Effect of aromatase inhibitor (fadrozole) on proliferation, estradiol production and telomerase activity in pig granulosa cells in vitro

The objective of the present work was to study the effect of a nonsteroidal aromatase inhibitor (fadrozole) on proliferation, estradiol production, aromatase expression and telomerase activity (TA) in pig granulosa cells (GC) from small (1-2 mm) and large (5-7 mm) follicles. The cells were treated with fadrozole for 48 h and 72 h in basal and FSH-stimulated conditions. Fadrozole caused a decrease (P < 0.05) of 3H-thymidine incorporation in granulosa cells derived from small (1-2 mm) and large follicles (5-7 mm). The proliferative potential of small-follicle GC was significantly higher (P < 0.01) under all culture conditions. Estradiol production was suppressed (P < 0.01) in both granulosa cell populations cultured in the presence of fadrozole for 48 and 72 h. Fadrozole caused a decrease (P < 0.05) of aromatase gene expression in small-follicle granulosa cell incubated for 72 h and in large-follicle GC after 48 h of culture. Large-follicle GC were characterized by a higher (P < 0.01) level of estradiol production and aromatase gene expression. Telomerase activity decreased (P < 0.05) in large-follicle granulosa cells incubated in the presence of an aromatase inhibitor for 72 h. The TA level in large-follicle granulosa cells was higher (P < 0.01) in comparison to small-follicle GC in all culture conditions after 72 h of incubation. The results of the present study suggest the important role of telomerase in the process of follicular growth and development.