Session: S72-Novel Signaling in the Ovary
Supported by Found Animals Foundation, Inc.
Room 206 (Moscone Center)
LH triggers the biosynthesis of steroid hormones in the ovary through activation of a cyclic AMP dependent pathway. We have shown that LH activates mammalian target of rapamycin complex 1(mTORC1)signaling network, leading to cell proliferation.We have extended these studies showing that LH-mediated activation of mTORC1 signaling cascade also regulates steroidogenesis in the ovary.Treatment with LH increased the expression of downstream targets of mTORC1,S6 kinase, eIF4E as well as steroidogenic enzymes.Inhibition of mTORC1 blocked these LH-induced responses.Mechanistic studies revealed that inhibition of S6 kinase blocked LH-mediated CREB phosphorylation which, in turn, abrogated LH-induced activation of steroidogenesis. Furthermore, ChiP assays revealed that LH increased the association of CREB with proximal promoter of Cyp 17a1 and this increase was blocked by inhibiting mTROC1. These results show that LH-mediated activation of steroid biosynthesis in the ovary is regulated by mTORC1 signaling pathway.