Current data from my laboratory on the activation of steroidogenesis in a clonal strain of cultured Leydig tumor cells (MA-10 cells) show that mouse epidermal growth factor (mEGF) is capable of activating steroid biosynthesis without affecting cAMP levels and that it potentiates the activation of steroidogenesis by hCG and cAMP analogues. These data suggest that steroid biosynthesis can be activated by a """"""""cAMP independent"""""""" pathway(s), and that the activation of this pathway9s) along with the cAMP signalling system leads to the synergistic activation of steroidogenesis. The overall aim of this proposal is to characterize the mechanisms by which LH/CG, mEGF, and other growth factors and hormones activate steroid biosynthesis and modulate the actions of LH/CG in the MA-10 cells.
The specific aims are as follows: (1) Characterize the actions of mEGF, alone and in combination with hCG or cAMP analogues, on the pathway for steroid biosynthesis. (2) Characterize the effects of mEGF on other actions of hCG and cAMP analogues on the MA-10 cells. (3) Characterize the mechanisms by which mEGF modulates the actions of hCG and cAMP analogues. (4) Define the signalling system(s) activated by mEGF in the MA-10 cells and determine if this signalling system(s) is also activated by LH/CG. (5) Determine if the signalling system(s) identified under growth factors and certain hormones (insulin, angiotensin II, and arginine vasopressin) activate steroid biosynthesis and modulate the actions of hCG and cAMP analogues. These studies will allow us a much better understanding of the interaction of different horomones and growth factors in the endocrine, paracrine, and/or autocrine regulation of Leydig cell steroidogenesis. From a more general point of view, these studies will contribute to our understanding of whether a given hormone regulates cellular functions by activating one or more signalling systems, and how different signalling systems lead to the activation of the same cellular function.
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