Serum FSH-suppressing activity of human recombinant inhibin A in male and female rats

Abstract

After a single i.v. injection of purified human recombinant inhibin A (hr-inhibin) or bovine follicular fluid (bFF) to 3-day castrated 35-day-old male rats, serum FSH concentrations fell (P < 0.05) between 4 and 8 h, returning to control concentrations by 16-24 h. Administration of graded doses of hr-inhibin (0.625-10 μg/100 g body wt) and bFF (31.3-250 μl/100 g body wt) resulted in a parallel dose-related suppression of serum FSH with a maximum suppression 50% of controls. Similar experiments in 2-day ovariectomized 85-day-old female rats also showed a dose-related suppression with a maximum suppression approximately 30% of controls. Serum LH concentrations remained unchanged in all studies with male or female rats. The biological activity of hr-inhibin in vivo was determined for male and female rats in terms of a standard bFF preparation defined by an in-vitro bioassay based on the suppression of FSH content in rat pituitary cells in culture. In males hr-inhibin exhibited a biopotency of 407 (159:1050; fiducial limits) U/μg protein and in females the biopotency was 358 (226:565) U/μg protein. These potencies are lower than that measured in the in-vitro bioassay (1120 (1040:1210) U/μg protein) and differences between in-vivo and in-vitro systems were attributed to the use of bFF rather than a purified human inhibin preparation as standard. These results indicate that hr-inhibin behaves similarly in vivo to bFF. Furthermore, based on the large working range and relatively good precision, the female rat system provides a good basis for an inhibin in-vivo bioassay method.