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Acidic Mix of FSH Isoforms Are Better Facilitators of Ovarian Follicular Maturation and E2 Production than the Less Acidic

Department of Pediatrics (V.P., J.S.L.), Biostatistics (N.E.C., W.Y.), and the Reproductive Sciences Program (C.R.W., T.P.S., V.P.), University of Michigan, Ann Arbor, Michigan 48109; and Medical Research Council Human Reproductive Sciences Unit (A.S.M.), Edinburgh, Scotland EH3 9ET, United Kingdom

Address all correspondence and requests for reprints to: Vasantha Padmanabhan, Reproductive Sciences Program, 300 North Ingalls Building, Room 1109 SW, Ann Arbor, Michigan 48109-0404. E-mail: vasantha{at}umich.edu

FSH is secreted as a mix of isoforms with varying biologic attributes. To determine the functional significance of FSH heterogeneity, an acidic (ovine pituitary FSH; C-FSH) and less acidic mix (C-FSH exposed to neuraminidase; N-FSH) were administered to prepubertal lambs. Production of GnRH- induced less acidic FSH was blocked with a competitive GnRH receptor antagonist, Nal-Glu. Beginning 24 h after Nal-Glu, lambs were injected with C-FSH or N-FSH and LH. Controls included untreated, GnRH-treated, and Nal-Glu-treated groups. Blood samples were obtained at 2-h intervals. Plasma FSH levels were similar before treatment and increased over time in the C-FSH but not the N-FSH group (P < 0.001). Three of the six GnRH-treated ewes exhibited an LH surge. Peak E2 concentrations in the GnRH-treated animals were achieved 30–36 h after initiation of treatment. Peak circulating E2 levels tended to be higher in the C-FSH than in the GnRH-treated group. Only two of six N-FSH-treated ewes had a serum E2 rise. The C-FSH ewes had more estrogenic follicles than the GnRH and N-FSH groups (P < 0.05). Our findings show that C-FSH clears more slowly than N-FSH, and C-FSH is a better facilitator of follicular development and maturation than N-FSH.

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