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Mechanisms of inhibition of dehydroepiandrosterone upon corticosterone release from rat zona fasciculata‐reticularis cells
Author(s) -
Chang LingLing,
Wun WanSong Alfred,
Wang Paulus S.
Publication year - 2007
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21627
Subject(s) - steroidogenic acute regulatory protein , forskolin , mapk/erk pathway , medicine , endocrinology , cholesterol side chain cleavage enzyme , corticosterone , phosphorylation , dehydroepiandrosterone , protein kinase a , chemistry , steroid 11 beta hydroxylase , biology , microbiology and biotechnology , hormone , gene expression , biochemistry , androgen , steroid , cytochrome p450 , metabolism , gene , stimulation
We have demonstrated that dehydroepiandrosterone (DHEA) acts directly on rat zona fasciculata‐reticularis (ZFR) cells to diminish corticosterone secretion by an inhibition of post‐cAMP pathway, and decreases functions of steroidogenic enzymes after P450 scc as well as steroidogenic acute regulatory (StAR) protein expression. However, the mechanisms by which DHEA engages with environmental messenger signals which translate into interfering StAR protein expression are still unclear. This study explored the effects of DHEA on the phosphorylation/activation of extracellular signal‐regulated kinases (ERKs). ERK activation resulted in enhancing phosphorylation of steroidogenic factor‐1 (SF‐1) and increased StAR protein expression. ZFR cells were incubated in the presence or absence of adrenocorticotropin (ACTH), forskolin (FSK), 25‐OH‐cholesterol, U0126, and H89 at 37°C. The concentration of corticosterone released into the media was measured by radioimmunoassay (RIA). The cells were used to extract protein for Western blot analysis of ERKs or StAR protein expression or immunoprecipitation of SF‐1 analysis. The results suggested that (1) ERK pathway of rat ZFR cells might be PKA dependent, (2) ERK activity was required for SF‐1 phosphorylation to upregulate steroidogenesis in rat ZFR cells, and (3) DHEA did not affect ERK phosphorylation, however, it attenuated forskolin‐stimulated SF‐1 phosphorylation to affect StAR protein expression. J. Cell. Biochem. 104: 359–368, 2008. © 2007 Wiley‐Liss, Inc.