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Abstract

Lactogenic hormone-inducible phosphorylation and gamma-activated binding site binding activities of STAT5b in primary rat Leydig cells and MA-10 mouse Leydig tumor cells 
Kanzaki,Masanori; Morris,Patricia L.
Endocrinology 139(4): 1872-1882
Publication date: 1998


The signal transducer and activator of transcription Stat5bhas been implicated in signal transduction pathways for a numberof cytokines and growth factors, including GH and PRL. Althoughthese lactogenic hormones have the potential to enhance gonadotropin-induced steroidogenesis,the role of GH and PRL in the testis has long been and remainsthe subject of controversy. In this report we provide, to our knowledge,the first evidence of Stat5b protein expression in the testisand characterize the activation of Stat5b by these lactogenic hormonesin primary rat progenitor, immature and adult Leydig cells, andmouse MA-10 Leydig tumor cells. In MA-10 cells, both GH andPRL mediate tyrosine phosphorylation of Janus kinase (JAK) 2and Stat5b and induce DNA-binding activity of Stat5b. GH enhancesboth PIE (PRL-inducible element) and FcRI gamma-activated sites(GAS), but PRL modulates only PIE GAS. In primary Leydig cellsisolated from 18-day-old rats, GH, but not PRL, activates cytoplasmicStat5b and induces the binding of translocated nuclear Stat5bto GAS elements. Although Stat5b protein is expressed in bothPercoll- and elutriator-purified adult rat Leydig cells, neitherGH nor PRL treatment results in Stat5b-DNA binding. Our studiesindicate that the MA-10 cell has the capacity to bind both GHand PRL and provides a useful model system with which to studythe distinct testicular roles of these hormones. Moreover, ourfindings suggest that progenitor and immature Leydig cells arefunctional targets for GH in the immature rat, suggestive ofa role for GH-Stat5b in testicular development. Our data indicatethat lactogenic hormone-inducible transcriptional activationmay target distinct gene expression in a signaling cascade(s)involving Stat5b but also imply coordinate control by multipleLeydig cell factors.