Inhibin B is a more potent suppressor of rat follicle-stimulating hormone release than inhibin a in vitro and in vivo.
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 (IC(50) 2200, 400, and 750 pm, respectively) compared with 31-kDa inhibin A (IC(50) 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 Asn(302) in the formation of a functional inhibin+betaglycan+ActRIIA/B complex.
Makanji
Yogeshwar
Y
Department of Obstetrics and Gynecology, Prince Henry's Institute of Medical Research, Clayton, Victoria 3168, Australia. yogeshwar.makanji@princehenrys.org
Temple-Smith
Peter D
PD
Walton
Kelly L
KL
Harrison
Craig A
CA
Robertson
David M
DM
D030301:Activin Receptors, Type II / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood*; D052681:Gonadotrophs / Q000378:metabolism; D006801:Humans; D007265:Inhibins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009154:Mutation; D020033:Protein Isoforms / Q000737:chemistry; D011509:Proteoglycans / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*
D020033:Protein Isoforms; D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; C422362:inhibin A; C422364:inhibin B; C071736:betaglycan; D007265:Inhibins; D005640:Follicle Stimulating Hormone; D030301:Activin Receptors, Type II