PMID- 31415088
OWN - NLM
STAT- MEDLINE
DCOM- 20191223
LR  - 20231213
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 160
IP  - 11
DP  - 2019 Nov 1
TI  - Prenatal Testosterone Exposure Alters GABAergic Synaptic Inputs to GnRH and KNDy 
      Neurons in a Sheep Model of Polycystic Ovarian Syndrome.
PG  - 2529-2542
LID - 10.1210/en.2019-00137 [doi]
AB  - Prenatal testosterone (T)-treated female sheep display reproductive deficits 
      similar to women with polycystic ovarian syndrome (PCOS), including an increase 
      in LH pulse frequency due to actions of the central GnRH pulse generator. In this 
      study, we used multiple-label immunocytochemistry to investigate the possibility 
      of changes in the gamma-aminobutyric acid (GABA) neurotransmitter system at two key 
      components of the GnRH pulse generator in prenatal T-treated sheep: 
      kisspeptin/neurokinin B/dynorphin (KNDy) neurons of the arcuate nucleus, and GnRH 
      neurons in the preoptic area (POA) and mediobasal hypothalamus (MBH). We observed 
      a significant decrease and increase, respectively, in the number of GABAergic 
      synapses onto POA and MBH GnRH neurons in prenatal T-treated ewes; additionally, 
      there was a significant increase in the number of GABAergic inputs onto KNDy 
      neurons. To determine the actions of GABA on GnRH and KNDy neurons, we examined 
      colocalization with the chloride transporters NKCC1 and KCC2, which indicate 
      stimulatory or inhibitory activation of neurons by GABA, respectively. Most GnRH 
      neurons in both POA and MBH colocalized NKCC1 cotransporter whereas none 
      contained the KCC2 cotransporter. Most KNDy neurons colocalized either NKCC1 or 
      KCC2, and 28% of the KNDy population contained NKCC1 alone. Therefore, we suggest 
      that, as in the mouse, GABA in the sheep is stimulatory to GnRH neurons, as well 
      as to a subset of KNDy neurons. Increased numbers of stimulatory GABAergic inputs 
      to both MBH GnRH and KNDy neurons in prenatal T-treated animals may contribute to 
      alterations in steroid feedback control and increased GnRH/LH pulse frequency 
      seen in this animal model of PCOS.
CI  - Copyright (c) 2019 Endocrine Society.
FAU - Porter, Danielle T
AU  - Porter DT
AD  - Graduate Program in Neuroscience, Department of Neurobiology and Anatomical 
      Sciences, University of Mississippi Medical Center, Jackson, Mississippi.
FAU - Moore, Aleisha M
AU  - Moore AM
AD  - Brain Health Research Institute, Kent State University, Kent, Ohio.
AD  - Department of Biological Sciences, Kent State University, Kent, Ohio.
FAU - Cobern, Jade A
AU  - Cobern JA
AD  - Graduate Program in Neuroscience, Department of Neurobiology and Anatomical 
      Sciences, University of Mississippi Medical Center, Jackson, Mississippi.
FAU - Padmanabhan, Vasantha
AU  - Padmanabhan V
AD  - Department of Pediatrics, University of Michigan, Ann Arbor, Michigan.
FAU - Goodman, Robert L
AU  - Goodman RL
AD  - Department of Physiology and Pharmacology, West Virginia University, Morgantown, 
      West Virginia.
FAU - Coolen, Lique M
AU  - Coolen LM
AD  - Graduate Program in Neuroscience, Department of Neurobiology and Anatomical 
      Sciences, University of Mississippi Medical Center, Jackson, Mississippi.
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  - Graduate Program in Neuroscience, Department of Neurobiology and Anatomical 
      Sciences, University of Mississippi Medical Center, Jackson, Mississippi.
AD  - Brain Health Research Institute, Kent State University, Kent, Ohio.
AD  - Department of Biological Sciences, Kent State University, Kent, Ohio.
LA  - eng
GR  - P01 HD044232/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Kisspeptins)
RN  - 0 (Solute Carrier Family 12, Member 2)
RN  - 0 (Symporters)
RN  - 33515-09-2 (Gonadotropin-Releasing Hormone)
RN  - 3XMK78S47O (Testosterone)
RN  - 74913-18-1 (Dynorphins)
RN  - 86933-75-7 (Neurokinin B)
SB  - IM
MH  - Animals
MH  - Arcuate Nucleus of Hypothalamus/metabolism/*physiopathology
MH  - Disease Models, Animal
MH  - Dynorphins/metabolism
MH  - Female
MH  - GABAergic Neurons/*physiology
MH  - Gonadotropin-Releasing Hormone/*metabolism
MH  - Kisspeptins/metabolism
MH  - Neurokinin B/metabolism
MH  - Polycystic Ovary Syndrome/metabolism/*physiopathology
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects
MH  - Preoptic Area/metabolism/*physiopathology
MH  - Sheep
MH  - Solute Carrier Family 12, Member 2/metabolism
MH  - Symporters/metabolism
MH  - Testosterone
MH  - K Cl- Cotransporters
PMC - PMC6779074
EDAT- 2019/08/16 06:00
MHDA- 2019/12/24 06:00
PMCR- 2020/08/15
CRDT- 2019/08/16 06:00
PHST- 2019/02/19 00:00 [received]
PHST- 2019/08/05 00:00 [accepted]
PHST- 2019/08/16 06:00 [pubmed]
PHST- 2019/12/24 06:00 [medline]
PHST- 2019/08/16 06:00 [entrez]
PHST- 2020/08/15 00:00 [pmc-release]
AID - 5550195 [pii]
AID - 201900137 [pii]
AID - 10.1210/en.2019-00137 [doi]
PST - ppublish
SO  - Endocrinology. 2019 Nov 1;160(11):2529-2542. doi: 10.1210/en.2019-00137.