Effects of 31 kilodalton bovine inhibin on follicle-stimulating hormone and luteinizing hormone in rat pituitary cells in vitro: actions under basal conditions.

The effects of purified 31 kilodalton (kDa) bovine inhibin on the basal release and cell contents of FSH and LH in pituitary cells from adult male Sprague-Dawley rats have been investigated for periods up to 28 days in tissue culture. A constant rate of basal FSH release (1.90 +/- 0.24 ng/10(6) cells.h) was observed during the first 10 days of culture and this release was blocked by inhibin in a concentration-dependent manner (IC50 = 0.16 U/ml, IC100 greater than 2.5 U/ml). The constant basal LH release between days 2 and 12 of culture (0.15 +/- 0.02 ng/10(6) cells.h) was also blocked by inhibin in a concentration-dependent manner to a minimum of 25% of control (IC50 = 0.66 U/ml, ICmax greater than 6 U/ml). FSH and LH cell contents decreased exponentially in the presence and absence of inhibin over the first 20 days of culture permitting the calculation of decay half-times (t1/2). Inhibin reduced the FSH cell content t1/2 from 5.0 to 1.8 days and the LH cell content t1/2 from 5.8 to 3.6 days (IC50 = 0.81-0.83 U/ml, ICmax greater than 6 U/ml for both FSH and LH). The sum of the FSH released and FSH cell content (i.e. total FSH) increased with time in culture and this increase was blocked by inhibin. In contrast, total LH decreased with time in all cultures. The data suggest that in pituitary cells separated from hypothalamic and gonadal inputs 1) inhibin primarily suppresses tonic FSH synthesis coupled to its basal release; 2) at higher concentrations inhibin partially suppresses basal LH release and promotes intracellular degradation of FSH and LH. Thus, based on differences in sensitivity, inhibin acts at two or more sites, one associated with FSH tonic synthesis-basal release and the other(s) with FSH/LH mobilization and/or degradation.