title: 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.
authors.affiliation: Department of Psychiatry and the Brain Body Center, University of Illinois at Chicago, Chicago, IL 60612, United States.
authors.forename: Adam N
authors.initials: AN
authors.lastname: Perry
authors.forename: Auratip
authors.initials: A
authors.lastname: Paramadilok
authors.forename: Bruce S
authors.initials: BS
authors.lastname: Cushing
mesh_terms: D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D004967:Estrogens / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D010121:Oxytocin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000254:growth & development / Q000502:physiology; D011301:Preoptic Area / Q000187:drug effects / Q000254:growth & development / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012726:Sexual Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D014697:Ventromedial Hypothalamic Nucleus / Q000187:drug effects / Q000254:growth & development / Q000502:physiology
chemical_list: D047628:Estrogen Receptor alpha; D004967:Estrogens; C074283:estradiol 3-benzoate; D004958:Estradiol; D010121:Oxytocin