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Cited by 89Sexual Differentiation and DisordersHypothalamic control of reproductive hormonesGenetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities

Expression of the nuclear receptor coactivator, cAMP response element-binding protein, is sexually dimorphic and modulates sexual differentiation of neonatal rat brain

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Auger, A. P., Perrot-Sinal, T. S., Auger, C. J., Ekas, L. A., Tetel, M. J., McCarthy, M. M.·2002·Endocrinology
DOI 10.1210/en.143.8.3009PMC PMC2683357
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Abstract

Recent studies indicate that the transcriptional activity of steroid receptors is governed by proteins called nuclear receptor coactivators. Using immunocytochemistry, we found that on the day of birth (postnatal d 0) males express higher levels of the nuclear receptor coactivator, cAMP response element binding protein-binding protein (CBP), within the ventromedial hypothalamus, medial preoptic area, and arcuate nucleus. Using Western immunoblots, we confirmed that males have higher levels of CBP on postnatal d 0, 1, and 5; however, there was no sex difference on postnatal d 11. To examine the functional role of CBP, we infused oligodeoxynucleotides that were antisense to CBP mRNA or a scrambled sequence as a control into the hypothalamus of female rats on postnatal d 0, 1, and 2. On postnatal d 1, all rats were injected with 100 microg testosterone propionate to both masculinize (increase male) and defeminize (decrease female) sexual behavior. Rats were ovariectomized in adulthood and tested for adult sexual behavior. Neonatal CBP antisense oligodeoxynucleotides treatment interfered with the defeminizing, but not the masculinizing, actions of testosterone. These results indicate that CBP expression in developing rat brain is sexually dimorphic and an important modulator for steroid hormone action.

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Cited by

Sorted by citations

Authors
Auger, A. P., Perrot-Sinal, T. S., Auger, C. J., Ekas, L. A., Tetel, M. J., & McCarthy, M. M.
Affiliations
  • University of Maryland, Baltimore (US)
  • Johns Hopkins University (US)
  • Skidmore College (US)
ORCID
Venue
Endocrinology
Publisher
The Endocrine Society
Published
2002-08-01
Volume
143
Issue
8
Pages
3009-3016
ISSN
  • 0013-7227 (ISSN-L)
  • 1945-7170
DOI
10.1210/en.143.8.3009
PMC
PMC2683357
OpenAlex
W2161218552
Cited by
89
References
5
Citations by year
2023: 1 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 3 · 2017: 1 · 2016: 6 · 2015: 6 · 2014: 1 · 2013: 9 · 2012: 7
FWCI
2.20
Type
journal article
Language
en
Open access
Locations
  • Endocrinology (publishedVersion, public-domain)
  • Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Wellesley College Digital RepositoryWellesley (Wellesley College) (submittedVersion)
Funders
  • National Institutes of Health
  • National Institute of Mental Health (K01MH002035, R29MH052716, MH 02035, MH 52716, Z01MH002035, R01MH052716)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK61935, R55DK061935, R01DK061935)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
Keywords
CREB, CBP, nuclear receptor coactivators, sexual differentiation of the brain, sexually dimorphic gene expression, neonatal brain development, hypothalamus, medial preoptic area, arcuate nucleus, testosterone, masculinization, defeminization, antisense oligodeoxynucleotides, steroid hormone action, sex differences
MeSH terms
Animals, Animals, Newborn, Brain, DNA-Binding Proteins, Female, Immunohistochemistry, Nuclear Proteins, Phosphorylation, Sex Characteristics, Sex Differentiation, Testosterone, Transcription Factors, Blotting, Western, Trans-Activators, Oligonucleotides, Antisense, Rats, Sprague-Dawley, Cyclic AMP Response Element-Binding Protein, CREB-Binding Protein, Rats, Activating Transcription Factor 1

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