HUMAN TESTICULAR GERM-CELL TUMORS EXPRESS INHIBIN SUBUNITS, ACTIVIN RECEPTORS AND FOLLISTATIN MESSENGER-RNAS

Germ cell development is influenced by activin and inhibin, which are produced by Sertoli cells. Activin also affects differentiation of mou se embryonal carcinoma cells, which, to a certain extent, resemble the embryonal carcinoma component of germ cell tumours. Therefore, the ex pression of inhibin/activin subunits, of activin receptors and of the activin-binding protein follistatin was studied in testicular germ cel l tumours, using RNAase protection assays. Testicular germ cell tumour s of adolescents and adults (TGCTs) and spermatocytic seminomas expres sed activin type I and type II receptors (ActRI and ActRII respectivel y). Seminomas expressed significantly lower levels of ActRIIA (P<0.05, Mann-Whitney U-test) and higher levels of ActRIA (P<0.05) and ActRIB (P<0.05) compared with non-seminomas. All tumours expressed inhibin be ta-subunit transcripts, which are a prerequisite for activin synthesis . Non-seminomas contained significantly higher levels of the inhibin b eta A subunit (P<0.001) compared with seminomas. No activin beta C sub unit transcripts could be demonstrated by RNAase protection. Inhibin a lpha-subunit expression was absent in the spermatocytic seminomas, in six out of nine seminomas and in 10 out of 11 nonseminomas. Follistati n was expressed predominantly in non-seminomas and spermatocytic semin omas. This expression of activin type I and type [I receptors in combi nation with expression of inhibin beta-subunits indicates that activin may act as a para-or autocrine factor in the regulation of growth and differentiation of tumours of human germ cells.