Is sex chromosome complement (SCC) responsible for sex differences in kidney V2 receptor (V2R) expression and desmopressin-induced antidiuresis?

GONZALEZ, LIHUE; PORCARI, CINTIA; GODINO, ANDREA; VIVAS, LAURA; CAEIRO, XIMENA

Rosario

Congreso; Sociedad Argentina de Fisiologia. Reunion Anual 2019; 2019

SAFIS

An important number of experimental and clinical studies indicate a clear sexual difference in the antidiuretic response to desmopressin (V2R agonist). Women have a greater sensitivity to desmopressin and are more likely than men to develop hyponatremia in response to similar doses. Furthermore, in intact rats (without neutering) females express higher levels of renal mRNA and proteinV2 receptor (V2R) levels, as well as a major urinary osmolarity response to desmopressin when compared to males. Moreover, in vitro studies have demonstrated that the X-linked V2R gene has high probability of escaping Xinactivation.Our present study aimed to explore the role of the SCC (XX/XY) and/or the organizational hormonal effects of gonadal steroids in the sexually dimorphic response to the antidiuretic desmopressin administration on urinary osmolarity as well as in the relative gene expression of renal V2R. For this purpose, we used male (XX and XY) and female (XX and XY) mice of the ?four core genotype?model, in which the effect of gonadal sex and SCC are dissociated, allowing comparisons of sexually dimorphic traits among XX and XY females, as well as in XX and XY males.Mice aged 60-65 days old, were gonadectomized and forty-two days later were subcutaneously injected with vehicle solution or desmopressin (1 mg/kg). In a different group of animals kidneys were excised for V2R mRNA evaluation by qPCR.As expected desmopressin administration induced a significant effect of treatment {F(1,37)=439,63} however no SCC nor organizational hormonal effects were observed in absence of the activational hormonal effects. In coincidence with this data the analysis of V2R mRNA levels showed no differences between male and female mice as well as among XX and XY mice. All this data in conjunction with previous studies highlights the importance of analyzing in further studies the contribution of the activational hormonal effects as well as the interaction with SCC and organizational hormonal effect in the potential mechanisms involved in sex-specific differences in kidney V2R expression and desmopressin-induced antidiuresis