Discussion In this study, we demonstrated that 1 Akt is constitu tively expressed, but is gradually phosphorylated Erlotinib cancer in cul tured bovine theca cells through exposure to LH. 2 LH stimulated Inhibitors,Modulators,Libraries androstenedione production in theca cells, although addition of the PI3K inhibitors attenuated LH induced androstenedione production. 3 LH increased CYP17A1 mRNA level in theca cells, whereas addition of LY294002 suppressed LH induced CYP17A1 expression in theca cells. 4 although H89 did not affect LH mediated changes in Akt, U0126 inhibited the LH induced Akt phosphorylation, CYP17A1 expression, and androgen production in theca cells. These results suggest that LH stimulates CYP17A1 mRNA expression and androgen production in theca cells via activation of the PI3KAkt pathway, and that the MAPK, not PKA, is involved in LH stimulation of the PI3KAkt cascade in bovine theca cells.

PI3K converts phosphatidylinositol 4,5 biphosphate to phosphatidylinositol 3,4,5 triphosphate, leading to acti vation of downstream kinases including Akt, which in turn phosphorylates Bad, forkhead in rhabdomyosar Inhibitors,Modulators,Libraries coma, Fas associated death domain like IL 1 converting enzyme like inhibitory protein, and X linked inhibitor of apoptosis protein. The body or anti total Akt antibody. Representative images and densitometric data of phos pho Akt contents, expressed as a ratio of phospho Akt to total Akt, are shown. Values show the mean SEM for three experiments. Each experiment was reproduced at least three times. Different letters denote significant differ ences of means.

PI3KAkt activation drives cell through many biological functions, including gene expression, cell cycle, survival, glucidic metabolism, endocytosis and vesicular traffick ing, cell transformation, and oncogenesis. In ovary, FSH and several growth factors are known to activate the PI3KAkt pathway and prevent apoptosis in granulosa cells and cultured Inhibitors,Modulators,Libraries follicles. Although LH has been reported to activate the cAMPPKA pathway and the ERKMAPK pathway in theca cells, whether LH stim ulates the PI3KAkt cascade in theca cells remains unclear. Results of this study show for the first time that 1 LH stimulates Akt phosphorylation in cultured bovine theca cells, and that 2 activation of PI3KAkt is involved in CYP17A1 mRNA expression and androgen production in stimulated Akt phosphorylation in theca cells is responsi ble for these observations reported earlier.

Inhibitors,Modulators,Libraries Both wortmannin and LY294002 are inhibitors of the lipid modifying enzymes known as PI3K, and many researchers perform a parallel study by using both inhibi tors to probe the roles of PI3K in biological processes. However, depending on the concentration examined, Inhibitors,Modulators,Libraries these inhibitors could be non specific and cytotoxic and could complicate the interpretation of their findings. In our from system, the 0.