Prolactin Signaling Pathways Determining Its Direct Effects on Kidneys in the Cholestasis of Pregnancy Model.

Abstract

Cholestasis of pregnancy is a pathology associated with disruptions in the bile flow and dysregulation of salt and water homeostasis. Prolactin is one of the most important regulators of salt and water balance. Changes in the expression of long and short isoforms of the prolactin receptor (PrlR) and mediators of prolactin signaling were studied by immunoblotting and RT-qPCR in the rat kidney cortex and outer medulla in the model of cholestasis of pregnancy. Both PrlR isoforms were shown to participate in the effects of prolactin in cholestasis of pregnancy. Direct impact of prolactin on the kidney has been demonstrated: (i) mRNA expression of both PrlR isoforms in the kidney depended on the physiological conditions and prolactin levels; (ii) expression of pSTAT5, a key mediator of the long PrlR isoform signaling, was increased in animals with cholestasis of pregnancy; (iii) in the case of long PrlR isoform predomination, expression of mRNAs for the prolactin signaling inhibitors SOCS3 and PIAS3 was upregulated (the genes of these regulators contain STAT-responsive elements in their promoters); (iv) expression of the mRNA for galactose-1-phosphate uridyltransferase (GALT), a molecular target of the PrlR short isoform, was decreased in the kidney outer medulla.