Renal oxytocin receptor messenger ribonucleic acid: characterization and regulation during pregnancy and in response to ovarian steroid treatment.
Although the neurohypophyseal hormone oxytocin (OT) is best know for its role in reproduction, OT also stimulates natriuresis at physiological plasma levels. This effect is mediated via specific renal OT receptors (OTRs). In the present study, we have characterized rat renal OTR gene transcripts and assessed their regulation during gestation and in response to gonadal steroid treatment. Using a specific rat OTR probe, two major OTR messenger RNA (mRNA) bands [6.7 and 4.8 kilobases (kb)] were detected in renal extracts, corresponding to two of the three bands present in rat uterus. In contrast to the dramatic rise of OTR mRNA levels at term in the uterus and pituitary, renal OTR mRNA levels underwent a strong more than 3-fold decrease at term. Binding studies using a iodinated specific OT antagonist revealed a concomitant decrease in renal OT-binding sites. On the other hand, estrogen (E2) treatment led to an increase in renal OTR mRNA levels, as is also the case in the uterus and pituitary. However, the predominant E2-induced mRNA species were shorter (3.6 and 3.2 kb) than those present in control rat kidneys (6.7 and 4.8 kb). Analysis by reverse transcriptase-PCR and 5'- and 3'-directed complementary DNA probes indicated that the E2-induced OTR mRNA transcripts possessed the same coding region, but contained a shortened 3'-untranslated region. Binding studies showed that E2 treatment also led to an increase in renal OT-binding sites, suggesting that the shortened OTR transcripts encoded a functional receptor. The present study indicates that the uterine-type OTR gene is expressed in rat kidneys, but that the mechanisms controlling the expression of this gene in the two tissues are markedly different. The differential tissue-specific regulation of OTR gene expression may represent a mechanism by which circulating OT can assume a multifunctional role in both reproduction and sodium homeostasis.
Breton
C
C
Laboratory of Molecular Endocrinolog, Royal Victoria Hospital, Montreal, Québec, Canada.
Neculcea
J
J
Zingg
H H
HH
D000818:Animals; D018076:DNA, Complementary; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007438:Introns; D007668:Kidney / Q000378:metabolism*; D007743:Labor, Obstetric; D007774:Lactation / Q000502:physiology; D015345:Oligonucleotide Probes; D010052:Ovariectomy; D010902:Pituitary Gland / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018045:Receptors, Oxytocin / Q000096:biosynthesis*; D014158:Transcription, Genetic / Q000187:drug effects; D014599:Uterus / Q000378:metabolism
D018076:DNA, Complementary; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D018045:Receptors, Oxytocin; D004958:Estradiol