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-Subunit Promoter/Simian Virus 40 T-Antigen Fusion Gene
Department of Physiology University of Turku 20520 Turku, Finland
Transgenic (TG) mice, expressing the Simian Virus
40 T-antigen (Tag) under a 6-kb fragment of the murine inhibin
-subunit promoter (inhp), develop gonadal tumors of
granulosa/theca or Leydig cell origin. We showed previously that
adrenocortical tumors develop if the TG mice are gonadectomized but
never develop in intact animals. However, if functional gonadectomy was
induced by GnRH antagonist treatment or by cross-breeding the TG mice
into the hypogonadotropic hpg genetic background,
neither gonadal nor adrenal tumors appeared. Since the most obvious
difference between the gonadectomized and GnRH-antagonist-treated or
Tag/hpg double mutant mice is the elevated
gonadotropin secretion in the first group, we examined whether the
adrenal tumorigenesis would be gonadotropin-dependent. Surprisingly,
both the adrenal tumors and a cell line (C1) derived from one of
them expressed highly functional LH receptors (LHR), as assessed by
Northern hybridization, immunocytochemistry, ligand binding, and human
CG (hCG)-stimulated cAMP and steroid production. No FSH receptor
expression was found in the adrenal tumors by RT-PCR. hCG treatment of
the C1 cells stimulated their proliferation, as measured by
[3H]thymidine incorporation. This
effect was related to hCG-stimulated steroidogenesis since
progesterone, testosterone, and estradiol, at physiological
concentrations, also stimulated the C1 cell proliferation. Different
adrenocortical cells expressed initially LHR and Tag, whereas both were
highly expressed in the tumor cells. In conclusion, the high level of
functional LHR in the adrenal tumors indicates that this receptor can
function as tumor promoter when ectopically expressed and stimulated by
the ligand hormone.
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