STIMULATION OF TESTOSTERONE PRODUCTION BY ATRIAL-NATRIURETIC-PEPTIDE IN ISOLATED MOUSE LEYDIG-CELLS RESULTS FROM A PROMISCUOUS ACTIVATION OF CYCLIC AMP-DEPENDENT PROTEIN-KINASE BY CYCLIC-GMP

被引:32
作者
SCHUMACHER, H
MULLER, D
MUKHOPADHYAY, AK
机构
[1] UNIV HAMBURG,UKE,INST HORMONE & FERTIL RES,GRANDWEG 64,W-2000 HAMBURG 54,GERMANY
[2] UNIV HAMBURG,UKE,INST CELLULAR BIOCHEM & CLIN NEUROBIOL,W-2000 HAMBURG 54,GERMANY
关键词
ATRIAL PEPTIDE HORMONE; LEYDIG CELL; PROTEIN KINASE; CYCLIC NUCLEOTIDE; STEROIDOGENESIS;
D O I
10.1016/0303-7207(92)90100-K
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The aim of this study was to examine the possibility that atrial natriuretic peptide-stimulated testosterone production by mouse Leydig cells results from an activation of cAMP-dependent protein kinase (kinase A) by cGMP. In these cells, both 8Br-cGMP and 8Br-cAMP could stimulate testosterone production, though the latter was approximately 50-fold more potent. Following the stimulation of the cells with the atrial peptide, a dose-related decrease in the cellular protein-bound cAMP accompanied by a concomitant increase in the protein-bound cGMP was observed. The steroidogenesis stimulated by both human chorionic gonadotrophin (hCG) and atrial peptide was inhibited in a dose-dependent manner by a cAMP antagonist, adenosine 3',5'-cyclic monophosphothioate, Rp-isomer (RpcAMPS). In a cell-free [H-3]cAMP binding assay, we have shown that unlabelled cGMP and RpcAMPS could competitively inhibit the [H-3]cAMP binding, confirming that cAMP, RpcAMPS and cGMP could bind to the same binding protein. Finally, in a cell-free kinase A assay system, we have demonstrated that in lysates prepared from either atrial peptide or hCG-stimulated cells, the cellular kinase A was activated to an equal extent. We conclude from the data obtained that cGMP can bind to the cAMP-binding sites of kinase A and thereby brings about a promiscuous activation of this kinase. This appears to be an underlying mechanism by which atrial peptide hormone is able to stimulate the steroidogenesis in mouse Leydig cells.
引用
收藏
页码:47 / 52
页数:6
相关论文
共 18 条
[1]  
BOTELHO LHP, 1988, METHOD ENZYMOL, V159, P159
[2]  
BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
[3]   THE HEART AND THE ATRIAL NATRIURETIC FACTOR [J].
CANTIN, M ;
GENEST, J .
ENDOCRINE REVIEWS, 1985, 6 (02) :107-127
[4]  
COOKE BA, 1983, CURR TOP MEMBR TRANS, V18, P143
[5]  
DARBON JM, 1984, J BIOL CHEM, V259, P4778
[6]  
ERNEUX C, 1985, J CYCLIC NUCL PROT, V10, P463
[7]   INTERACTION BETWEEN CYCLIC-NUCLEOTIDE 2ND MESSENGER SYSTEMS IN MURINE LEYDIG-CELLS [J].
HIPKIN, RW ;
MOGER, WH .
MOLECULAR AND CELLULAR ENDOCRINOLOGY, 1991, 82 (2-3) :251-257
[8]  
JIANG H, 1992, J BIOL CHEM, V267, P1015
[9]   ATRIAL-NATRIURETIC-PEPTIDE IS PHOSPHORYLATED BY INTACT-CELLS THROUGH CAMP-DEPENDENT ECTOPROTEIN KINASE [J].
KUBLER, D ;
REINHARDT, D ;
REED, J ;
PYERIN, W ;
KINZEL, V .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1992, 206 (01) :179-186
[10]   CLEAVAGE OF STRUCTURAL PROTEINS DURING ASSEMBLY OF HEAD OF BACTERIOPHAGE-T4 [J].
LAEMMLI, UK .
NATURE, 1970, 227 (5259) :680-+