Molecular aspects of sexual differentiation of the rodent brain
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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Masculinization of the rodent CNS, in contrast to the periphery, is accomplished primarily by the aromatization of testosterone to estrogen.
“Given that the masculinization of the rodent CNS, in contrast to the periphery, is accomplished primarily by the aromatization of testosterone to estrogen (Olsen, 1992, McCarthy, 1994), it is thought that the CNS of the tfm male is largely masculinized and defeminized via this mechanism.”
From Play fighting in androgen-insensitivetfm rats: Evidence that androgen receptors are necessary for the development of adult playful attack and defense (2006) · cites this paper as McCarthy, 1994
The CNS of the tfm male is largely masculinized and defeminized via aromatization of testosterone to estrogen.
“Given that the masculinization of the rodent CNS, in contrast to the periphery, is accomplished primarily by the aromatization of testosterone to estrogen (Olsen, 1992, McCarthy, 1994), it is thought that the CNS of the tfm male is largely masculinized and defeminized via this mechanism.”
From Play fighting in androgen-insensitivetfm rats: Evidence that androgen receptors are necessary for the development of adult playful attack and defense (2006) · cites this paper as McCarthy, 1994
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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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