Isoforms of Human Recombinant Follicle-Stimulating Hormone: Comparison of Effects on Murine Follicle Development In Vitro1

The effects of three isoforms derived from recombinant human FSH on ovarian follicle development in vitro were characterized for the first time. The three subfractions comprised discrete pI ranges of 3. 6-4.6 (acid), 4.5-5.0 (mid), and 5.0-5.6 (least acidic). Follicular growth, estradiol secretion, and antral formation were assessed for each fraction of isoforms in a range of concentrations over a 5-day culture period. Least acidic FSH produced, at and above 1.5 ng/ml, a high percentage of follicles growing above the size threshold necessary for antral formation, whereas mid and acid FSH induced similar growth only at higher concentrations (7.5 ng/ml and 50 ng/ml, respectively). Least acidic FSH specifically induced the most rapid growth of follicles during preantral development. Acid FSH at all concentrations stimulated estradiol-17ss secretion later during culture and antral formation in a lower proportion of follicles than did least acidic and mid FSH. It can be concluded 1) that the least acidic isoform induced fastest preantral growth, producing the largest antral follicles at the lowest dose of all three fractions and 2) that the less and mid acidic isoforms had more impact on stimulation of estradiol production and antral formation than the acid isoform.