GROWTH-HORMONE AS AN AMPLIFIER OF INSULIN-LIKE GROWTH-FACTOR-I ACTION- POTENTIATED ESTRADIOL ACCUMULATION

The interaction between GH and IGF-I in modulating oestradiol biosynth etic capacity was examined in cultured porcine granulosa cells. Granul osa cells (2 x 10(6) viable cells/culture) were initially cultured for 96 h (treatment period) in an androstenedione-free medium in the abse nce or presence of IGF-I (0 or 50 ng/ml), with or without GH at 100 ng /ml. At the conclusion of this period, culture media were discarded an d the cells were washed twice with the androstenedione-free medium and reincubated for an additional 24 h (test interval) in an androstenedi one (10(-7) M)-supplemented medium for oestradiol accumulation. GH alo ne induced no stimulation (P>0.05) of basal oestradiol accumulation. I n contrast, concurrent treatment with IGF-I produced a 4.3-fold increa se (26 vs 112 ng/ 2 x 10(6) cells per 24 h, P<0.001) in oestradiol acc umulation. GH amplified IGF-I-induced oestradiol production in a dose (minimal dose requirement of 0.3 ng/ml)- and time (minimal time requir ement of 24-48 h)-dependent manner. Studies on the site(s) of action i ndicated that GH exerts its amplifying effects on IGF-I-induced oestra diol production both proximal and distal to cAMP generation. As the sp ecificity study and the inhibitory study indicated, GH amplification o f IGF-I-induced oestradiol production is a process involving gene tran scription and/or translation and the synergism is not solely specific to IGF-I as IGF-II-induced oestradiol production was also amplified in the presence oi GH.