Androgen responsiveness of the pituitary gonadotrope cell line L beta T2

Androgens have a profound effect on the hypothalamic-pituitary axis by redu cing the synthesis and release of the pituitary gonadotropin LH. The effect on LH is partly a , consequence of a direct, steroid-dependent action on p ituitary function. Although androgen action has been well studied in vivo, in vitro cell models of androgen action on pituitary gonadotropes have been scarce. Recently, an LH-expressing cell line, L beta T2, was generated by tumorigenesis targeted to the LH-producing cells of the mouse pituitary. Th e purpose of these studies was to determine the presence of androgen recept or (AR) and establish its function in this cell line. RT-PCR analysis indic ated that the L beta T2 cell line expresses AR mRNA. Transient transfection assays, using the mouse mammary tumor virus (MMTV) promoter, showed that a functional AR is also present. Testosterone (TEST), dihydrotestosterone (D HT), 7 alpha -methyl-19-nortestosterone (M-ENT), and fluoxymesterone (FLUOX Y) increased reporter gene activity in the rank order of potencies MENT > D HT > TEST > FLUOXY. Additionally, activation of MMTV promoter activity by D HT in L beta T2 cells was diminished by the AR antagonists casodex and 2-hy droxy-flutamide, indicating that the effects of DHT are mediated through AR . In summary, these studies showed that the L beta T2 cell line is a useful model for the evaluation and molecular characterization of androgen action in pituitary gonadotropes.