Cited by 94Sexual Differentiation and DisordersEstrogen and related hormone effectsGenetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities

Molecular aspects of sexual differentiation of the rodent brain

McCarthy, Margaret M.·1994·Psychoneuroendocrinology

Abstract

The sexual differentiation of the brain is orchestrated by gonadal steroids during a restricted developmental period and results in permanent changes in the neural substrate including the capacity to support ovulation and expression of sex-specific reproductive behaviors. Sry gene-induced development of testes constitutes a binary switch directing all subsequent differentiation. Androgen produced by the testes of the embryonic male differentiates secondary sex characteristics but also acts in the brain to "masculinize" the neural substrate, many of the latter are the result of aromatization of testosterone to estrogen. Molecular characteristics of aromatase and 5 alpha-reductase enzymes are reviewed. It is assumed that estrogen binds to its receptor which then binds to DNA, inducing transcription of specific genes. Mutations in steroid receptor genes can markedly alter hormone-mediated differentiation. Two questions are addressed: (1), is the assumption correct that estrogen's effects on sexual differentiation are via the classic genomic action of steroids?; and (2) if so, what genes are transcribed as a result of the activated estrogen receptor complex? We have used antisense oligodeoxynucleotides designed to hybridize with and block the translation of mRNA for the estrogen receptor. Administration of antisense into brain of 3-day-old pups had permanent effects on estrogen-induced differentiation as indicated by behavioral and brain morphology differences in adulthood. These…

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Crossref · 10.1016/0306-4530(94)90029-9

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Authors
McCarthy, M. M.
Affiliations
National Institutes of Health (US)
Corresponding author
McCarthy, Margaret M.
Venue
Psychoneuroendocrinology
Publisher
Elsevier BV
Published
1994
Volume
19
Issue
5-7
Pages
415-427
ISSN
0306-4530 (ISSN-L)
OpenAlex
W2060860873
Cited by
94
References
59
Citations by year
2024: 2 · 2022: 2 · 2021: 1 · 2020: 3 · 2018: 2 · 2017: 1 · 2016: 3 · 2015: 3 · 2014: 1 · 2013: 2 · 2012: 1
FWCI
0.27
Type
journal article
Language
en
Open access
closed
Locations
  • Psychoneuroendocrinology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
Keywords
sexual differentiation of the brain, sex steroids, aromatase, 5α-reductase, estrogen receptor, antisense oligodeoxynucleotides, SRY gene, testicular development, androgens
MeSH terms
Animals, Brain, Female, Gene Expression Regulation, Hypothalamus, Male, Receptors, Androgen, Receptors, Estrogen, RNA, Messenger, Sexual Behavior, Animal, Sex Differentiation, Rats

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