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Meningiomas have been hypothesized as being hormonally sensitive on the basis of epidemiologic, clinical, and laboratory evidence. Eight meningiomas were assayed and found to have androgen-binding protein. Three tumors were subjected to in vitro growth studies in varying concentrations of dihydrotestosterone (DHT). The growth of tumor 1 was unaltered. Tumor 2 demonstrated 9% to 10% growth (P less than 0.05) in all concentrations tested. Tumor 3 revealed an 11% stimulation, but only in the lowest concentration of DHT tested. The small quantity, saturability, and in one tumor, high binding affinity, suggest this binding protein is a receptor. The in vitro response of these meningiomas was small and was not dose-related or proportionate to receptor quantity. Androgens do not appear to play as important a role as progesterone or estrogen in meningioma growth in vitro.

Speculation that meningiomas are subject to endocrine influence is supported by their higher incidence in women, reports of exacerbation of symptoms during pregnancy, and the discovery that these tumors harbor progesterone- and estrogen-binding proteins. To evaluate if these properties could be exploited therapeutically, specimens from three convexity meningiomas were used for estrogen- and progesterone-binding protein assays and establishment of tissue cultures. Each tumor (designated A, B, and C, respectively) was grown in experimental media containing 7.5 X 10(-5) to 10(-12) M 17 beta-estradiol, 2.5 X 10(-4) to 10(-12) M progesterone, 10(-7) to 10(-9) M tamoxifen (an estrogen antagonist), and 10(-6) to 10(-10) M RU486 (a progesterone antagonist). After incubation, cell growth was compared to control preparations by counting the meningioma cells present in each medium. Tumors A, B, and C contained estrogen-binding proteins of 8.45, 13.6, and 26.9 fmol/mg cytosol protein and progesterone-binding proteins of 210, 130, and 126 fmol/mg cytosol protein, respectively. The media containing 17 beta-estradiol and progesterone caused 21% to 36% growth stimulation in Tumors A and B. In Tumor A, the addition of tamoxifen stimulated growth by 35%, while it caused only transient stimulation in Tumor B and had no effect on Tumor C. RU486, the progesterone antagonist, caused inhibition of cell growth in all three tumors, ranging from 18% to 36%. These data suggest that selected meningiomas are subject to hormonal influence in vitro. The inhibition of meningioma growth in vitro by the antiprogesterone, RU486, has not been previously reported, and serves to encourage further development of alternative modes of therapy for recurrent and unresectable meningiomas.

Meningiomas have been shown to have steroid-binding proteins. In vitro, estradiol, progesterone, and the antiestrogen tamoxifen stimulate tumor growth. However, incubation of tumor cells with an antiprogesterone agent results in tumor inhibition. In this investigation, a human meningioma was implanted subcutaneously in athymic nude mice. Two treatment groups were established, one receiving the antiprogesterone agent RU-38486 (10 mg/kg/day in suspension) and the other receiving only vehicle. After 3 months, the tumor growth index (defined as the tumor volume at 3 months divided by the initial tumor volume) was 0.25 +/- 0.46 (mean +/- standard deviation) in the group receiving antiprogesterone and was 1.54 +/- 0.58 in the control group (p = 0.041). Further investigation of the effect of antiprogestational agents on the growth and hormone-binding proteins of other meningiomas will better define the mechanism of their effects.