Activation of multiple signal transduction pathways by glucocorticoids: protection of ovarian follicular cells against apoptosis.
We have recently demonstrated that glucocorticoids protect against serum-deprivation, cAMP-, TNFalpha-, and p53-induced apoptosis in ovarian follicular cells involved in up-regulation of Bcl-2. We demonstrated that dexamethasone, which enhances steroidogenesis by up-regulation of the p450scc enzyme system, stimulates the MAPK cascade by phosphorylation of ERK1, ERK2 as well as by Akt phosphorylation within 1-5min with no effect on p38 MAPK phosphorylation. Moreover, glucocorticoids enhance expression of connexin 43, formation of gap junctions, expression of cadherins, and formation of adherence junctions within 24h of hormone stimulation of ovarian granulosa cells. It is suggested that the protective effects of glucocorticoids against apoptosis are mediated by both genomic and non-genomic mechanisms. Moreover, for the first time we show that protein phosphorylation, cell-cell contact, and intracellular communication are important mediators in glucocorticoid protection against apoptosis in ovarian follicular cells.
Sasson
R
R
Department of Molecular Cell Biology, The Weizmann Institute of Science, 76100, Rehovot, Israel.
Shinder
V
V
Dantes
A
A
Land
A
A
Amsterdam
A
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D006107:Granulosa Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D006080:Ovarian Follicle / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D011374:Progesterone / Q000096:biosynthesis; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology*; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology
D005938:Glucocorticoids; D005576:Colforsin; D011374:Progesterone; D003907:Dexamethasone