{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T23:33:28Z","timestamp":1790984008462,"version":"4.1.0"},"reference-count":60,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,11,8]],"date-time":"2021-11-08T00:00:00Z","timestamp":1636329600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001505","name":"Health Research Council of New Zealand","doi-asserted-by":"publisher","award":["18\u2010671"],"award-info":[{"award-number":["18\u2010671"]}],"id":[{"id":"10.13039\/501100001505","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Neuroendocrinology"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    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\u2010related impaired steroid hormone feedback and implicates androgen excess with respect to inducing transcriptional repression of the PR\u2010encoding gene\n                    <jats:italic>Pgr<\/jats:italic>\n                    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\u2010polymerase chain reaction (RT\u2010qPCR) of microdissected ARC to determine the relative androgen receptor (\n                    <jats:italic>Ar<\/jats:italic>\n                    ) and progesterone receptor (\n                    <jats:italic>Pgr<\/jats:italic>\n                    ) gene expression in PNA and control mice at five developmental timepoints. In a two\u2010way analysis of variance, none of the genes examined showed expression changes with a statistically significant interaction between treatment and age, although\n                    <jats:italic>PgrA<\/jats:italic>\n                    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\n                    <jats:italic>PgrB<\/jats:italic>\n                    and\n                    <jats:italic>Ar<\/jats:italic>\n                    , there was a statistically significant main effect of treatment, indicating a change in expression following PNA (increased for\n                    <jats:italic>PgrB<\/jats:italic>\n                    and decreased for\n                    <jats:italic>Ar<\/jats:italic>\n                    ), regardless of age. For\n                    <jats:italic>PgrA<\/jats:italic>\n                    , there was a borderline main effect of treatment, suggesting a possible change in expression following PNA, regardless of age.\n                    <jats:italic>PgrAB<\/jats:italic>\n                    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\u00ae (Advanced Cell Diagnostics, Inc.)\n                    <jats:italic>in situ<\/jats:italic>\n                    hybridization. This analysis revealed that\n                    <jats:italic>Pgr<\/jats:italic>\n                    and\n                    <jats:italic>Ar<\/jats:italic>\n                    were expressed in the majority of ARC GABA neurons in normal adult females. However, our RNAScope\u00ae analysis did not show significant changes in\n                    <jats:italic>Pgr<\/jats:italic>\n                    or\n                    <jats:italic>Ar<\/jats:italic>\n                    expression within ARC GABA neurons following PNA. Lastly, because GABA drive to gonadotropin\u2010releasing hormone neurons is increased in PNA, we hypothesised that PNA mice would show increased expression of glutamic acid decarboxylase (GAD), the rate\u2010limiting enzyme in GABA production. However, the RT\u2010qPCR showed that the expression of GAD encoding genes (\n                    <jats:italic>Gad1<\/jats:italic>\n                    and\n                    <jats:italic>Gad2<\/jats:italic>\n                    ) was unchanged in adult PNA mice compared to controls. Our findings indicate that PNA treatment can impact\n                    <jats:italic>Pgr<\/jats:italic>\n                    and\n                    <jats:italic>Ar<\/jats:italic>\n                    mRNA expression in adulthood. This may reflect altered circulating steroid hormones in PNA mice or PNA\u2010induced epigenetic changes in the regulation of\n                    <jats:italic>Pgr<\/jats:italic>\n                    and\n                    <jats:italic>Ar<\/jats:italic>\n                    gene expression in ARC neurons.\n                  <\/jats:p>","DOI":"10.1111\/jne.13058","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T16:25:12Z","timestamp":1634747112000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Prenatal androgenization causes expression changes of progesterone and androgen receptor mRNAs in the arcuate nucleus of female mice across development"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6920-5360","authenticated-orcid":false,"given":"Yugo","family":"Watanabe","sequence":"first","affiliation":[{"name":"Department of Anatomy Centre 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