Growth factor modulation of steroidogenic acute regulatory protein and luteinization in the pig ovary

In vivo and in vitro luteinization were investigated in the porcine ovary, with emphasis on expression of steroidogenic acute regulatory protein (StAR). SMR mRNA and protein as well as cytochrome P450 side-chain cleavage mRNA (P450(arom)) increased during the luteal phase in the corpus luteum (CL) and were absent in regressed CL. Cytochrome P450 aromatase mRNA (P450(arom)) was not detectable at any time in CL. In vitro luteinization of granulosa cells occurred over 96 h in culture, during which P450(arom) mRNA was present at 1 h after cell isolation but not detectable at 6 h; and P450(arom) and SMR mRNAs were first detectable at 6 h and 48 h, respectively. Incubation of cultures with insulin-like growth factor I (IGF-I, 10 ng/ml), dibutyryl cAMP (cAMP, 300 mu M), or their combination, induced measurable StAR mRNA at 24 h (p < 0.05), increased progesterone accumulation at 48 h, and elevated both SMR and P450(arom) expression through 96 h. Incubation of luteinized granulosa cells with epidermal growth factor (EGF, 10 nM) changed their phenotype from epithelioid to fibroblastic, eliminated steady-state StAR expression, and interfered with cAMP induction of StAR mRNA and progesterone accumulation. EGF had little apparent effect on P450(arom) mRNA abundance. It is concluded that SMR expression characterizes luteinization, and early luteinization is induced by cAMP and IGF-I in vitro. Further, EGF induces a morphological and functional phenotype that appears similar to an earlier stage of granulosa cell function.