INVIVO REGULATION OF FSH SYNTHESIS BY INHIBIN AND ACTIVIN

The effect of a single sc injection of the gonadal peptide, recombinant human activin A (rhActivin A), on gonadotropin synthesis and secretion was examined in adult and immature male and female rats and the effect of recombinant human inhibin A (rhInhibin A) was examined in adult male rats. Pituitary FSH-beta, LH-beta and alpha-messenger RNA (mRNA) levels were determined by blot hybridization. Trunk blood was collected to measure serum FSH levels. Treatment with rhInhibin A (100-mu-g/kg) resulted in a decrease in FSH-beta mRNA to 2% of controls levels 6 h after injection. FSH-beta mRNA levels started to rebound at 10 h, but were still significantly lower than vehicle-treated controls. Serum FSH levels were significantly reduced at 2 h and were reduced further at 6 and 10 h. There were no significant changes in alpha and LH-beta mRNA levels. RhActivin A, at the highest dose (500-mu-g/kg), in immature male rats had only a modest effect (1.2- and 1.3-fold increase) on FSH-beta mRNA levels and FSH secretion, respectively, at 2 h. No increase in FSH synthesis and FSH secretion was observed in adult male rats. In contrast, both immature and adult-ovariectomized E2 implanted females showed a robust response to rhActivin A. In immature females, 2 h after rhActivin A (100 and 500-mu-g/kg) administration, FSH-beta mRNA levels were elevated 2.0- and 2.2-fold. At this time serum FSH was also elevated. At 6 and 10 h rhActivin A significantly reduced FSH-beta mRNA levels from vehicle-treated controls. In contrast, FSH secretion was elevated at 6 h and returned to baseline at 10 h. Administration of rhActivin A (500-mu-g/kg) to adult, ovariectomized-E2 females resulted in a significant increase in FSH-beta mRNA levels and FSH secretion at 2 and 6 h. There were no significant changes in alpha and LH-beta mRNA levels in either males or females. Thus, these in vivo studies have shown that rhInhibin A can inhibit FSH-beta mRNA levels and FSH secretion in the adult male rat. RhActivin A stimulates FSH synthesis and secretion in the immature and adult ovariectomized-E2 females, but has little or no effect in immature and adult males. Hence, there is a sexual dimorphic response to rhActivin A in vivo in the rat.