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Type IV collagen induces down‐regulation of steroidogenic response to gonadotropins in adult rat Leydig cells involving mitogen‐activated protein kinase
Author(s) -
Diaz Emilce S.,
Pellizzari Eliana,
Casanova Marta,
Cigorraga Selva B.,
Denduchis Berta
Publication year - 2005
Publication title -
molecular reproduction and development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 105
eISSN - 1098-2795
pISSN - 1040-452X
DOI - 10.1002/mrd.20259
Subject(s) - biology , medicine , protein kinase a , endocrinology , leydig cell , steroidogenic acute regulatory protein , phosphorylation , receptor , testosterone (patch) , kinase , mitogen activated protein kinase , microbiology and biotechnology , gene expression , biochemistry , hormone , luteinizing hormone , gene
We have previously shown that type IV collagen (α1 (IV) and α2 (IV) collagen chains) (Col‐IV) inhibits testosterone (T) production by Leydig cells (LC). The aim of this study was to analyze mechanism/s by which Col‐IV exerts this effect. No significant differences in the specific binding of hCG to LH/hCG receptors in LC cultured on uncoated or Col‐IV coated plates were observed. An inhibition of cAMP production in hCG‐stimulated LC cultured on Col‐IV was detected. The inhibition exerted by Col‐IV on T production in response to hCG was also observed when cells were stimulated with 8Bromo‐cAMP. In addition, conversion of steroid precursors to T in LC cultured on uncoated and Col‐IV coated plates was similar. On the other hand, we detected an increase of ERK1/2 phosphorylation in hCG‐stimulated LC cultured on Col‐IV. Genistein added to LC cultures reduced the ability of Col‐IV to increase ERK1/2 phosphorylation and reverted the inhibitory effect of Col‐IV on T production. An inhibitor of MEK, PD98059 added to LC cultures also reverted the inhibitory effect of Col‐IV on T production. A decrease of steroidogenic acute regulatory protein (StAR) expression in hCG‐stimulated LC cultured on Col‐IV coated plates that could be reverted by addition of PD98059 to the cultures was also demonstrated. All together these results suggest that Col‐IV inhibits T production in LC by binding to integrins, activating ERK1/2, decreasing cAMP production and decreasing StAR expression. Mol. Reprod. Dev. 72: 208–215, 2005. © 2005 Wiley‐Liss, Inc.