Progestogen regulation of tissue plasminogen activator in a human melanoma cell line

The influence of progestogens, i.e. medroxyprogesterone, levonorgestrel and norethisterone, was studied in a melanoma cell line producing tissue-type plasminogen activator (t-PA). The cell cultures were exposed to the three progestogens by addition of the steroids dissolved in a weak alcoholic solution to the culture media, in which the released t-PA was assayed by an immunoradiometric method. Ethanol (0.76% w/v) stimulated the t-PA production, while significant inhibitory effect of the present progestogens in the concentration of 1.7 x 10(-6) M was recorded. By tenfold decrease in progestogen concentration significant reduction of t-PA levels was still seen in the cultures exposed to levonorgestrel, while medroxyprogesterone and norethisterone in this dose had no effect on t-PA release. Norethisterone differed from the other two progestogens in having weak toxic effect on melanoma cells. It was concluded that the progestogens studied, in particular norethisterone and levonorgestrel, had an inhibitory effect on the production of t-PA in melanoma cell culture.