In an attempt to determine the susceptibility of spermatogonia to malignant transformation transgenic mice were generated harboring a 1.3 kb 5'-flanking region of the germ cell specific expressed human testis specific protein, Y-encoded gene fused with the simian virus 40 large T antigen (TAg). Unexpectedly, TAg expression in transgenic mice was also detected in somatic tissues. Between days 65 and 85 after birth most of the transgenic mice developed anterior lobe tumors of the pituitary gland and to a less extent medulla type tumors of the adrenal gland. In addition, a few older transgenic mice developed tumors of the seminal vesicle, but no testicular tumors were observed in transgenic mice up to an age of 5 months. The pituitary tumors were immunoreactive for anti-prolactin (PRL) and anti-adrenocorticotropic hormone (ACTH). PRL and corticosterone concentrations in serum of transgenic mice were significantly increased. Taken together, our studies provide a novel mouse model for pituitary adenomas displaying a unique combination of hormone expression by tumor cells secreting PRL and ACTH.