PMID- 37280378
OWN - NLM
STAT- MEDLINE
DCOM- 20230703
LR  - 20240118
IS  - 1365-2826 (Electronic)
IS  - 0953-8194 (Linking)
VI  - 35
IP  - 6
DP  - 2023 Jun
TI  - Defining potential targets of prenatal androgen excess: Expression analysis of 
      androgen receptor on hypothalamic neurons in the fetal female mouse brain.
PG  - e13302
LID - 10.1111/jne.13302 [doi]
AB  - Polycystic ovary syndrome (PCOS) is a female endocrine disorder that is 
      associated with prenatal exposure to excess androgens. In prenatally androgenized 
      (PNA) mice that model PCOS, GABAergic neural transmission to and innervation of 
      GnRH neurons is increased. Evidence suggests that elevated GABAergic innervation 
      originates in the arcuate nucleus (ARC). We hypothesized that GABA-GnRH circuit 
      abnormalities are a direct consequence of PNA, resulting from DHT binding to 
      androgen receptor (AR) in the prenatal brain. However, whether prenatal ARC 
      neurons express AR at the time of PNA treatment is presently unknown. We used 
      RNAScope in situ hybridization to localize AR mRNA (Ar)-expressing cells in 
      healthy gestational day (GD) 17.5 female mouse brains and to assess coexpression 
      levels in specific neuronal phenotypes. Our study revealed that less than 10% of 
      ARC GABA cells expressed Ar. In contrast, we found that ARC kisspeptin neurons, 
      critical regulators of GnRH neurons, were highly colocalized with Ar. 
      Approximately 75% of ARC Kiss1-expressing cells also expressed Ar at GD17.5, 
      suggesting that ARC kisspeptin neurons are potential targets of PNA. 
      Investigating other neuronal populations in the ARC we found that ~50% of 
      pro-opiomelanocortin (Pomc) cells, 22% of tyrosine hydroxylase (Th) cells, 8% of 
      agouti-related protein (Agrp) cells and 8% of somatostatin (Sst) cells express 
      Ar. Lastly, RNAscope in coronal sections showed Ar expression in the medial 
      preoptic area (mPOA), and the ventral part of the lateral septum (vLS). These 
      Ar-expressing regions were highly GABAergic, and 22% of GABA cells in the mPOA 
      and 25% of GABA cells in the vLS also expressed Ar. Our findings identify 
      specific neuronal phenotypes in the ARC, mPOA, and vLS that are androgen 
      sensitive in late gestation. PNA-induced functional changes in these neurons may 
      be related to the development of impaired central mechanisms associated with 
      PCOS-like features.
CI  - (c) 2023 The Authors. Journal of Neuroendocrinology published by John Wiley & Sons 
      Ltd on behalf of British Society for Neuroendocrinology.
FAU - Watanabe, Yugo
AU  - Watanabe Y
AUID- ORCID: 0000-0001-6920-5360
AD  - Centre for Neuroendocrinology, Department of Anatomy, University of Otago School 
      of Biomedical Sciences, Dunedin, New Zealand.
FAU - Fisher, Lorryn
AU  - Fisher L
AD  - Centre for Neuroendocrinology, Department of Anatomy, University of Otago School 
      of Biomedical Sciences, Dunedin, New Zealand.
FAU - Campbell, Rebecca E
AU  - Campbell RE
AUID- ORCID: 0000-0002-0309-532X
AD  - Centre for Neuroendocrinology, Department of Physiology, University of Otago 
      School of Biomedical Sciences, Dunedin, New Zealand.
FAU - Jasoni, Christine L
AU  - Jasoni CL
AUID- ORCID: 0000-0002-2945-8301
AD  - Centre for Neuroendocrinology, Department of Anatomy, University of Otago School 
      of Biomedical Sciences, Dunedin, New Zealand.
LA  - eng
GR  - 18-671/Health Research Council of New Zealand/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230606
PL  - United States
TA  - J Neuroendocrinol
JT  - Journal of neuroendocrinology
JID - 8913461
RN  - 0 (Androgens)
RN  - 0 (Receptors, Androgen)
RN  - 0 (Kisspeptins)
RN  - 33515-09-2 (Gonadotropin-Releasing Hormone)
SB  - IM
MH  - Humans
MH  - Mice
MH  - Female
MH  - Pregnancy
MH  - Animals
MH  - *Androgens/metabolism
MH  - Receptors, Androgen/metabolism
MH  - Kisspeptins/metabolism
MH  - Arcuate Nucleus of Hypothalamus/metabolism
MH  - Gonadotropin-Releasing Hormone/metabolism
MH  - GABAergic Neurons/physiology
MH  - *Polycystic Ovary Syndrome
MH  - Brain/metabolism
MH  - Virilism/metabolism
OTO - NOTNLM
OT  - GABA
OT  - androgen receptor
OT  - kisspeptin
OT  - polycystic ovary syndrome
OT  - prenatal androgen exposure
EDAT- 2023/06/07 01:07
MHDA- 2023/07/03 06:42
CRDT- 2023/06/06 23:27
PHST- 2023/04/05 00:00 [revised]
PHST- 2023/01/23 00:00 [received]
PHST- 2023/04/27 00:00 [accepted]
PHST- 2023/07/03 06:42 [medline]
PHST- 2023/06/07 01:07 [pubmed]
PHST- 2023/06/06 23:27 [entrez]
AID - 10.1111/jne.13302 [doi]
PST - ppublish
SO  - J Neuroendocrinol. 2023 Jun;35(6):e13302. doi: 10.1111/jne.13302. Epub 2023 Jun 
      6.