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Inhibin B Is a More Potent Suppressor of Rat Follicle-Stimulating Hormone Release than Inhibin A in Vitro and in Vivo

Prince Henry’s Institute of Medical Research (Y.M., K.L.W., C.A.H., D.M.R.), Department of Obstetrics and Gynecology (Y.M., D.M.R.), and Monash Institute of Medical Research (P.D.T.-S.), Monash University, Clayton, Victoria 3168, Australia

Address all correspondence and requests for reprints to: Yogeshwar Makanji, Prince Henry’s Institute of Medical Research, 246 Clayton Road, Clayton, Victoria 3168, Australia. E-mail: yogeshwar.makanji{at}princehenrys.org.

Mature 31- and 34-kDa inhibin A and B negatively regulate the release of FSH from the anterior pituitary; however, a direct comparison of these hormones in vivo has not been undertaken. The bioactivities of highly purified preparations of recombinant human 31-kDa inhibin A and B were determined in rat pituitary cells in vitro, and in ovariectomized adult rats in vivo based on suppression of plasma FSH. The 31-kDa inhibin B was 4.2-fold more bioactive than inhibin A in vitro and 1.45 (1.01–2.79)-fold more bioactive in vivo than 31-kDa inhibin A. However, the corresponding relative binding affinities of 31-kDa inhibin B for betaglycan, betaglycan+activin type II receptor (ActRII)-A, and betaglycan+ActRIIB were lower (IC₅₀ 2200, 400, and 750 pM, respectively) compared with 31-kDa inhibin A (IC₅₀ 190, 80, and 290 pM, respectively). A 2.7- and 2.5-fold reduction in in vitro bioactivity was observed between the 31- and 34-kDa inhibin A and 31- and 34-kDa inhibin B, respectively, and these decreases in bioactivities were matched by a parallel reduction in binding to betaglycan and betaglycan+ActRIIA/B. It is concluded that the increased in vitro and in vivo bioactivities of 31-kDa inhibin B cannot be explained by a higher affinity to betaglycan or activin type II receptors; thus, additional factors mediate inhibin B’s action. In addition, similar reductions in in vitro bioactivity and betaglycan+ActRIIA/B binding between 31- and 34-kDa inhibins A and B are attributed to hindrance by the additional carbohydrate group at Asn³⁰² in the formation of a functional inhibin+betaglycan+ActRIIA/B complex.