Neonatal oxytocin alters subsequent estrogen receptor alpha protein expression and estrogen sensitivity in the female rat
Abstract
In most species, the effects of oxytocin (OT) on female reproductive behavior are dependent upon estrogen, which increases both OT and OT receptor expression. It is also becoming apparent that OT neurotransmission can influence estrogen signaling, especially during development, as neonatal OT manipulations in prairie voles alter ERalpha expression and estrogen-dependent behaviors. We tested the hypothesis that OT developmentally programs ERalpha expression and estrogen sensitivity in female Sprague-Dawley rats, a species previously used to establish the estrogen-dependence of OT signaling in adulthood. OT treatment for the first postnatal week significantly increased ERalpha-immunoreactivity in the ventromedial nucleus of the hypothalamus (VMH), but not in the medial preoptic area (MPOA). Conversely, neonatal OT antagonist (OTA) treatment significantly reduced ERalpha-immunoreactivity in the MPOA, but not in the VMH. Both treatments increased OT-immunoreactivity in the paraventricular nucleus of the hypothalamus (PVN) and reduced estrogen sensitivity, indicated by reduced sexual receptivity following chronic estradiol benzoate (EB) administration. Behavioral deficits in OTA-treated females were apparent during both paced and non-paced tests with 0.5 microg EB (but not 5.0 or 10.0 microg EB), whereas deficits in OT-treated females were only observed during the initial paced test with 0.5 and 5.0 microg EB (but not 10.0 microg EB). The current results demonstrate that OT can positively regulate ERalpha expression within the MPOA and VMH during development; however, endogenous OT selectively programs ERalpha expression within the MPOA. Thus, exogenous OT or OTA exposure during development may have long-term consequences on behavior through stable changes in ERalpha and OT expression.
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Rats repeatedly administered oxytocin from postnatal day 0 until postnatal day 7 have increases in estrogen receptor alpha immunoreactivity at postnatal day 75.
“Similar to prairie voles, rats that are repeatedly administered Oxt from PND0 until PND7 have increases in ERα-ir at PND75 (28)”
From Oxytocin during Development: Possible Organizational Effects on Behavior (2015) · cites this paper as [28]
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- Authors
- Perry, A. N., Paramadilok, A., & Cushing, B. S.
- Affiliations
- University of Illinois Chicago (US)
- University of Akron (US)
- Corresponding author
- Cushing, Bruce S.
- ORCID
- Cushing, Bruce S.
- Venue
- Behavioural Brain Research
- Publisher
- Elsevier BV
- Published
- 2009-12
- Volume
- 205
- Issue
- 1
- Pages
- 154-161
- ISSN
- 0166-4328 (ISSN-L)
- OpenAlex
- W1993996960
- Cited by
- 26
- References
- 58
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2019: 1 · 2016: 4 · 2015: 3 · 2014: 4 · 2013: 3
- FWCI
- 2.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Behavioural Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (MH 01992, K01MH001992)
- National Institute on Drug Abuse (F31DA018034)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P01HD038490, HD38490)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- estrogen receptor alpha, estrogen sensitivity, sexual receptivity, ventromedial hypothalamus, medial preoptic area, paraventricular nucleus, oxytocin antagonist, estradiol benzoate, female reproductive behavior, developmental programming, Sprague-Dawley rats
- MeSH terms
- Aging, Animals, Animals, Newborn, Brain, Dose-Response Relationship, Drug, Estradiol, Estrogens, Female, Oxytocin, Paraventricular Hypothalamic Nucleus, Preoptic Area, Random Allocation, Sexual Behavior, Animal, Ventromedial Hypothalamic Nucleus, Rats, Sprague-Dawley, Estrogen Receptor alpha, Rats
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