Regulation of the Rat Oxytocin Gene by Estradiol

Abstract

Oxytocin (OT) plays a role in reproduction at the level of the pituitary and mammary glands and uterus. This OT is synthesized in the hypothalamo-neurohypophyseal system (HNS). A number of observations have suggested that estrogens regulate the production of OT in the HNS. In this study the effect of 17beta-estradiol on the activity of the OT gene promoter was examined as well as the effect of 17beta-estradiol in vivo on OT messenger ribonucleic acid (mRNA) and peptide revels in the rat HNS. Vasopressin (VP) and its mRNA were also determined in the in vivo studies. The direct transcriptional stimulation of OT gene expression by 17beta-estradiol was studied in two different heterologous expression systems. When a plasmid having nucleotides -363 to +16 of the rat OT gene fused to the firefly luciferase reporter gene was co-transfected with an estrogen receptor expression vector in P19 embryonal carcinoma cells, luciferase activity was stimulated 80-fold by 17beta-estradiol. In estrogen receptor containing MCF-7 cells transfected with a plasmid having nucleotides -188 to +16 of the rat OT gene fused to the chloramphenicol acetyl transferase gene, 17beta-estradiol induced the expression of the chloramphenicol acetyl transferase gene through the cloned promoter element. After in vivo treatment of ovariectomized rats with 17beta-estradiol, levels of OT mRNA and VP mRNA were measured in microdissected supraoptic and paraventricular nuclei as well as VP and OT levels in these nuclei and the pituitary gland. As compared to non-treated ovariectomized rats there was no difference in contents of OT mRNA and VP mRNA in these hypothalamic nuclei and in levels of the peptides in paraventricular nuclei and the pituitary gland. A 30% reduction of the OT content of the supraoptic nuclei only was found, while the VP content did not change. To explain the results immunocytochemical analyses of the hypothalamus were performed, showing that the estrogen receptor was absent in the magnocellular neurons of the supraoptic and paraventricular nuclei. The results demonstrate that the 5'flanking region of the OT gene confers estrogen-sensitivity to transcription of the OT gene. This potential to respond to estrogens is not used in the OT-producing neurons of supraoptic and paraventricular nuclei probably due to the absence of the estrogen receptor.

The effects of long-term estradiol treatment on social behavior and gene expression in adult female rats

“…However, the literature on E 2 regulation of Avp and Oxt in the SON is mixed. Some studies showed that E 2 upregulated (Roy et al, 1999), downregulated (Shughrue et al, 2002; Van Tol et al, 1988), or had no effect on expression (Peter et al, 1990; Rhodes et al, 1981). Our data add to this literature on the SON by showing that long-term E 2 treatment upregulates expression of genes involved in nonapeptide signaling.…”

Chronic exposure to anabolic steroids induces the muscle expression of oxytocin and a more than fiftyfold increase in circulating oxytocin in cattle

“…6. Initially, it was believed that OXT expression was directly regulated by the binding of estrogen to ERE in the promoter region (42,46). However, this mechanism is now in doubt as the ERE in the promoter of OXT is not a good match to the ERE consensus sequence (51,29).…”

Storing maternal memories: Hypothesizing an interaction of experience and estrogen on sensory cortical plasticity to learn infant cues

“…Infusing oxytocin antagonist into the postpartum rat’s NAcc, which is necessary for the consolidation of maternal memory as described in Section 4, impairs the reemergence of maternal behavior when tested 10 days after a 1 hour maternal experience (D’Cunha et al, 2011). While oxytocin expression can also be regulated by estrogen (Richard and Zingg, 1990), this may not occur strongly in the oxytocin-releasing neurons of the rat paraventricular nucleus (Peter et al, 1990; Gimpl and Fahrenholz, 2001), so that a more complete model of maternal sensory memories may require incorporation of distinct roles for both these hormones. Indeed, it should be emphasized that estrogens are only one of the important components of the molecular cascades that regulate maternal memory, but a complete review of all the potential players would be beyond the scope of the current review.…”