PMID- 32067028
OWN - NLM
STAT- MEDLINE
DCOM- 20200805
LR  - 20240423
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 161
IP  - 3
DP  - 2020 Mar 1
TI  - Evidence that Nitric Oxide Is Critical for LH Surge Generation in Female Sheep.
LID - 10.1210/endocr/bqaa010 [doi]
LID - bqaa010
AB  - Elevated and sustained estradiol concentrations cause a gonadotropin-releasing 
      hormone (GnRH) and luteinizing hormone (LH) surge that is necessary for 
      ovulation. In sheep, several different neural systems have been implicated in 
      this stimulatory action of estradiol and this study focused on somatostatin (SST) 
      neurons in the ventral lateral region of the ventral medial nucleus (vlVMN) which 
      express c-Fos during the surge. First, we determined if increased activity of SST 
      neurons could be related to elevated GnRH secretion by assessing SST synapses 
      onto GnRH neurons and neurons coexpressing kisspeptin, neurokinin B, dynorphin 
      (KNDy). We found that the percentage of preoptic area GnRH neurons that receive 
      SST input increased during the surge compared with other phases of the cycle. 
      However, since SST is generally inhibitory, and pharmacological manipulation of 
      SST signaling did not alter the LH surge in sheep, we hypothesized that nitric 
      oxide (NO) was also produced by these neurons to account for their activation 
      during the surge. In support of this hypothesis we found that (1) the majority of 
      SST cells in the vlVMN (>80%) contained neuronal nitric oxide synthase (nNOS); 
      (2) the expression of c-Fos in dual-labeled SST-nNOS cells, but not in 
      single-labeled cells, increased during the surge compared with other phases of 
      the cycle; and (3) intracerebroventricular (ICV) infusion of the nitric oxide 
      synthase inhibitor, N(G)-nitro-L-arginine methyl ester, completely blocked the 
      estrogen-induced LH surge. These data support the hypothesis that the population 
      of SST-nNOS cells in the vlVMN are a source of NO that is critical for the LH 
      surge, and we propose that they are an important site of estradiol positive 
      feedback in sheep.
CI  - (c) Endocrine Society 2020. All rights reserved. For permissions, please e-mail: 
      journals.permissions@oup.com.
FAU - McCosh, Richard B
AU  - McCosh RB
AD  - Department of Physiology and Pharmacology, West Virginia University Health 
      Science Center, Morgantown, West Virginia.
FAU - Lopez, Justin A
AU  - Lopez JA
AD  - Department of Physiology and Pharmacology, West Virginia University Health 
      Science Center, Morgantown, West Virginia.
FAU - Szeligo, Brett M
AU  - Szeligo BM
AD  - Department of Physiology and Pharmacology, West Virginia University Health 
      Science Center, Morgantown, West Virginia.
FAU - Bedenbaugh, Michelle N
AU  - Bedenbaugh MN
AD  - Department of Physiology and Pharmacology, West Virginia University Health 
      Science Center, Morgantown, West Virginia.
FAU - Hileman, Stanley M
AU  - Hileman SM
AD  - Department of Physiology and Pharmacology, West Virginia University Health 
      Science Center, Morgantown, West Virginia.
FAU - Coolen, Lique M
AU  - Coolen LM
AD  - Brain Health Research Institute, Kent State University, Kent, Ohio.
AD  - Department of Biological Sciences, Kent State University, Kent, Ohio.
FAU - Lehman, Michael N
AU  - Lehman MN
AD  - Brain Health Research Institute, Kent State University, Kent, Ohio.
FAU - Goodman, Robert L
AU  - Goodman RL
AD  - Department of Physiology and Pharmacology, West Virginia University Health 
      Science Center, Morgantown, West Virginia.
LA  - eng
GR  - R01 HD082135/HD/NICHD NIH HHS/United States
GR  - R01 HD039916/HD/NICHD NIH HHS/United States
GR  - P30 RR032138/RR/NCRR NIH HHS/United States
GR  - P20 GM103434/GM/NIGMS NIH HHS/United States
GR  - U54 GM104942/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 51110-01-1 (Somatostatin)
RN  - 9002-67-9 (Luteinizing Hormone)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type I)
SB  - IM
MH  - Animals
MH  - Female
MH  - Luteinizing Hormone/*blood
MH  - Nitric Oxide/*metabolism
MH  - Nitric Oxide Synthase Type I/metabolism
MH  - *Ovulation
MH  - Sheep/*blood
MH  - Somatostatin/metabolism
MH  - Ventromedial Hypothalamic Nucleus/*enzymology
PMC - PMC7060766
OTO - NOTNLM
OT  - L-NAME
OT  - luteinizing hormone
OT  - neuronal nitric oxide synthase
OT  - somatostatin
EDAT- 2020/02/19 06:00
MHDA- 2020/08/06 06:00
PMCR- 2021/02/18
CRDT- 2020/02/19 06:00
PHST- 2019/12/12 00:00 [received]
PHST- 2020/01/31 00:00 [accepted]
PHST- 2020/02/19 06:00 [pubmed]
PHST- 2020/08/06 06:00 [medline]
PHST- 2020/02/19 06:00 [entrez]
PHST- 2021/02/18 00:00 [pmc-release]
AID - 5739620 [pii]
AID - bqaa010 [pii]
AID - 10.1210/endocr/bqaa010 [doi]
PST - ppublish
SO  - Endocrinology. 2020 Mar 1;161(3):bqaa010. doi: 10.1210/endocr/bqaa010.