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Abstract

Gonadotropins, via cAMP, negatively regulate GATA-1 gene expression in testicular cells 
Zhang,Zhifang; Wu,Ai Zhen; Feng,Zong-Ming; Mruk,Dolores D.; Cheng,Chuen-yan; Chen,Ching-Ling C.
Endocrinology 143(3): 829-836
Publication date: 2002


We and others demonstrated that the mRNAs encoding GATA-bindingproteins, GATA-1 and GATA-4, were detected in mouse and rattestis, and in isolated rat Sertoli cells and testicular tumorcell lines derived from Leydig and Sertoli cells. In this study,we investigated the possible effects of gonadotropins and cAMPon the expression of GATA-binding protein genes in testicularcells. Unexpectedly, FSH negatively regulated GATA-1 (but notGATA-4) mRNA in a dose-dependent manner in primary culturesof rat Sertoli cells isolated from 21-d-old animals. GATA-1mRNA was also negatively regulated by cAMP in a dose- and time-dependentmanner in MA-10, a mouse Leydig tumor cell line. When 0.3 mMcAMP was administered to MA-10 cell cultures for 4 h, more than95% of the GATA-1 mRNA and protein was abolished. The reductionof GATA-1 mRNA by cAMP can be mimicked by treatment with forskolin,which elevates intracellular cAMP levels. The inhibitory effectof cAMP was specific to the GATA-1 gene, given that GATA-4 and-tubulin mRNA levels were not changed by any of the cAMP treatments.Inhibin -subunit mRNA, on the other hand, was evidently increasedby cAMP treatment in both MA-10 and Sertoli cells. However,inhibin -subunit mRNA levels were elevated at 60-90 minbefore the suppression of GATA-1 mRNA detected. The inhibitoryeffect of cAMP on GATA-1 mRNA and protein was shown to be specificto testicular cells. The GATA-1 mRNA expressed in MEL, a mouseerythroid leukemia cell line, was not affected by cAMP. Thereduction of GATA-1 mRNA by cAMP can be prevented when a translationalinhibitor, cycloheximide, is added. In summary, we demonstratedthat gonadotropins via cAMP negatively regulate the mRNA andprotein levels of GATA-1, but not GATA-4, in testicular cells.The inhibitory effect on GATA-1 gene expression was specificto testicular cells and was not observed in erythroid cells.