title: Effects of retinoic acid and estrogens on oxytocin gene expression in the rat uterus: in vitro and in vivo studies.
abstract: We and others have previously identified functional estrogen (E) and retinoic acid (RA) response elements in the human and rat oxytocin (OT) gene promoters. Whereas there is no direct evidence for a significant role of E or RA in the regulation of rat hypothalamic OT gene expression, we have recently demonstrated that in vivo administration of E strongly stimulates uterine OT gene expression. Here, we show that in vivo administration of RA similarly induces a significant increase in uterine OT gene expression. Moreover, we report that the E and RA effects are reproducible in vitro. Using short-term uterine organ explant cultures derived from 18-day pregnant rats, we found that E (50 nM) and RA (0.4 nM) increased OT mRNA levels 5.2- and 3-fold, respectively, suggesting a direct action of these agents on uterine OT gene expression. Finally, we analyzed uterine E and RA receptor gene expression during pregnancy. Using semi-quantitative Northern blot analysis, we found that mRNAs encoding the E receptor, the RA receptor alpha and RA receptor beta are present in rat uterus and that their levels rise by 3.7-, 3.6- and 5.8-fold, respectively, between day 14 of gestation and term. Taken together, the data suggest that, at term, the rat uterus has an increased capacity to respond to E and RA, and that both agents may be involved in mediating the dramatic increase of OT mRNA accumulation observed in the uterus at term.
authors.affiliation: Laboratory of Molecular Endocrinology, Royal Victoria Hospital, McGill University, Montreal, Que., Canada.
authors.forename: A
authors.initials: A
authors.lastname: Larcher
authors.forename: J
authors.initials: J
authors.lastname: Neculcea
authors.forename: K
authors.initials: K
authors.lastname: Chu
authors.forename: H H
authors.initials: HH
authors.lastname: Zingg
mesh_terms: D000818:Animals; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007774:Lactation; D010121:Oxytocin / Q000235:genetics*; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000235:genetics; D014212:Tretinoin / Q000494:pharmacology*; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D011960:Receptors, Estrogen; D018168:Receptors, Retinoic Acid; D004958:Estradiol; D010121:Oxytocin; D014212:Tretinoin