Sequential exposure to estrogen and testosterone (T) and subsequent withdrawal of T increases the level of arginine vasopressin messenger ribonucleic acid in the hypothalamic paraventricular nucleus of the female rat.

The hypothalamic peptides arginine vasopressin (AVP) and oxytocin (OT) have been implicated as mediators of socio-sexual behaviors in addition to their roles in osmolar homeostasis (AVP), milk ejection and uterine contractility (OT). Within 24 h of parturition, OT and AVP messenger ribonucleic acid (mRNA) levels increase in the hypothalamic paraventricular, and to a lesser degree, the supraoptic nucleus (PVN and SON) of the rat. We previously reported that the prepartum increase in OT mRNA is related to the spontaneous decline in progesterone levels prior to parturition. We also reported that increases in PVN and SON OT mRNA can be induced by exposing the ovariectomized rat to a steroid regimen that mimics the steroid milieu of pregnancy, namely sequential estrogen and progesterone and subsequent progesterone withdrawal. Levels of PVN and SON AVP mRNAs were not affected by progesterone withdrawal in late pregnant rats or the steroid regimen that increased OT mRNA in ovariectomized rats. These observations suggest that other factors, perhaps hormonal, may influence AVP mRNA levels. A decline in testosterone coincident with waning progesterone levels also occurs prepartum. Since peak levels of AVP mRNA prepartum coincide with the prepartum decline in testosterone, we questioned whether declining testosterone levels are important for the increase in AVP mRNA levels. To examine a possible role for testosterone in the increased level of AVP mRNA in late pregnancy, we sequentially administered estradiol and testosterone long-term (2 weeks) and removed testosterone 48 h prior to sacrifice. This steroid regimen mimics the estrogen and testosterone pattern of late pregnancy in rats. AVP, but not OT, mRNA levels increased significantly in the PVN of ovariectomized rats receiving this steroid regimen. We also found that implantation of late pregnant rats with testosterone capsules to prevent the spontaneous prepartum decline in testosterone, attenuates the increase in PVN AVP, but not OT, mRNA on day 21 of pregnancy. The data show that sequential estrogen and testosterone and testosterone withdrawal increase the level of PVN AVP mRNA in the female rat.