Sex differences in and effects of estrogen on oxytocin receptor messenger ribonucleic acid expression in the ventromedial hypothalamus
Abstract
In situ hybridization techniques were used in the present study to detect hypothalamic expression of the oxytocin receptor (OR) gene. Binding studies have localized OR to various brain regions and have detected a high density of receptors in the ventromedial hypothalamus (VMH), a documented target of estrogen action. This study was designed to compare levels of OR messenger RNA (mRNA) in the VMH of male and female rats and to study the effects of estrogen treatment on mRNA levels in the VMH of female rats. After cloning a rat OR gene from a genomic testes library, a probe was generated for use in in situ hybridization assays to evaluate sex differences in OR mRNA expression in the VMH. In addition, ovariectomized females were treated with estrogen, and VMH OR mRNA expression was compared with that in ovariectomized or intact females. The results of these studies showed that male rats expressed higher levels of OR mRNA in the VMH than females. Estrogen-treated ovariectomized females exhibited significantly greater expression in the VMH than either oil-treated or intact females. These results support binding studies that have shown oxytocin binding in the VMH to be regulated by gonadal steroids and suggest that estrogen may either directly or indirectly regulate transcription of the OR gene.
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Androgens and progesterone modulate oxytocin and oxytocin receptor expression, while estrogens seem to have the greatest impact on the oxytocin system.
“While androgens and progesterone modulate Oxt and Oxtr expression (72–75), it is the estrogens that seem to have the greatest impact on the Oxt system (68, 70, 74, 76–78).”
From Oxytocin during Development: Possible Organizational Effects on Behavior (2015) · cites this paper as [73]
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“Indeed, later studies consistently found higher OTR mRNA expression (Bale and Dorsa, 1995) and higher OTR binding density ([using the specific OTR antagonist d(CH2)5[Tyr(Me)2,Thr4,Orn8,[125I]Tyr9-NH2]-OVTA; Uhl-Bronner et al., 2005) in males compared to females in the VMH of Long-Evans and…”
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- Authors
- Bale, T. L.
- Affiliations
- University of Washington (US)
- ORCID
- Bale, T. L.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 1995-01-01
- Volume
- 136
- Issue
- 1
- Pages
- 27-32
- ISSN
- 0013-7227 (ISSN-L)
- OpenAlex
- W2086931455
- Cited by
- 102
- References
- 0
- Citations by year
- 2026: 5 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 3 · 2021: 1 · 2019: 2 · 2018: 3 · 2017: 2 · 2016: 5 · 2015: 4 · 2014: 3 · 2013: 6 · 2012: 1
- FWCI
- 12.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS-07332, NS-20311, R01NS020311)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- oxytocin receptor, ventromedial hypothalamus, sex differences, estrogen, mRNA expression, ovariectomy, sex steroids, transcriptional regulation, rat brain
- MeSH terms
- Animals, Autoradiography, Base Sequence, Estradiol, Female, Humans, Male, Molecular Sequence Data, Ovariectomy, Rats, Inbred Strains, RNA, Messenger, Sex Characteristics, Ventromedial Hypothalamic Nucleus, Rats, Wistar, In Situ Hybridization, Receptors, Oxytocin, Rats
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