EFFECT OF RECOMBINANT INHIBIN ON LUTEINIZING-HORMONE AND FOLLICLE-STIMULATING-HORMONE SECRETION IN THE RAT

We investigated the effect of the iv injection of recombinant human (rh) inhibin on FSH and LH secretion in the female rat under various experimental circumstances. Rh inhibin caused dose-related decreases in mean plasma FSH, but not LH, levels in ovariectomized female rats 14 days old and older. The duration of this inhibition was proportional to the dose of rh inhibin, but no consistent changes in FSH secretion were observed until 4 h after treatment. Maximum suppression of FSH release was observed at about 15-mu-g rh inhibin/kg BW and lasted 8-10 h. Measurement of the area under the curve from 4-12 h after injection of inhibin indicated a dose-related decrease in total FSH secreted. When blood samples were withdrawn every 10 min to evaluate pulsatile gonadotropin release, analysis of FSH pulse parameters indicated that rh inhibin (25-mu-g/kg) interfered with pulse frequency, amplitude, and peak levels in both intact and ovariectomized rats. In contrast, pulsatile LH secretion was not measurably altered. These results demonstrate that rh inhibin acts primarily at the level of the pituitary to inhibit all parameters of FSH secretion and suggest that this effect is at least not entirely mediated by changes in GnRH receptors.