In vitro secretion of FSH by cultured clinically nonfunctioning and gonadotroph pituitary adenomas is directly correlated with locally produced levels of activin A

OBJECTIVE Expression of mRNAs encoding activin and its antagonists inhibin and follistatin has been described in human pituitary adenomas, including c linically nonfunctioning adenomas (NFAs) and gonadotroph adenomas (Gn-omas) . Since many of the NFAs and Gn-omas secrete FSH in vitro, we hypothesized that locally produced activin may stimulate secretion of FSH in these pitui tary adenomas. PATIENTS and METHODS Pituitary adenoma tissue was obtained from 38 patients diagnosed preoperatively as having NFAs (n = 17), Gn-omas (n = 5), prolact inomas (n = 6) or growth hormone (GH) producing adenomas (n = 10), Actual p rotein levels of activin, inhibin, follistatin, FSH and LH were measured in media of these 38 cultured pituitary adenomas. In addition, we investigate d correlations between concentrations of these growth factors and hormones in NFAs and Gn-omas. RESULTS Gn-omas were found to secrete significantly more activin A In their culture medium than PRL- and GH-producing adenomas (P < 0.05). Inhibin A a nd inhibin B protein levels in culture media were very low. A positive corr elation between levels of activin A and FSH (r = 0.56, P < 0.005) was found , while no correlation between activin A and LH could be detected. Furtherm ore, levels of follistatin were positively correlated with activin A levels (r = 0.73, P < 0.0005). Comparison of the activin A:follistatin ratio with the measured FSH protein levels showed an evert stronger relationship (r = 0.79, P < 0.0005). CONCLUSIONS It is concluded that revels of activin A, follistatin and FSH i n media of cultured nonfunctioning adenomas and gonadotroph adenomas are po sitively correlated. This suggests that these adenomas secrete FSH in respo nse to the relatively high locally produced levels of activin A.