Regulation of rat ovarian cell growth and steroid secretion

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Abstract
A cultured rat ovarian cell line (31A-F2) was used to study the effect of growth factors (epidermal growth factor [EGF] and fibroblast growth factor [FGF]), a survival factor (ovarian growth factor [OGF]), a hormone (insulin) and an iron-binding protein (transferrin) on cell proliferation and steroid production under defined culture conditions. EGF and insulin were mitogenic (half-maximal response at 0.12 nM and 0.11 .mu.M, respectively) for 31A-F2 cells incubated in serum-free medium. EGF induced up to 3 doublings in the cell population, whereas insulin induced an average of 1 cell population doubling. FGF, OGF and transferrin did not have any prominent effect on cell division when incubated individually with 31A-F2 cells in serum-free medium. A combination of EGF, OGF, insulin and transferrin stimulated cell division to the same approximate extent as cells incubated in the presence of 5% fetal calf serum. EGF or insulin did not significantly affect total cell cholesterol levels (relative to cells incubated in serum-free medium) when incubated individually with 31A-F2 cells. Cell cholesterol levels were increased by the addition of OGF (250%), FGF (370%) or a combination of insulin and EGF (320%). Progesterone secretion from 31A-F2 cells was enhanced by EGF (25%), FGF (80%) and insulin (115%). The addition of a mitogenic mixture of EGF, OGF, insulin and transferrin suppressed progesterone secretion 150% below that of control cultures. Apparently EGF and insulin are mitogenic factors that are required for the growth of 31A-F2 cells and OGF and transferrin are positive cofactors that enhance growth. Cholesterol and progesterone production in 31A-F2 cells apparently can be regulated by peptide growth factors and the hormone insulin.