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Submitted on December 1, 2006
Accepted on January 19, 2007
Prince Henry's Institute of Medical Research, Clayton, Victoria 3168, Australia; Monash University, Department of Obstetrics and Gynaecology, Clayton, Victoria 3168, Australia; DSL-Beckman Coulter, Webster, Texas, USA
* To whom correspondence should be addressed. E-mail: david.robertson{at}princehenrys.org.
Inhibin A and B, important regulators of normal function in tissues of the reproductive axis, are either glycosylated at Asn268 or Asn268 and Asn302 in the 
subunit to produce 31 and 34k isoforms, respectively. In this study, glycosylated isoforms of recombinant human inhibin A and B were purified from conditioned medium using immunoaffinity chromatography and RP-HPLC. The masses of the purified inhibin preparations were determined by several inhibin immunoassays and their in vitro bioactivities were based on suppression of FSH release by rat pituitary cells in culture. Based on a ratio of in vitro bioactivity to immunoactivity (B:I ratio), the monoglycosylated 31k inhibin A was 5-fold more potent than the diglycosylated 34k inhibin A (B:I ratio 1.22±0.15 vs 0.24±0.05, p<0.001, respectively). The 31k inhibin B was significantly (p<0.001) more potent (1.75±0.29) than the 34k form (1.08±0.20). As inhibin biological activity is dependent upon interactions with the co-receptor betaglycan, the effect of inhibin glycosylation on betaglycan binding was assessed. Analogous to the pattern of in vitro bioactivity, 31k inhibin A was 12-fold more active (IC50-0.68 nM) than the 34k isoform (IC50-8.2 nM) at displacing [125I]-inhibin A from COS7 cells expressing betaglycan. However, the 1.6-fold difference in bioactivity of the inhibin B isoforms was not matched by differences in their affinities for betaglycan. It is concluded that glycosylation of Asn302 of the subunit of inhibin A and B results in a decrease in bioactivity, the effect on inhibin A, at least, is explained by its reduced affinity to betaglycan.
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