in the MBH, which had not changed after OVX, were significantly increased after E2 treatment. DA turnover in the SCH-PO was decreased after E2. These results show a temporal relationship between gonadotropin release and LHRH and CA content and turnover in different brain areas, and indicate that the acute negative feedback effect of E2 is mediated, at least in part, through changes in LHRH and NE metabolism in the SCH-PO and ME regions. These results also stress the necessity of studying smaller hypothalamic regions, since changes in the opposite direction in neighboring areas were observed after either OVX or E2 benzoate treatment...