PMID- 26061725
OWN - NLM
STAT- MEDLINE
DCOM- 20151117
LR  - 20220311
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 156
IP  - 9
DP  - 2015 Sep
TI  - Prenatal Testosterone Treatment Leads to Changes in the Morphology of KNDy 
      Neurons, Their Inputs, and Projections to GnRH Cells in Female Sheep.
PG  - 3277-91
LID - 10.1210/en.2014-1609 [doi]
AB  - Prenatal testosterone (T)-treated ewes display a constellation of reproductive 
      defects that closely mirror those seen in PCOS women, including altered hormonal 
      feedback control of GnRH. Kisspeptin/neurokinin B/dynorphin (KNDy) neurons of the 
      arcuate nucleus (ARC) play a key role in steroid feedback control of GnRH 
      secretion, and prenatal T treatment in sheep causes an imbalance of KNDy peptide 
      expression within the ARC. In the present study, we tested the hypothesis that 
      prenatal T exposure, in addition to altering KNDy peptides, leads to changes in 
      the morphology and synaptic inputs of this population, kisspeptin cells of the 
      preoptic area (POA), and GnRH cells. Prenatal T treatment significantly increased 
      the size of KNDy cell somas, whereas POA kisspeptin, GnRH, agouti-related 
      peptide, and proopiomelanocortin neurons were each unchanged in size. Prenatal T 
      treatment also significantly reduced the total number of synaptic inputs onto 
      KNDy neurons and POA kisspeptin neurons; for KNDy neurons, the decrease was 
      partly due to a decrease in KNDy-KNDy synapses, whereas KNDy inputs to POA 
      kisspeptin cells were unaltered. Finally, prenatal T reduced the total number of 
      inputs to GnRH cells in both the POA and medial basal hypothalamus, and this 
      change was in part due to a decreased number of inputs from KNDy neurons. The 
      hypertrophy of KNDy cells in prenatal T sheep resembles that seen in ARC 
      kisspeptin cells of postmenopausal women, and together with changes in their 
      synaptic inputs and projections to GnRH neurons, may contribute to defects in 
      steroidal control of GnRH observed in this animal model.
FAU - Cernea, Maria
AU  - Cernea M
AD  - Department of Neurobiology and Anatomical Sciences (M.C., L.M.C., M.N.L.), The 
      University of Mississippi Medical Center, Jackson, Mississippi 39232; Department 
      of Obstetrics and Gynecology, Pediatrics, and Reproductive Sciences Program 
      (V.P.), University of Michigan, Ann Arbor, Michigan 48109; and Department of 
      Physiology and Pharmacology (R.L.G.), West Virginia University, Morgantown, West 
      Virginia 26506.
FAU - Padmanabhan, Vasantha
AU  - Padmanabhan V
AD  - Department of Neurobiology and Anatomical Sciences (M.C., L.M.C., M.N.L.), The 
      University of Mississippi Medical Center, Jackson, Mississippi 39232; Department 
      of Obstetrics and Gynecology, Pediatrics, and Reproductive Sciences Program 
      (V.P.), University of Michigan, Ann Arbor, Michigan 48109; and Department of 
      Physiology and Pharmacology (R.L.G.), West Virginia University, Morgantown, West 
      Virginia 26506.
FAU - Goodman, Robert L
AU  - Goodman RL
AD  - Department of Neurobiology and Anatomical Sciences (M.C., L.M.C., M.N.L.), The 
      University of Mississippi Medical Center, Jackson, Mississippi 39232; Department 
      of Obstetrics and Gynecology, Pediatrics, and Reproductive Sciences Program 
      (V.P.), University of Michigan, Ann Arbor, Michigan 48109; and Department of 
      Physiology and Pharmacology (R.L.G.), West Virginia University, Morgantown, West 
      Virginia 26506.
FAU - Coolen, Lique M
AU  - Coolen LM
AD  - Department of Neurobiology and Anatomical Sciences (M.C., L.M.C., M.N.L.), The 
      University of Mississippi Medical Center, Jackson, Mississippi 39232; Department 
      of Obstetrics and Gynecology, Pediatrics, and Reproductive Sciences Program 
      (V.P.), University of Michigan, Ann Arbor, Michigan 48109; and Department of 
      Physiology and Pharmacology (R.L.G.), West Virginia University, Morgantown, West 
      Virginia 26506.
FAU - Lehman, Michael N
AU  - Lehman MN
AD  - Department of Neurobiology and Anatomical Sciences (M.C., L.M.C., M.N.L.), The 
      University of Mississippi Medical Center, Jackson, Mississippi 39232; Department 
      of Obstetrics and Gynecology, Pediatrics, and Reproductive Sciences Program 
      (V.P.), University of Michigan, Ann Arbor, Michigan 48109; and Department of 
      Physiology and Pharmacology (R.L.G.), West Virginia University, Morgantown, West 
      Virginia 26506.
LA  - eng
GR  - P01 HD044232/HD/NICHD NIH HHS/United States
GR  - P30 DK020572/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20150610
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Kisspeptins)
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/*cytology
MH  - Disease Models, Animal
MH  - Dynorphins
MH  - Female
MH  - Gonadotropin-Releasing Hormone
MH  - Kisspeptins
MH  - Neurokinin B
MH  - Neurons/*cytology
MH  - Polycystic Ovary Syndrome/etiology
MH  - Pregnancy
MH  - *Prenatal Exposure Delayed Effects
MH  - Preoptic Area/cytology
MH  - Sheep
MH  - *Testosterone
PMC - PMC4541615
EDAT- 2015/06/11 06:00
MHDA- 2015/11/18 06:00
PMCR- 2016/09/01
CRDT- 2015/06/11 06:00
PHST- 2015/06/11 06:00 [entrez]
PHST- 2015/06/11 06:00 [pubmed]
PHST- 2015/11/18 06:00 [medline]
PHST- 2016/09/01 00:00 [pmc-release]
AID - EN-14-1609 [pii]
AID - 10.1210/en.2014-1609 [doi]
PST - ppublish
SO  - Endocrinology. 2015 Sep;156(9):3277-91. doi: 10.1210/en.2014-1609. Epub 2015 Jun 
      10.