Hormone synthesis and responsiveness of spontaneous granulosa cell tumors in (SWR x SWXJ-9) F1 mice

Granulosa cell tumors spontaneously occur in approximately 10-25% of female (SWR x SWXJ-9) F1 mice. The present studies were designed to test whether tumor-bearing mice produce a distinct hormonal profile by which they could be identified and determine whether cultured tumor cells are responsive to hormones and growth factors that regulate normal granulosa cells. Samples of female mouse blood taken from age 3 to 10 weeks allowed estimation of serum FSH, 17 beta-estradiol, and inhibin levels for normal mice and for mice destined to develop tumors. These studies indicated that FSH and 17 beta-estradiol values differed between normal and tumor-bearing animals, but overlapped sufficiently that such values could not accurately predict the tumor-bearing state. Inhibin concentrations did differentiate normal from tumor-bearing animals in all cases. Increased levels of inhibin were observed coincident in time with visibly detectable tumors within the ovaries. Compared to inhibin synthesis in vivo, hormonal responsiveness in vitro was much more variable. Steroidogenesis was stimulated in all tumors by dibutyryl-cAMP and low-density lipoprotein (LDL). Some, but not all, tumors responded to IGF(1), EGF, FSH, and hCG. In about one-half of the tumors tested, FSH could induce hCG or dibutyryl-cAMP responsiveness. IGF(1) pretreatment consistently increased the responsiveness of tumor cells stimulated by dibutyryl-cAMP and LDL. Production of inhibin by isolated tumor cells was detectable and decreased by EGF or dibutyryl-cAMP treatments. We conclude that granulosa tumor cell secretion of inhibin may be under different control than secretion from normal granulosa cells and acts as an excellent marker for these tumors. (C) 1997 Academic Press.