Inhibition of luteinizing hormone secretion and expression of c-fos and corticotrophin-releasing factor genes in the paraventricular nucleus during insulin-induced hypoglycaemia in sheep

Clare Lesley Adam, P.A. Findlay

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33 Citations (Scopus)

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 languageEnglish
Pages (from-to)777-783
Number of pages7
JournalJournal of Neuroendocrinology
Volume10
Issue number10
DOIs
Publication statusPublished - 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

Cite this

@article{5479ebc757194cf994035080be5ceda9,
title = "Inhibition of luteinizing hormone secretion and expression of c-fos and corticotrophin-releasing factor genes in the paraventricular nucleus during insulin-induced hypoglycaemia in sheep",
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.",
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",
author = "Adam, {Clare Lesley} and P.A. Findlay",
year = "1998",
month = "10",
doi = "10.1046/j.1365-2826.1998.00263.x",
language = "English",
volume = "10",
pages = "777--783",
journal = "Journal of Neuroendocrinology",
issn = "0953-8194",
publisher = "Wiley-Blackwell",
number = "10",

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TY - JOUR

T1 - Inhibition of luteinizing hormone secretion and expression of c-fos and corticotrophin-releasing factor genes in the paraventricular nucleus during insulin-induced hypoglycaemia in sheep

AU - Adam, Clare Lesley

AU - Findlay, P.A.

PY - 1998/10

Y1 - 1998/10

N2 - 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.

AB - 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.

KW - c-fos

KW - corticotrophin-releasing factor

KW - hypoglycaemia

KW - luteinizing hormone

KW - sheep

KW - HYPOGLYCEMIA-INDUCED INHIBITION

KW - GONADOTROPIN-SECRETION

KW - RAT HYPOTHALAMUS

KW - MESSENGER-RNA

KW - RHESUS-MONKEY

KW - FACTOR CRF

KW - GLUCOSE AVAILABILITY

KW - GROWTH-HORMONE

KW - LH-SECRETION

KW - BRAIN-STEM

KW - sheep

KW - hypoglycemia-induced inhibition

KW - gonadotropin-secretion

KW - rat hypothalamus

KW - messenger-RNA

KW - rhesus monkey

KW - factor CRF

KW - glucose availability

KW - growth-hormone

KW - LH-secretion

KW - brain-stem

U2 - 10.1046/j.1365-2826.1998.00263.x

DO - 10.1046/j.1365-2826.1998.00263.x

M3 - Article

VL - 10

SP - 777

EP - 783

JO - Journal of Neuroendocrinology

JF - Journal of Neuroendocrinology

SN - 0953-8194

IS - 10

ER -