Signaling and Signal Transduction in Endocrine Tissues
(W747) LH-INDUCED ERK ACTIVATION DIFFERENTLY MODULATES PROGESTERONE AND ANDROSTENEDIONE PRODUCTION IN BOVINE THECA CELLS.
Tajima, Kimihisa1, Yoshii, Kumiko1, Fukuda, Shin1, Orisaka, Makoto1, Miyamoto, Kaoru1, Amsterdam, Abraham2, Kotsuji, Fumikazu1, 1 University of Fukui, Matsuoka-cho, Fukui, Japan2 The Weizmann Institute of Science, Rehovot, Israel
ABSTRACT- It has been reported that gonadotropins promoted phosphorylation of extracellular-signal regulated kinase (ERK) in rat and human granulosa cells. However, little is known about the effects of gonadotropin on ERK activity in theca cells. We explore how LH/forskolin controls ERK phosphorylation in cultured bovine theca cells. Effects of ERK on steroidogenesis were also investigated. Phosphorylation of ERK in bovine theca cells was augmented by LH and forskolin in 5 min; it decreased thereafter below basal levels in 20 min. Nevertheless, phosphorylation of the ERK kinase, MEK, was unaffected. Addition of H89 (a PKA inhibitor) significantly reduced the effect of LH/forskolin on ERK phosphorylation. A potent MEK inhibitor PD98059 eliminated ERK phosphorylation and augmented progesterone production concomitantly with the elevation of intracellular steroidogenic acute regulatory protein (StAR) mRNA in LH/forskolin-stimulated theca cells. In contrast to progesterone production, androgen production was diminished significantly by inhibition of ERK with decreased intracellular P450c17 mRNA levels. Taking these results together, we conclude that LH/cAMP leads to phosphorylation of ERK in a biphasic manner through MEK-independent pathway in bovine theca cells. PKA-induced phosphatase could possibly contribute to the phosphorylation process. Furthermore, modulation of ERK phosphorylation involves control of thecal steroidogenesis via modulation of the expression of StAR and P450c17. Findings of our study provide new evidence that LH-mediated ERK activity plays a pivotal role in the regulation of steroidogenesis in ovarian theca cells.
KEY WORDS: theca, androgen, ovary, ERK