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Roles of inhibin A and B in reproductive system
Summary
Inhibin A and inhibin B, members of the TGFβ family, are essential regulatory factors in mammalian reproduction. This research aims to determine their mechanisms of action.
Description
Inhibins, heterodimers of related alpha-and beta-subunits, antagonise the actions of TGF-beta ligands that utilise activin type II receptors as part of their signalling complex. Inhibin A and inhibin B negatively regulate the production and secretion of follicle stimulating hormone (FSH) from the anterior pituitary, control intragonadal events including ovarian follicle development and steroidogenesis, and act as tumor suppressors in the gonads and adrenal cortex. The expression patterns of the inhibin isoforms are sexually, spatially and temporally dimorphic suggesting that inhibin A and B may be functionally or mechanistically distinct.
The implications for reproductive physiology and pathophysiology of a distinct inhibin B mechanism of action are significant. It would identify potential molecular targets for the development of therapeutic means for modulating fertility.
In addition, an understanding of the mechanisms involved in inhibin A and B actions will enhance the management and monitoring of reproductive disorders and possibly identify biomarkers with improved sensitivity and specificity.
Funding
National Health and Medical Research Council
Outcomes
2008 - Craig Harrison presented findings at the US Endocrine Society meeting
Selected Publications
Makanji, Y., Walton, K., Wilce, M., Chan, K., Robertson, D. & Harrison, C.A. (2008) Suppression of inhibin A biological activity by alterations in the binding site for betaglycan. J Biol Chem 2008 Jun 13;283(24):16743-51
Makanji, Y., Harrison, C.A., Stanton, P.G., Krishna. R., and Robertson, D.M. Inhibin A and B in vitro bioactivities are modified by their degree of glycosylation and their affinity to betaglycan. Endocrinology, 2007 148(5):2309-2316
Harrison, C.A., Wiater, E., Lewis, K.A., Gray, P.C., and Vale, W.W. Identification of distinct inhibin and TGFbeta binding sites on betaglycan: functional separation of betaglycan co-receptor actions. J Biol Chem, 2006. 281:17011-22.