Neonatal manipulation of oxytocin affects expression of estrogen receptor alpha
Abstract
In adult females many of the effects of the neuropeptide oxytocin are steroid, and especially estrogen dependent. Here we demonstrate for the first time that neonatal manipulation of oxytocin can affect the expression of estrogen receptor alpha. On the first day of postnatal life male and female prairie voles (Microtus ochrogaster) were randomly assigned to receive one of four treatments; (a) 50 microl i.p. injection of 3 microg oxytocin (approximately 1 microg/g), (b) 0.3 microg of an oxytocin antagonist (approximately 0.1 microg/g), or (c) isotonic saline. A fourth group was handled, but not injected. On postnatal day 8 or 21, brain tissue was collected, fixed and sectioned. Free-floating sections were stained for estrogen receptor alpha using immunocytochemistry, and estrogen receptor alpha immunoreactive neurons were compared by age, treatment, and sex. To compare the temporal expression of estrogen receptor alpha an additional set of brains was collected from untreated males and females on the day of birth. The effects of oxytocin manipulations were age dependent, sexually dimorphic, and site-specific. While there were no significant treatment effects on postnatal day 8, by postnatal day 21 females that received oxytocin showed a significant increase in the number of cells expressing estrogen receptor alpha-immunoreactivity in the ventromedial nucleus of the hypothalamus. Treatment with oxytocin antagonist resulted in a significant decrease in estrogen receptor alpha-immunoreactivity in the medial preoptic area in postnatal day 21 females. While there were no significant effects in males, males treated with oxytocin antagonist trended toward a reduction in estrogen receptor alpha-immunoreactivity in the medial amygdala. The results indicate that oxytocin can have organizational effects on the expression of estrogen receptor alpha, that these effects are sexually dimorphic, and finally that during the preweaning period the development of estrogen receptor alpha is sexually dimorphic.
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In female, but not male, prairie voles, neonatal OTR antagonist decreased ERα-immunoreactivity in the MPOA.
“neonatal OT increased ERα-immunoreactivity in the VMH while OTR antagonist decreased ERα-immunoreactivity in the MPOA in females, but not males”
From Vasopressin and oxytocin receptor systems in the brain: Sex differences and sex-specific regulation of social behavior (2016) · cites this paper as Yamamoto et al., 2006
In female, but not male, prairie voles, neonatal OT increased ERα-immunoreactivity in the VMH.
“neonatal OT increased ERα-immunoreactivity in the VMH while OTR antagonist decreased ERα-immunoreactivity in the MPOA in females, but not males”
From Vasopressin and oxytocin receptor systems in the brain: Sex differences and sex-specific regulation of social behavior (2016) · cites this paper as Yamamoto et al., 2006
i.p. injections of either OT or OTR antagonist on postnatal day 1 induced sex-specific changes in OT, ERα, and V1aR in adult prairie voles.
“i.p. injections of either OT or OTR antagonist on postnatal day 1 induced sex-specific changes in OT, estrogen receptor alpha (ERα), and V1aR in adult prairie voles.”
From Vasopressin and oxytocin receptor systems in the brain: Sex differences and sex-specific regulation of social behavior (2016) · cites this paper as Yamamoto et al., 2006
Neonatal injections of oxytocin increase estrogen receptor alpha expression in the ventromedial hypothalamus of adult females, and oxytocin treatment on postnatal day 0 increases the number of estrogen receptor alpha-immunoreactive cells in the ventromedial hypothalamus of 3-week-old prairie voles.
“Neonatal injections of Oxt increase ERα expression in the ventromedial hypothalamus (VMH) of adult females and Oxt treatment on PND0 increases the number of ERα-immunoreactive (ERα-ir) cells in the VMH of 3-week-old prairie voles (26).”
From Oxytocin during Development: Possible Organizational Effects on Behavior (2015) · cites this paper as [26]
In females, a single injection of an oxytocin receptor antagonist on postnatal day 1 decreases expression of estrogen receptor alpha in the medial preoptic area of adult female prairie voles, increases estrogen receptor alpha expression in the BNST, and possibly decreases expression in the medial amygdala.
“These results differ from reports in females where a single injection of an OTA on PND1 decreases expression of ERα in the medial preoptic area (MPOA) of adult female prairie voles, as well as increases ERα expression in the BNST, and possibly decreases expression in the medial amygdala (MeA) (26)”
From Oxytocin during Development: Possible Organizational Effects on Behavior (2015) · cites this paper as [26]
Work from Bruce Cushing's laboratory suggests that the BNST and medial amygdala are particularly important for the developmental effects of oxytocin and estrogen receptor alpha on social behavior.
“Work from Bruce Cushing’s laboratory suggests that the BNST and MeA are particularly important for the developmental effects of Oxt and ERα on social behavior (24, 26, 94)”
From Oxytocin during Development: Possible Organizational Effects on Behavior (2015) · cites this paper as [26]
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Self-citation
- Authors
- Yamamoto, Y., Carter, C. S., & Cushing, B. S.
- Affiliations
- University of Illinois Chicago (US)
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2006
- Volume
- 137
- Issue
- 1
- Pages
- 157-164
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W2071876581
- Cited by
- 70
- References
- 36
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 3 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 5 · 2016: 8 · 2015: 6 · 2014: 1 · 2013: 6 · 2012: 1
- FWCI
- 5.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (MH 01992, K01MH001992)
- 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
- oxytocin, estrogen receptor alpha, neonatal manipulation, Microtus ochrogaster, sexual differentiation, organizational effects, ventromedial hypothalamus, medial preoptic area, medial amygdala, oxytocin antagonist, postnatal development, sex differences
- MeSH terms
- Animals, Animals, Newborn, Brain, Arvicolinae, Female, Immunohistochemistry, Male, Oxytocin, Sex Characteristics, Estrogen Receptor alpha
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