The mechanism for the onset of puberty in Familial Male Precocious Puberty (FMPP) has never been understood. It is a gonadotropin independent form of puberty and no bioactive substance could be identified in the plasma of these boys using a rat testicular model. We developed a unique bioassay model using intact cynomolgus monkeys that had been pretreated with a LHRH antagonist to remove their endogenous gonadotropins. In this model, we were able to demonstrate that infusion of plasma from a boy with FMPP into the testicular artery caused a significantly greater testosterone response than infusion of plasma from a prepubertal control. Now that we have demonstrated the presence of this factor, we developed an in vitro system to isolate the factor. The system which shows the greatest promise is a mouse Leydig cell tumor line which responds to cAMP but not to gonadotropins. When plasma from boys with FMPP is placed in the media, there is greater hormone plasma from production than when plasma from prepubertal boys is placed in the media. Normal adult males have an intermediate response. At present, we are refining the techniques and con- tinuing to collect plasma from boys with FMPP being studied by the investigators in DEB/NICHD.
