Secretion of ovine luteinizing hormone in vitro: differential positive control by 17 beta-estradiol and a preparation of porcine ovarian inhibin.

17 beta-Estradiol (E2) and an enriched preparation of porcine ovarian inhibin can positively regulate LH secretion in two different ways in ovine pituitary cell cultures. One major effect of these agents is to increase the sensitivity of cultures to low levels of LHRH or LHRH analogs. The second effect is to increase culture responsiveness to high levels of LHRH or its analogs. Prolonged treatment with 1 nM E2, for instance, increased pituitary sensitivity to D-Lys6-LHRH by 10-fold, since it lowered the ED50 of D-Lys6-LHRH from approximately 400 pM to about 40 pM; the maximum LH secretory response to D-Lys6-LHRH (1-100 nM) was not changed, however. In contrast, short term treatment with an E2-free preparation of porcine ovarian inhibin could increase, by 350%, normal LH responsiveness to high levels of D-Lys6-LHRH (1-100 nM), but had no effect on sensitivity; the ED50 remained unchanged. Chronic treatment with inhibin eventually increased sensitivity, and interestingly, a short treatment with E2 (6 h) caused a major increase in both sensitivity and responsiveness, but the responsiveness component usually disappeared between 6 and 48 h of chronic E2 treatment. Treatment with both E2 and the inhibin preparation caused the greatest increase in pituitary sensitivity to D-Lys6-LHRH (ED50 decreased to approximately 30 pM), but the increased responsiveness to D-Lys6-LHRH (1-100 nM) declined with time as with E2-only treatment. The different actions of E2 and the ovarian inhibin preparation seen to perturb different aspects of LH secretion. Therefore, study of these phenomena may uncover novel molecular details governing LHRH-stimulated LH release. Furthermore, these two types of LH secretory control may be physiologically important, at least in sheep, and perhaps in other animals as well.