Vasopressinergic sexual dimorphism: Sex chromosome complement and organizational hormonal effects

Abstract This study aimed to analyze the role of the sex chromosomes (SCC:XX/XY) and the interaction with organizational hormonal effects on Avp gene expression at the supraoptic (SON) and paraventricular nuclei (PVN) due to water deprivation-osmotic challenge, as well as on the vasopressinergic sexually dimorphic antidiuretic and pressor responses. For this purpose, we used gonadectomized (GDX) transgenic mice of the "four core genotypes" model, in which the effect of gonadal sex and SCC are dissociated. We evaluated a) mRNA Avp gene expression at the SON and PVN at baseline and after 24-hour water deprivation, b) desmopressin antidiuretic response and renal Avpr2 mRNA expression, c) vasopressin-induced bradycardic baroreflex regulation, and d) the pressor and bradycardic responses induced by continuous vasopressin infusion. Our results indicate, in absence of activational hormonal effects, an influence of SCC on basal Avp gene expression at the SON {FSCC (1,6) = 5.44, p<0.05}. Regardless of the organizational hormonal factor, male and female mice with XX-SCC showed a higher basal expression than those with XY-SCC. Furthermore, after 24 h of the osmotic-water deprivation challenge, a significant effect of the interaction between treatment and SCC was observed {F (1,13) = 5.91 p<0.05}. While water deprivation in XY-SCC mice (XY-male-DEP and XY-female-DEP) resulted in an increase in mRNA Avp expression compared to their respective control groups (XY-male-CON and XY-female-CON), SCC-XX mice (XX-Male/GDXDEP and XX-Female/GDX-DEP) showed similar levels of mRNA Avp expression than those reported for their control groups (XX-Male /GDX-CON and XX-Female/GDX--CON). In contrast, a significant interaction of the SCC, organizational hormonal, and treatment factors was observed at the PVN, revealing an increase in the expression of Avp gene expression in the XY-Male/GDX-DEP group. Furthermore, our results demonstrate that, although desmopressin treatment induced the expected antidiuretic effect {F(1,37)=439.63, p≤0,05} in both males and females, no SCC or organizational hormonal effects were observed on the antidiuretic or on renal Avpr2 mRNA expression in absence of activational hormonal influences. Regarding blood pressure regulation, our data also reveal an interplay of organizational hormonal and SCC factors in the homeostatic mechanisms involved in the short {F(5,125)=2.50;p<0.05} and medium-term {F(6,144)=3.891,p<0.005} vasopressin -blood pressure regulation. The analysis of vasopressin-bradycardic baroreflex responses showed a facilitated bradycardic baroreflex response in XX-Females/GDX compared to that reported for the other genotypes (XY-Male /GDX, XX-Male /GDX and XY-Female /GDX). Finally, statistical analysis of the changes in mean arterial pressure due to continuous vasopressin infusion demonstrated that vasopressin infusion resulted in an increase in the percentage change in MAP in all genotypes as expected, but a sustained blood pressure increase was observed in XX-Male/GDX mice compared to XY-male/GDX mice and to female mice (both XX-Female/GDX and XY-Female/GDX). Our data may contribute to understanding the hydromineral and blood pressure regulation of the complex interplay between vasopressin and SCC/organizational hormonal backgrounds.