title: Human testicular germ cell tumours express inhibin subunits, activin receptors and follistatin mRNAs.
abstract: Germ cell development is influenced by activin and inhibin, which are produced by Sertoli cells. Activin also affects differentiation of mouse embryonal carcinoma cells, which, to a certain extent, resemble the embryonal carcinoma component of germ cell tumours. Therefore, the expression of inhibin/activin subunits, of activin receptors and of the activin-binding protein follistatin was studied in testicular germ cell tumours, using RNAase protection assays. Testicular germ cell tumours of adolescents and adults (TGCTs) and spermatocytic seminomas expressed activin type I and type II receptors (ActRI and ActRII respectively). 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 beta-subunit transcripts, which are a prerequisite for activin synthesis. Non-seminomas contained significantly higher levels of the inhibin betaA subunit (P<0.001) compared with seminomas. No activin betaC subunit transcripts could be demonstrated by RNAase protection. Inhibin alpha-subunit expression was absent in the spermatocytic seminomas, in six out of nine seminomas and in 10 out of 11 non-seminomas. Follistatin was expressed predominantly in non-seminomas and spermatocytic seminomas. This expression of activin type I and type II receptors in combination 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.
authors.affiliation: Department of Endocrinology & Reproduction, Erasmus University Rotterdam, The Netherlands.
authors.forename: R H
authors.initials: RH
authors.lastname: van Schaik
authors.forename: C D
authors.initials: CD
authors.lastname: Wierikx
authors.forename: L H
authors.initials: LH
authors.lastname: Looijenga
authors.forename: J W
authors.initials: JW
authors.lastname: Oosterhuis
authors.forename: F H
authors.initials: FH
authors.lastname: de Jong
mesh_terms: D029404:Activin Receptors; D030201:Activin Receptors, Type I; D038681:Follistatin; D018237:Germinoma / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D007265:Inhibins; D008297:Male; D010455:Peptides / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D029584:Prostatic Secretory Proteins; D012333:RNA, Messenger / Q000032:analysis; D017978:Receptors, Growth Factor / Q000378:metabolism*; D012044:Regression Analysis; D013736:Testicular Neoplasms / Q000378:metabolism*
chemical_list: D038681:Follistatin; D006023:Glycoproteins; D006133:Growth Substances; D010455:Peptides; D029584:Prostatic Secretory Proteins; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; C043076:beta-microseminoprotein; C094377:inhibin-alpha subunit; D007265:Inhibins; D029404:Activin Receptors; D030201:Activin Receptors, Type I