PMID- 30954669 OWN - NLM STAT- MEDLINE DCOM- 20200109 LR - 20200615 IS - 1873-7544 (Electronic) IS - 0306-4522 (Print) IS - 0306-4522 (Linking) VI - 409 DP - 2019 Jun 15 TI - Hindbrain estrogen receptor regulation of ventromedial hypothalamic glycogen metabolism and glucoregulatory transmitter expression in the hypoglycemic male rat. PG - 253-260 LID - S0306-4522(19)30215-5 [pii] LID - 10.1016/j.neuroscience.2019.03.053 [doi] AB - Estrogen receptor-alpha (ERalpha) and -beta (ERbeta) occur in key elements of the brain gluco-homeostatic network in both sexes, including the hindbrain dorsal vagal complex (DVC), but the influence of distinct receptor populations on this critical function is unclear. The ventromedial hypothalamic nucleus (VMN) maintains glucose balance by integrating nutrient, endocrine, and neurochemical cues, including metabolic sensory information supplied by DVC A2 noradrenergic neurons. Current research utilized the selective ERalpha and ERbeta antagonists MPP and PHTPP to characterize effects of DVC ERs on VMN norepinephrine (NE) activity and metabolic neurotransmitter signaling in insulin-induced hypoglycemic (IIH) male rats. Data show that ERbeta inhibits VMN glycogen synthase and stimulates phosphorylase protein expression, while attenuating hypoglycemic augmentation of glycogen content. Furthermore, both ERs attenuate VMN glucose concentrations during IIH. Hypoglycemic up-regulation of nitric oxide (NO) and brain-derived neurotrophic factor (BDNF) signaling was correspondingly driven by ERalpha or -beta, whereas GABA and steroidogenic factor-1 were respectively suppressed independently of ER input or by ERbeta. IIH intensified VMN NE accumulation by ERbeta-dependent mechanisms, but did not alter NE levels in other gluco-regulatory loci. ERbeta amplified the magnitude of insulin-induced decline in blood glucose. Both ERs regulate corticosterone, but not glucagon secretion during IIH and oppose hypoglycemic diminution of circulating free fatty acids. These findings identify distinguishing versus common VMN functions targeted by DVC ERalpha and -beta. Sex differences in hypoglycemic VMN NE accumulation, glycogen metabolism, and transmitter signaling may involve, in part, discrepant regulatory involvement or differential magnitude of impact of these hindbrain ERs. CI - Copyright (c) 2019. Published by Elsevier Ltd. FAU - Ali, Md Haider AU - Ali MH AD - School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, Monroe, LA 71201, United States of America. FAU - Napit, Prabhat R AU - Napit PR AD - School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, Monroe, LA 71201, United States of America. FAU - Mahmood, A S M Hasan AU - Mahmood ASMH AD - School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, Monroe, LA 71201, United States of America. FAU - Bheemanapally, Khaggeswar AU - Bheemanapally K AD - School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, Monroe, LA 71201, United States of America. FAU - Alhamami, Hussain N AU - Alhamami HN AD - School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, Monroe, LA 71201, United States of America. FAU - Uddin, Md Main AU - Uddin MM AD - School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, Monroe, LA 71201, United States of America. FAU - Mandal, Santosh K AU - Mandal SK AD - School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, Monroe, LA 71201, United States of America. FAU - Ibrahim, Mostafa M H AU - Ibrahim MMH AD - School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, Monroe, LA 71201, United States of America. FAU - Briski, K P AU - Briski KP AD - School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, Monroe, LA 71201, United States of America. Electronic address: briski@ulm.edu. LA - eng GR - R01 DK109382/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20190405 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (1,3-bis(4-hydroxyphenyl)-4-methyl-5-(4-(2-piperidinylethoxy)phenol)-1H-pyrazole) RN - 0 (4-(2-phenyl-5,7-bis(trifluoromethyl)pyrazolo(1,5-a)pyrimidin-3-yl)phenol) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Piperidines) RN - 0 (Pyrazoles) RN - 0 (Pyrimidines) RN - 0 (Receptors, Estrogen) RN - 31C4KY9ESH (Nitric Oxide) RN - 9005-79-2 (Glycogen) RN - IY9XDZ35W2 (Glucose) RN - W980KJ009P (Corticosterone) RN - X4W3ENH1CV (Norepinephrine) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/metabolism MH - Corticosterone/metabolism MH - Glucose/*metabolism MH - Glycogen/*metabolism MH - Hypoglycemia/*metabolism MH - Male MH - Nitric Oxide/metabolism MH - Norepinephrine/metabolism MH - Piperidines/pharmacology MH - Pyrazoles/pharmacology MH - Pyrimidines/pharmacology MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, Estrogen/antagonists & inhibitors/*metabolism MH - Rhombencephalon/drug effects/*metabolism MH - Ventromedial Hypothalamic Nucleus/drug effects/*metabolism PMC - PMC6594372 MID - NIHMS1034096 OTO - NOTNLM OT - MPP OT - PHTPP OT - glutamate decarboxylase OT - glycogen OT - nitric oxide synthase OT - norepinephrine EDAT- 2019/04/08 06:00 MHDA- 2020/01/10 06:00 PMCR- 2020/06/15 CRDT- 2019/04/08 06:00 PHST- 2018/10/16 00:00 [received] PHST- 2019/03/25 00:00 [revised] PHST- 2019/03/26 00:00 [accepted] PHST- 2019/04/08 06:00 [pubmed] PHST- 2020/01/10 06:00 [medline] PHST- 2019/04/08 06:00 [entrez] PHST- 2020/06/15 00:00 [pmc-release] AID - S0306-4522(19)30215-5 [pii] AID - 10.1016/j.neuroscience.2019.03.053 [doi] PST - ppublish SO - Neuroscience. 2019 Jun 15;409:253-260. doi: 10.1016/j.neuroscience.2019.03.053. Epub 2019 Apr 5.