title: Estradiol impairs hypothalamic molecular responses to hypoglycemia.
abstract: In rats and humans estradiol attenuates neuroendocrine responses to hypoglycemia. Since neuroendocrine responses to hypoglycemia are mediated by hypothalamic neurons, we assessed if estradiol attenuates hypoglycemia-induced gene expression in the hypothalamus in female ovariectomized mice. As expected, estradiol-implanted ovariectomized mice exhibited increased plasma estradiol, increased uterine weight, decreased body weight, decreased visceral adiposity, and enhanced glucose tolerance with decreased plasma insulin. Estradiol-implanted mice exhibited attenuated hypoglycemia-induced gene expression of both glucose transporter 1 (Glut1) and inhibitor of kappa beta signaling (IkappaB) in the hypothalamus but not in the liver. Estradiol also attenuated hypoglycemia-induced plasma glucagon, pituitary proopiomelanocortin (POMC), and adrenal c-fos, consistent with impaired counterregulatory responses to hypoglycemia. In addition, estradiol inhibited hypothalamic expression of carnitine palmitoyltransferase (CPT1a and CPT1c) and pyruvate dehydrogenase kinase 4 (PDK4), effects that would be expected to enhance the accumulation of long-chain fatty acids and glycolysis. Taken together, these findings suggest hypothalamic mechanisms mediating attenuation of hypoglycemia-induced neuroendocrine responses.
authors.affiliation: Fishberg Department of Neuroscience, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Cheng
authors.forename: Fumiko
authors.initials: F
authors.lastname: Isoda
authors.forename: Charles V
authors.initials: CV
authors.lastname: Mobbs
mesh_terms: D050154:Adiposity / Q000187:drug effects; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D004967:Estrogens / Q000097:blood / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005951:Glucose Tolerance Test; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D007003:Hypoglycemia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism*; D020672:I-kappa B Proteins / Q000378:metabolism; D007328:Insulin / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size; D010052:Ovariectomy; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D011897:Random Allocation; D014599:Uterus / Q000187:drug effects / Q000473:pathology
chemical_list: D004967:Estrogens; D051272:Glucose Transporter Type 1; D020672:I-kappa B Proteins; D007328:Insulin; C000631432:PDK4 protein, human; C000631439:Pdk4 protein, mouse; C000631440:Pdk4 protein, rat; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; C495678:Slc2a1 protein, mouse; D004958:Estradiol; D002334:Carnitine O-Palmitoyltransferase; D017346:Protein Serine-Threonine Kinases