Transforming growth factor-beta inhibits DNA synthesis in immature rat Leydig cells in vitro.
TGFbeta isoforms and its receptors are present in the testis and regulate in vitro function of various testicular cells. We have investigated the effects of TGFbeta on basal and mitogen stimulated in vitro proliferation of immature rat Leydig cells. Leydig cells were cultured with TGFbeta1, either alone or in combination with hCG, steroidogenesis-inducing protein (SIP), interleukin-1beta (IL-1beta), insulin or TGFalpha, and the incorporation of [3H]thymidine into DNA was determined. TGFbeta1 blocked the stimulatory effects of hCG, SIP, IL-1beta, insulin and TGF-alpha on DNA synthesis. Since G1- to S-phase transition depends upon cyclins and their associated kinases (cdks), we investigated the effects of TGFbeta on cdks. Immunoreactive levels of cdc2 (or cdk1) and cdk2 were significantly decreased in Leydig cells treated with TGFbeta1. We conclude that TGFbeta1 inhibits proliferation of immature rat Leydig cells and this effect may be mediated, at least in part, through down-regulation of cdc2 and cdk2 synthesis.
Khan
S A
SA
Banting and Best Department of Medical Research, University of Toronto, Ontario, Canada. cbbsak@ttuhsc.edu
Mirsafian
M
M
Howdeshell
K
K
Dorrington
J H
JH
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects* / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D016193:G1 Phase; D006360:Heat-Shock Proteins; D007328:Insulin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D007700:Kinetics; D007985:Leydig Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008934:Mitogens / Q000494:pharmacology; D018832:Molecular Chaperones; D011506:Proteins / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016196:S Phase; D013936:Thymidine / Q000378:metabolism; D016211:Transforming Growth Factor alpha / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D000091342:Endoplasmic Reticulum Chaperone BiP
D006063:Chorionic Gonadotropin; D018844:Cyclin-Dependent Kinases; D016213:Cyclins; D004247:DNA; D006360:Heat-Shock Proteins; D007328:Insulin; D007375:Interleukin-1; D008934:Mitogens; D018832:Molecular Chaperones; D011506:Proteins; D013936:Thymidine; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP