Growth hormone as an amplifier of insulin-like growth factor-I action: potentiated oestradiol accumulation

Abstract

Abstract The interaction between GH and IGF-I in modulating oestradiol biosynthetic capacity was examined in cultured porcine granulosa cells. Granulosa cells (2 × 106 viable cells/culture) were initially cultured for 96 h (treatment period) in an androstenedione-free medium in the absence 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 and the cells were washed twice with the androstenedione-free medium and reincubated for an additional 24 h (test interval) in an androstenedione (10−7 m)-supplemented medium for oestradiol accumulation. GH alone induced no stimulation (P>0·05) of basal oestradiol accumulation. In contrast, concurrent treatment with IGF-I produced a 4·3-fold increase (26 vs 112 ng/2 × 106 cells per 24 h, P<0·001) in oestradiol accumulation. GH amplified IGF-I-induced oestradiol production in a dose (minimal dose requirement of 0·3 ng/ml)- and time (minimal time requirement of 24–48 h)-dependent manner. Studies on the site(s) of action indicated that GH exerts its amplifying effects on IGF-I-induced oestradiol production both proximal and distal to cAMP generation. As the specificity study and the inhibitory study indicated, GH amplification of IGF-I-induced oestradiol production is a process involving gene transcription 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 of GH. Journal of Endocrinology (1997) 152, 201–209