INHIBITION OF LUTEINIZING-HORMONE SECRETION AND EXPRESSION OF C-FOS AND CORTICOTROPIN-RELEASING FACTOR GENES IN THE PARAVENTRICULAR NUCLEUSDURING INSULIN-INDUCED HYPOGLYCEMIA IN SHEEP

Insulin can act within the brain to stimulate ovine luteinizing hormon e (LH) secretion, but insulin-induced hypoglycaemia inhibits LH via un known brain sites, possibly involving corticotrophin-releasing factor (CRF), Castrate male sheep, with (E+) or without (E-) subcutaneous oes tradiol implants, were blood sampled every 12 min for 8 h. Insulin (0. 25 or 0.5 IU/kg) was injected at 4 h via the carotid artery or jugular vein, All treatments reduced LH output with no differences between do se rate nor route of administration, but sensitivity was greater in E than E-sheep. There was no evidence for an effect of insulin on LH 0- 1 h postinjection; however, 1-3 h after insulin, when hypoglycaemia wa s established, LH pulses were inhibited in both E+ and E- sheep (P < 0 .001). Additional intravenous (i.v.) glucose injections given 1 h (20 mmol) and 2 h (10 mmol) after insulin (0.5 IU/kg) were each followed b y an LH pulse within 30 min (75% response in both E+ and E- sheep). In a separate experiment, sheep were killed 2 h after i.v. insulin (0.5 IU/kg) or saline. In-situ hybridization revealed c-fos mRNA in the par aventricular nucleus (PVN), but not in any other hypothalamic nuclei n or in the hindbrain; and this was linked with increased CRF gene expre ssion in the PVN. Similar c-fos and CRF gene expression was seen in in sulin-treated sheep given additional i.v. glucose (20 and 10 mmol, res pectively, 40 and 20 min ante mortem), but not in saline-treated contr ols. Therefore, insulin-induced hypoglycaemia inhibited LH secretion, with oestradiol potentiating the effect, and was associated with gonad al steroid-independent c-fos gene expression and increased CRF gene ex pression in the PVN, The ovine PVN may be involved in mediating insuli n-induced hypoglycaemic inhibition of LH by a mechanism which might in volve CRF.