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

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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.

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Abbreviations

CIS:

cytokine signaling suppressor

FOXO3:

forkhead 3 family transcription factor

GALT:

galactose-1-phosphate uridyltransferase

GAPDH:

glyceraldehyde-3-phos-phate dehydrogenase

HPRT:

hypoxanthine guanine phosphoribosyltransferase

JAK2:

Janus family non-receptor tyrosine kinase 2

PIAS3:

protein inhibitor of activated STAT 3

PrlR:

prolactin receptor

SOCS3:

cytokine signaling suppressor 3

STAT5A:

signal transducer and transcription activator 5A

STAT5B:

signal transducer and transcription activator 5B

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Authors and Affiliations

  1. Lomonosov Moscow State University, Faculty of Biology, 199991, Moscow, Russia

    P. A. Abramicheva, T. A. Balakina, T. A. Schelkunova & O. V. Smirnova

  2. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991, Moscow, Russia

    I. A. Morozov

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  1. P. A. Abramicheva
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  2. T. A. Balakina
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Correspondence to P. A. Abramicheva.

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Compliance with ethical norms. All procedures involving animals were conducted in accordance with the regulations of the Biological Faculty Bioethics Committee, Lomonosov Moscow State University

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Russian Text © The Author(s), 2019, published in Biokhimiya, 2019, Vol. 84, No. 10, pp. 1500–1510.

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Abramicheva, P.A., Balakina, T.A., Morozov, I.A. et al. Prolactin Signaling Pathways Determining Its Direct Effects on Kidneys in the Cholestasis of Pregnancy Model. Biochemistry Moscow 84, 1204–1212 (2019). https://doi.org/10.1134/S0006297919100092

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