EXPRESSION AND REGION-SPECIFIC REGULATION OF THE OXYTOCIN RECEPTOR GENE IN RAT-BRAIN

The neuropeptide oxytocin (OT) exerts its various neurotransmitter fun ctions via specific OT receptors (OTRs) that have been localized to di stinct brain regions, including the ventromedial hypothalamus, the bed nucleus of stria terminalis, the amygdala, the subiculum, the hippoca mpus, and the olfactory nuclei. In the present study, we have characte rized OTR gene expression by Northern blot and by semiquantitative RT- PCR in these brain regions and studied its regulation in response to e strogen (E-2), progesterone, and the antiestrogen tamoxifen. We find t hat all regions analyzed express two messenger RNA (mRNA) bands (6.7 a nd 4.8 kb) that hybridize to a rat OTR complementary DNA probe and tha t correspond in size to two of the three OTR mRNA bands expressed in r at uterus. Analysis by RT-PCR, with two different primer pairs, did no t reveal any structural differences between the coding regions of uter ine and brain OTR mRNA. E-2 treatment and gestation led to an 8-fold a nd a 6.5-fold increase in OTR mRNA levels, respectively. Progesterone was without effect, if administered alone, and did not influence the E -2-induced rise in OTR mRNA. The E-2 effect was restricted to E-2-sens itive regions, such as the hypothalamus, and was not observed in the s ubiculum or the olfactory nuclei. Tamoxifen had a dual effect: on the one hand, it acted as a partial agonist in raising OTR mRNA levels in the hypothalamus of ovariectomized animals; on the other hand, it supp ressed the E-2-induced OTR mRNA rise in E-2-sensitive brain regions. A lthough the present data do not exclude the possible existence of OTR subtype(s) in brain, they show that the uterine-type OTR gene is expre ssed in all major OTE-containing brain regions. Moreover, they show th at region-specific regulation of OTR gene expression underlies the pre viously observed region-specific steroid regulation of central OT bind ing sites.