Oestrogen and androgen receptor activation contribute to the masculinisation of oxytocin receptors in the bed nucleus of the stria terminalis of rats

Nicholas B. Worley, Kelly M. Dumais, Jingting C. Yuan, Laura E. Newman, Andrea G. Alonso, Tessa C. Gillespie, Nicholas J. Hobbs, S. Marc Breedlove, Cynthia L. Jordan, Remco Bredewold, Alexa H. Veenema

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Oxytocin (OT) often regulates social behaviours in sex-specific ways, and this may be a result of sex differences in the brain OT system. Adult male rats show higher OT receptor (OTR) binding in the posterior bed nucleus of the stria terminalis (pBNST) than adult female rats. In the present study, we investigated the mechanisms that lead to this sex difference. First, we found that male rats have higher OTR mRNA expression in the pBNST than females at postnatal day (P) 35 and P60, which demonstrates the presence of the sex difference in OTR binding density at message level. Second, the sex difference in OTR binding density in the pBNST was absent at P0 and P3, but was present by P5. Third, systemic administration of the oestrogen receptor (ER) antagonist fulvestrant at P0 and P1 dose-dependently reduced OTR binding density in the pBNST of 5-week-old male rats, but did not eliminate the sex difference in OTR binding density. Fourth, pBNST-OTR binding density was lower in androgen receptor (AR) deficient genetic male rats compared to wild-type males, but higher compared to wild-type females. Finally, systemic administration of the histone deacetylase inhibitor valproic acid at P0 and P1 did not alter pBNST-OTR binding density in 5-week-old male and female rats. Interestingly, neonatal ER antagonism, AR deficiency, and neonatal valproic acid treatment each eliminated the sex difference in pBNST size. Overall, we demonstrate a role for neonatal ER and AR activation in setting up the sex difference in OTR binding density in the pBNST, which may underlie sexual differentiation of the pBNST and social behaviour.

Original languageEnglish (US)
Article numbere12760
JournalJournal of Neuroendocrinology
Volume31
Issue number8
DOIs
StatePublished - Jan 1 2019

Fingerprint

Oxytocin Receptors
Septal Nuclei
Androgen Receptors
Estrogen Receptors
Sex Characteristics
Social Behavior
Valproic Acid
Oxytocin
Androgen-Insensitivity Syndrome
Sex Differentiation
Histone Deacetylase Inhibitors
Messenger RNA

Keywords

  • androgen receptor
  • bed nucleus of the stria terminalis
  • masculinisation
  • oestrogen receptor
  • oxytocin receptor
  • sex difference

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

Cite this

Oestrogen and androgen receptor activation contribute to the masculinisation of oxytocin receptors in the bed nucleus of the stria terminalis of rats. / Worley, Nicholas B.; Dumais, Kelly M.; Yuan, Jingting C.; Newman, Laura E.; Alonso, Andrea G.; Gillespie, Tessa C.; Hobbs, Nicholas J.; Breedlove, S. Marc; Jordan, Cynthia L.; Bredewold, Remco; Veenema, Alexa H.

In: Journal of Neuroendocrinology, Vol. 31, No. 8, e12760, 01.01.2019.

Research output: Contribution to journalArticle

Worley, NB, Dumais, KM, Yuan, JC, Newman, LE, Alonso, AG, Gillespie, TC, Hobbs, NJ, Breedlove, SM, Jordan, CL, Bredewold, R & Veenema, AH 2019, 'Oestrogen and androgen receptor activation contribute to the masculinisation of oxytocin receptors in the bed nucleus of the stria terminalis of rats', Journal of Neuroendocrinology, vol. 31, no. 8, e12760. https://doi.org/10.1111/jne.12760
Worley, Nicholas B. ; Dumais, Kelly M. ; Yuan, Jingting C. ; Newman, Laura E. ; Alonso, Andrea G. ; Gillespie, Tessa C. ; Hobbs, Nicholas J. ; Breedlove, S. Marc ; Jordan, Cynthia L. ; Bredewold, Remco ; Veenema, Alexa H. / Oestrogen and androgen receptor activation contribute to the masculinisation of oxytocin receptors in the bed nucleus of the stria terminalis of rats. In: Journal of Neuroendocrinology. 2019 ; Vol. 31, No. 8.
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AU - Newman, Laura E.

AU - Alonso, Andrea G.

AU - Gillespie, Tessa C.

AU - Hobbs, Nicholas J.

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AB - Oxytocin (OT) often regulates social behaviours in sex-specific ways, and this may be a result of sex differences in the brain OT system. Adult male rats show higher OT receptor (OTR) binding in the posterior bed nucleus of the stria terminalis (pBNST) than adult female rats. In the present study, we investigated the mechanisms that lead to this sex difference. First, we found that male rats have higher OTR mRNA expression in the pBNST than females at postnatal day (P) 35 and P60, which demonstrates the presence of the sex difference in OTR binding density at message level. Second, the sex difference in OTR binding density in the pBNST was absent at P0 and P3, but was present by P5. Third, systemic administration of the oestrogen receptor (ER) antagonist fulvestrant at P0 and P1 dose-dependently reduced OTR binding density in the pBNST of 5-week-old male rats, but did not eliminate the sex difference in OTR binding density. Fourth, pBNST-OTR binding density was lower in androgen receptor (AR) deficient genetic male rats compared to wild-type males, but higher compared to wild-type females. Finally, systemic administration of the histone deacetylase inhibitor valproic acid at P0 and P1 did not alter pBNST-OTR binding density in 5-week-old male and female rats. Interestingly, neonatal ER antagonism, AR deficiency, and neonatal valproic acid treatment each eliminated the sex difference in pBNST size. Overall, we demonstrate a role for neonatal ER and AR activation in setting up the sex difference in OTR binding density in the pBNST, which may underlie sexual differentiation of the pBNST and social behaviour.

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