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Contributor Information

  • Name Craig Harrison
  • Institute Hudson Institute of Medical Research

Tool Details

  • Tool name: Mutant Inhibin A
  • Alternate names: Follicle-stimulating hormone, FSH, activin, Transforming growth factor beta, TGF-?, Down's Syndrome,
  • Tool type: Proteins
  • Tool sub-type: Recombinant Peptide
  • Cancer type: Ovarian
  • Expression system: Recombinant
  • Description: Inhibin is a member of the TGF-? subunit superfamily, formed from heterodimeric complexes composed of a-subunit and ?-subunits, in comparison to the majority of the other family members, which are homodimers. Inhibin acts as an antagonist inhibiting signalling of activin-related proteins (functioning in an endocrine rather than autocrine/paracrine manner). It regulates follicle-stimulating hormone (FSH) secretion from the anterior pituitary by blocking actions of activins. Inhibins are a non-steroidal gonadal hormone, best characterised for their role in regulating reproductive function. Recent research suggests that inhibins have pleiotropic actions, and are expressed in many organ systems throughout the body. Of particular interest, inhibin has been shown to stimulate bone growth, leading to suggestions of its potential as a therapeutic for osteoporosis. Inhibin A and Inhibin B are heterodimers, made up of an a-subunit linked to a ?-subunit. Two ?-subunits linked together forms activin, a protein with often opposing actions to inhibin. Overexpression of inhibin also results in expression of activin, and separating the two proteins is extremely challenging. The inability to produce stable and purified active recombinant inhibin has hindered studies into its potential use as a therapeutic agent or diagnostic tool. The present invention relates to the recombinant production of inhibin. At least one proprotein convertase cleavage site of the precursor subunits of inhibin is modified through substitution with the more efficiently processed cleavage site ISSRKKRSVSS. Further modifications include mutation of the type I receptor (ALK4) binding epitope of the beta subunit to supress activin bioactivity, and mutation of the homodimerization interface site of the beta subunit to reduce or prevent activin formation. Also disclosed are pharmaceuticals and uses of the inhibin precursor and mature inhibin. Inhibin stimulates bone mass and strength and is known to be decreased in post-menopausal women suffering osteoporosis. Its full potential is yet to be realized, as production of this protein at scale is extremely challenging.
  • Research area: Developmental Biology ; Drug Discovery & Development ; Reproductive Biology

  • For Research Use Only

Target Details

Application Details

Handling

  • Shipping conditions: Dry Ice

Documentation

  • Available on request

References

  •   Bernard et al. 2016. Endocrinology. 157(7):2583-5. PMID: 27363870.
  •   Walton et al. 2016. Endocrinology. 157(7):2799-809. PMID: 27054553.
  •   Disinhibiting an Inhibitor: Genetic Engineering Leads to Improvements in Recombinant Inhibin A Production.
  •   A Novel, More Efficient Approach to Generate Bioactive Inhibins.