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

Abstract

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.

Hypothalamic Vasopressin Gene Expression Increases in Both Males and Females Postpartum in a Biparental Rodent

“…A significant increase in vasopressin mRNA in the paraventricular nucleus and supraoptic nucleus following parturition and during lactation was found in both male and female prairie voles but not montane voles. Several studies have examined the postpartum increase in hypothalamic vasopressin (12, 13, 34) and its hormonal regulation in female rats (35). Increased hypothalamic vasopressin postpartum was not the result of suckling (36).…”

Neuroendocrine underpinning of social recognition in males and females

“…Both AR and ER mechanisms may be at play, as supported by the fact that AVP gene expression in the PVN increases after treatment with 17βestradiol and testosterone in ovariectomized rats. 131 The effects of estradiol on the AVP system are further supported by the decreased immunoreactivity levels in the LS, MeA and BNST in male ArKO mice, lacking the aromatase enzyme. 132 Several studies with ArKO mice demonstrated that estradiol has strong organizational and activational effects on socio-sexual recognition in male mice.…”

“…Testosterone's effects on the AVP and OT systems may be mediated directly via its biding at the AR or by ERs after its conversion into 17β‐estradiol by the enzyme aromatase (Figure 3). Both AR and ER mechanisms may be at play, as supported by the fact that AVP gene expression in the PVN increases after treatment with 17β‐estradiol and testosterone in ovariectomized rats 131 . The effects of estradiol on the AVP system are further supported by the decreased AVP immunoreactivity levels in the LS, MeA and BNST in male ArKO mice, lacking the aromatase enzyme 132 .…”

Vasopressin and alcohol: a multifaceted relationship

“…There are sex differences in the VP system, which are partly thought to stem from the fact that many VP neurons also contain gonadal steroid hormone receptors and gonadal steroid hormones have been shown to control the synthesis of VP (Carter 2007; Pak et al 2009; Thomas et al 1996; van Leeuwen et al 1985; Zhou et al 1994). In many species, including humans, males have more VP immunoreactive fibers, more VP immunoreactive neurons, VP neurons of larger size, and altered V1a receptor binding densities (De Vries and Panzica 2006; DiBenedictis et al 2017; Dumais and Veenema 2016; Ishunina and Swaab 1999; Rood et al 2013; Smith et al 2017; Winslow et al 1993).…”