Gonadotropin binding and stimulation of steroidogenesis in Leydig tumor cells.
Testicular tumors are generally characterized by a loss of responsiveness to gonadotropins. The M5480 Leydig cell tumor is unusual, if not unique, in that it responds to human choriogonadotropin and to lutropin via increased steroidogenesis. This report describes the identification of two variants of the original M5480 tumor that have altered steroid output both in the basal state and in response to human choriogonadotropin. One of the tumors produces mainly progesterone, which is stimulated by the choriogonadotropin; the other tumor produces about equal amounts of progesterone and testosterone, and the secretion of both is stimulated by the choriogonadotropin. The dissociation constant describing the interaction between Leydig tumor cells and (125)I-labeled human choriogonadotropin is between 3 and 5x10(-11) M. This agrees with values reported for normal Leydig cells, although the tumor cells appear to have fewer receptors. The differences noted in the two tumors and normal Leydig cells may have arisen from alterations in gene regulation, or in mutations, involving one or more enzymes in the pathway in which progesterone is converted to testosterone. Under the experimental conditions used, all the tumors studied (seven generations) responded to the choriogonadotropin both in binding and in the resultant stimulation of steroidogenesis. This property, together with the characteristic that a homogeneous cell population can be obtained without enzymatic treatment, should qualify the M5480 Leydig cell tumor(s) as a model system for further studies on the mechanism of action of gonadotropin, on hormone receptors, and on hormonally responsive tumors.
D000818:Animals; D006063:Chorionic Gonadotropin / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D007984:Leydig Cell Tumor / Q000378:metabolism*; D007985:Leydig Cells / Q000378:metabolism; D008297:Male; D051379:Mice; D009374:Neoplasms, Experimental / Q000378:metabolism; D011374:Progesterone / Q000096:biosynthesis*; D011956:Receptors, Cell Surface / Q000378:metabolism; D013736:Testicular Neoplasms / Q000378:metabolism*; D013739:Testosterone / Q000096:biosynthesis*
D006063:Chorionic Gonadotropin; D011956:Receptors, Cell Surface; D013739:Testosterone; D011374:Progesterone