Co-expression of c-Fos with oestradiol receptor α or somatostatin in the arcuate nucleus, ventromedial nucleus and medial preoptic area in the follicular phase of intact ewes: alteration after insulin-induced hypoglycaemia.
The aim of this study was to investigate how acute insulin-induced hypoglycaemia (IIH) alters the activity of cells containing oestradiol receptor α (ERα) or somatostatin (SST) in the arcuate nucleus (ARC) and ventromedial nucleus (VMN), and ERα cells in the medial preoptic area (mPOA) of intact ewes. Follicular phases were synchronized with progesterone vaginal pessaries. Control animals were killed at 0 h or 31 h (n = 5 and 6, respectively) after progesterone withdrawal (PW; time zero). At 28 h, five other animals received insulin (INS; 4 iu/kg) and were subsequently killed at 31 h. Hypothalamic sections were immunostained for ERα or SST each with c-Fos, a marker of neuronal transcriptional activation. Insulin did not alter the percentage of activated ERα cells in the ARC; however, it appeared visually that two insulin-treated animals (INS responders, with no LH surge) had an increase in the VMN (from 32 to 78%) and a decrease in the mPOA (from 40 to 12%) compared to no increase in the two INS non-responders (with an LH surge). The percentage of activated SST cells in the ARC was greater in all four insulin-treated animals (from 10 to 60%), whereas it was visually estimated that activated SST cells in the VMN increased only in the two insulin responders (from 10 to 70%). From these results, we suggest that IIH stimulates SST activation in the ARC as part of the glucose-sensing mechanism but ERα activation is unaffected in this region. We present evidence to support a hypothesis that disruption of the GnRH/LH surge may occur in insulin responders via a mechanism that involves, at least in part, SST cell activation in the VMN along with decreased ERα cell activation in the mPOA.
School of Veterinary Science, University of Liverpool, Leahurst Campus, Neston, Wirral, UK.
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Fergani
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Routly
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Jones
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Pickavance
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Smith
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Dobson
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000737:chemistry; D001786:Blood Glucose / Q000032:analysis; D004958:Estradiol / Q000097:blood; D047628:Estrogen Receptor alpha / Q000032:analysis*; D005260:Female; D005498:Follicular Phase / Q000378:metabolism; D015870:Gene Expression; D006854:Hydrocortisone / Q000097:blood; D007031:Hypothalamus / Q000737:chemistry*; D007328:Insulin / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000097:blood; D011301:Preoptic Area / Q000737:chemistry; D011374:Progesterone / Q000097:blood; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis*; D012756:Sheep / Q000378:metabolism*; D013004:Somatostatin / Q000032:analysis*; D014697:Ventromedial Hypothalamic Nucleus / Q000737:chemistry
D001786:Blood Glucose; D047628:Estrogen Receptor alpha; D007328:Insulin; D016760:Proto-Oncogene Proteins c-fos; D011374:Progesterone; D004958:Estradiol; D013004:Somatostatin; D007986:Luteinizing Hormone; D006854:Hydrocortisone