Prenatal androgenization causes expression changes of progesterone and androgen receptor mRNAs in the arcuate nucleus of female mice across development.
Animals
Animals, Newborn
Arcuate Nucleus of Hypothalamus
/ growth & development
Embryo, Mammalian
Female
Gene Expression Regulation, Developmental
Growth and Development
/ genetics
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Pregnancy
Prenatal Exposure Delayed Effects
/ genetics
RNA, Messenger
/ genetics
Receptors, Androgen
/ genetics
Receptors, Progesterone
/ genetics
Virilism
/ embryology
GABA
androgen receptor
arcuate nucleus
polycystic ovary syndrome
progesterone receptor
Journal
Journal of neuroendocrinology
ISSN: 1365-2826
Titre abrégé: J Neuroendocrinol
Pays: United States
ID NLM: 8913461
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
revised:
14
10
2021
received:
26
02
2021
accepted:
15
10
2021
pubmed:
9
11
2021
medline:
22
3
2022
entrez:
8
11
2021
Statut:
ppublish
Résumé
Prenatal exposure to excess androgens is associated with the development of polycystic ovary syndrome (PCOS). In prenatally androgenised (PNA) mice, a model of PCOS, progesterone receptor (PR) protein expression is reduced in arcuate nucleus (ARC) GABA neurons. This suggests a mechanism for PCOS-related impaired steroid hormone feedback and implicates androgen excess with respect to inducing transcriptional repression of the PR-encoding gene Pgr in the ARC. However, the androgen sensitivity of ARC neurons and the relative gene expression of PRs over development and following prenatal androgen exposure remain unknown. Here, we used a quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR) of microdissected ARC to determine the relative androgen receptor (Ar) and progesterone receptor (Pgr) gene expression in PNA and control mice at five developmental timepoints. In a two-way analysis of variance, none of the genes examined showed expression changes with a statistically significant interaction between treatment and age, although PgrA showed a borderline interaction. For all genes, there was a statistically significant main effect of age on expression levels, reflecting a general increase in expression with increasing age, regardless of treatment. For PgrB and Ar, there was a statistically significant main effect of treatment, indicating a change in expression following PNA (increased for PgrB and decreased for Ar), regardless of age. For PgrA, there was a borderline main effect of treatment, suggesting a possible change in expression following PNA, regardless of age. PgrAB gene expression changes showed no significant main effect of treatment. We additionally examined androgen and progesterone responsiveness specifically in P60 ARC GABA neurons using RNAScope® (Advanced Cell Diagnostics, Inc.) in situ hybridization. This analysis revealed that Pgr and Ar were expressed in the majority of ARC GABA neurons in normal adult females. However, our RNAScope® analysis did not show significant changes in Pgr or Ar expression within ARC GABA neurons following PNA. Lastly, because GABA drive to gonadotropin-releasing hormone neurons is increased in PNA, we hypothesised that PNA mice would show increased expression of glutamic acid decarboxylase (GAD), the rate-limiting enzyme in GABA production. However, the RT-qPCR showed that the expression of GAD encoding genes (Gad1 and Gad2) was unchanged in adult PNA mice compared to controls. Our findings indicate that PNA treatment can impact Pgr and Ar mRNA expression in adulthood. This may reflect altered circulating steroid hormones in PNA mice or PNA-induced epigenetic changes in the regulation of Pgr and Ar gene expression in ARC neurons.
Substances chimiques
RNA, Messenger
0
Receptors, Androgen
0
Receptors, Progesterone
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13058Informations de copyright
© 2021 British Society for Neuroendocrinology.
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