Gonadal steroid regulation of oxytocin and oxytocin receptor gene expression.
By Northern blot analysis and in situ hybridization, we have determined that, at term, the rat uterine epithelium represents a major site of oxytocin (OT) gene expression. OT mRNA levels increase > 150-fold during pregnancy and, at term, exceed hypothalamic OT mRNA by a factor of 70. By cryoultramicroscopy, OT immunoreactivity was localized to transport vesicles in the apical compartment of uterine epithelial cells. Estrogens (E) act as a strong inducer of uterine OT gene expression in vivo, and this effect is potentiated 7-fold by concomitant progesterone (P) administration. We have also cloned the rat OT receptor (OTR) gene and developed a polymerase chain reaction (PCR)-based assay to measure OTR mRNA. Whereas OTR mRNA is strongly induced by E, P does not potentiate but slightly attenuates the E-induced rise. However, E-induced OT binding is completely reversed by concomitant P administration, suggesting an additional post-transcriptional effect of P. The mechanisms of E-induction of the uterine OT gene remain unclear, inasmuch as the OTR gene promoter does not contain a classical estrogen response element (ERE). Moreover, transfection analysis of a 3.1 kb OTR gene promoter fragment linked to a luciferase reporter gene indicates that promoter activity is induced 5-fold by calcium ionophore A23187 but not by E.
Zingg
H H
HH
Laboratory of Molecular Endocrinology, Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada.
Rozen
F
F
Breton
C
C
Larcher
A
A
Neculcea
J
J
Chu
K
K
Russo
C
C
Arslan
A
A
D000818:Animals; D001483:Base Sequence; D018076:DNA, Complementary / Q000235:genetics; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008969:Molecular Sequence Data; D010121:Oxytocin / Q000235:genetics*; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D018045:Receptors, Oxytocin / Q000235:genetics*; D013256:Steroids / Q000378:metabolism*; D014599:Uterus / Q000378:metabolism
D018076:DNA, Complementary; D004967:Estrogens; D012333:RNA, Messenger; D018045:Receptors, Oxytocin; D013256:Steroids; D011374:Progesterone; D010121:Oxytocin