Abstract
Insulin can act within the brain to stimulate ovine luteinizing hormone (LH) secretion, but insulin-induced hypoglycaemia inhibits LH via unknown brain sites, possibly involving corticotrophin-releasing factor (CRF), Castrate male sheep, with (E+) or without (E-) subcutaneous oestradiol 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 dose 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 was 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 by 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 paraventricular nucleus (PVN), but not in any other hypothalamic nuclei nor in the hindbrain; and this was linked with increased CRF gene expression in the PVN. Similar c-fos and CRF gene expression was seen in insulin-treated sheep given additional i.v. glucose (20 and 10 mmol, respectively, 40 and 20 min ante mortem), but not in saline-treated controls. Therefore, insulin-induced hypoglycaemia inhibited LH secretion, with oestradiol potentiating the effect, and was associated with gonadal steroid-independent c-fos gene expression and increased CRF gene expression in the PVN, The ovine PVN may be involved in mediating insulin-induced hypoglycaemic inhibition of LH by a mechanism which might involve CRF.
Original language | English |
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Pages (from-to) | 777-783 |
Number of pages | 7 |
Journal | Journal of Neuroendocrinology |
Volume | 10 |
Issue number | 10 |
DOIs | |
Publication status | Published - Oct 1998 |
Keywords
- c-fos
- corticotrophin-releasing factor
- hypoglycaemia
- luteinizing hormone
- sheep
- HYPOGLYCEMIA-INDUCED INHIBITION
- GONADOTROPIN-SECRETION
- RAT HYPOTHALAMUS
- MESSENGER-RNA
- RHESUS-MONKEY
- FACTOR CRF
- GLUCOSE AVAILABILITY
- GROWTH-HORMONE
- LH-SECRETION
- BRAIN-STEM
- sheep
- hypoglycemia-induced inhibition
- gonadotropin-secretion
- rat hypothalamus
- messenger-RNA
- rhesus monkey
- factor CRF
- glucose availability
- growth-hormone
- LH-secretion
- brain-stem