PMID- 27316550
OWN - NLM
STAT- MEDLINE
DCOM- 20170711
LR  - 20181203
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Print)
IS  - 0306-4522 (Linking)
VI  - 331
DP  - 2016 Sep 7
TI  - Hindbrain estrogen receptor-beta antagonism normalizes reproductive and 
      counter-regulatory hormone secretion in hypoglycemic steroid-primed 
      ovariectomized female rats.
PG  - 62-71
LID - S0306-4522(16)30244-5 [pii]
LID - 10.1016/j.neuroscience.2016.06.014 [doi]
AB  - Hindbrain dorsal vagal complex A2 noradrenergic signaling represses the 
      pre-ovulatory luteinizing hormone (LH) surge in response to energy deficiency. 
      Insulin-induced hypoglycemia augments A2 neuron adenosine 
      5'-monophosphate-activated protein kinase (AMPK) activity and estrogen 
      receptor-beta (ERbeta) expression, coincident with LH surge suppression. We 
      hypothesized that ERbeta is critical for hypoglycemia-associated patterns of LH 
      secretion and norepinephrine (NE) activity in key reproduction-relevant forebrain 
      structures. The neural mechanisms responsible for tight coupling of systemic 
      energy balance and procreation remain unclear; here, we investigated whether 
      ERbeta-dependent hindbrain signals also control glucose counter-regulatory responses 
      to hypoglycemia. Gonadal steroid-primed ovariectomized female rats were 
      pretreated by caudal fourth ventricular administration of the ERbeta antagonist 
      4-[2-phenyl-5,7-bis(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-yl]phenol (PHTPP) 
      or vehicle before insulin injection at LH surge onset. Western blot analysis of 
      laser-microdissected A2 neurons revealed hypoglycemic intensification of AMPK 
      activity and dopamine-beta-hydroxylase protein expression; the latter response was 
      attenuated by PHTPP pretreatment. PHTPP regularized LH release, but not preoptic 
      GnRH-I precursor protein expression in insulin-injected rats, and reversed 
      hypoglycemic stimulation of glucagon and corticosterone secretion. Hypoglycemia 
      caused PHTPP-reversible changes in NE and prepro-kisspeptin protein content in 
      the hypothalamic arcuate (ARH), but not anteroventral periventricular nucleus. 
      Results provide novel evidence for ERbeta-dependent caudal hindbrain regulation of 
      LH and counter-regulatory hormone secretion during hypoglycemia. Observed 
      inhibition of LH likely involves mechanisms at the axon terminal that impede GnRH 
      neurotransmission. Data also show that caudal hindbrain ERbeta exerts site-specific 
      control of NE activity in forebrain projection sites during hypoglycemia, 
      including the ARH where prepro-kisspeptin may be a target of that signaling.
CI  - Copyright (c) 2016 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Briski, Karen P
AU  - Briski KP
AD  - Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of 
      Louisiana at Monroe, Monroe, LA 71291, United States. Electronic address: 
      briski@ulm.edu.
FAU - Shrestha, Prem K
AU  - Shrestha PK
AD  - Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of 
      Louisiana at Monroe, Monroe, LA 71291, United States.
LA  - eng
GR  - R21 HD083389/HD/NICHD NIH HHS/United States
PT  - Journal Article
DEP - 20160615
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (4-(2-phenyl-5,7-bis(trifluoromethyl)pyrazolo(1,5-a)pyrimidin-3-yl)phenol)
RN  - 0 (Estrogen Receptor Modulators)
RN  - 0 (Estrogen Receptor beta)
RN  - 0 (Pyrazoles)
RN  - 0 (Pyrimidines)
RN  - 33515-09-2 (Gonadotropin-Releasing Hormone)
RN  - 9002-67-9 (Luteinizing Hormone)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Animals
MH  - Estrogen Receptor Modulators/pharmacology
MH  - Estrogen Receptor beta/*antagonists & inhibitors/*metabolism
MH  - Female
MH  - Gonadotropin-Releasing Hormone/metabolism
MH  - Hypoglycemia/*metabolism
MH  - Luteinizing Hormone/*metabolism
MH  - Neurons/drug effects/metabolism
MH  - Norepinephrine/*metabolism
MH  - Ovariectomy
MH  - Pyrazoles/pharmacology
MH  - Pyrimidines/pharmacology
MH  - Rats, Sprague-Dawley
MH  - Rhombencephalon/*drug effects/metabolism
PMC - PMC4956474
MID - NIHMS800699
OTO - NOTNLM
OT  - A2 noradrenergic neurons
OT  - GnRH
OT  - LH
OT  - PHTPP
OT  - arcuate nucleus
OT  - estrogen receptor-beta
EDAT- 2016/06/19 06:00
MHDA- 2017/07/14 06:00
PMCR- 2017/09/07
CRDT- 2016/06/19 06:00
PHST- 2016/03/09 00:00 [received]
PHST- 2016/06/08 00:00 [revised]
PHST- 2016/06/09 00:00 [accepted]
PHST- 2016/06/19 06:00 [entrez]
PHST- 2016/06/19 06:00 [pubmed]
PHST- 2017/07/14 06:00 [medline]
PHST- 2017/09/07 00:00 [pmc-release]
AID - S0306-4522(16)30244-5 [pii]
AID - 10.1016/j.neuroscience.2016.06.014 [doi]
PST - ppublish
SO  - Neuroscience. 2016 Sep 7;331:62-71. doi: 10.1016/j.neuroscience.2016.06.014. Epub 
      2016 Jun 15.