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Transcription factor p53 can regulate proliferation, apoptosis and secretory activity of luteinizing porcine ovarian granulosa cell cultured with and without ghrelin and FSH

A Sirotkin, Andrej Beno, Alzbeta Tandlmajerova, Dusan Vaiek, Jan Kotwica, Kristof Darlak and Francisco Valenzuela

A Sirotkin, Department of Genetics and Reproduction, Research Institute of Animal Production, Slovak Centre of Agricultural Studies, Nitra, Slovakia
A Beno, Konstantin the Philosopher University, Nitra, Slovakia
A Tandlmajerova, Konstantin the Philosopher University, Nitra, Slovakia
D Vaiek, Department of Genetics and Reproduction, Research Institute of Animal Production, Slovak Centre of Agricultural Studies, Nitra, Slovakia
J Kotwica, Institute of Animal Reproduction and Food Research, Olsztyn-Kortowo, Poland
K Darlak, Peptides International Inc., Louisville, United States
F Valenzuela, Peptides International Inc., Louisville, United States

Correspondence: A Sirotkin, Email: sirotkin{at}scpv.sk

Abstract

The aim of our in vitro experiments was to examine the role of transcription factor p53 in controlling the basic functions of ovarian cells and their response to hormonal treatments. Transfection with the p53 gene construct promoted accumulation of this transcription factor within cells. It also stimulated the expression of marker of apoptosis (ASK-1). Over-expression of p53 resulted in reduced accumulation of marker of proliferation (cyclin B1), P4 and PGF secretion and increased OT and PGE secretion. Ghrelin, when added alone, did not affect p53 or P4, but reduced ASK-1 and increased PGF and PGE secretion. Over-expression of p53 reversed the effect ghrelin on OT, caused it to be inhibitory to P4 secretion, but did not modify its action on ASK-1, PGF or PGE. FSH promoted the accumulation of p53, ASK-1 and cyclin B1; these effects were unaffected by p53 transfection. These multiple effects of the p53 gene construct on luteinizing granulosa cells, cultured with and without hormones (1) demonstrate the effects of ghrelin and FSH on porcine ovarian cell apoptosis and secretory activity, (2) confirm the involvement of p53 in promoting apoptosis and inhibiting P4 secretion in these cells, (3) provide the first evidence, that p53 suppress proliferation of ovarian cells, (4) provide the first evidence that p53 is involved in the control of ovarian peptide hormone (OT) and prostaglandin (PGF and PGE) secretion, and (5) suggest that p53 can modulate, but probably not mediate the effects of ghrelin and FSH on the ovary.