Inhibin and premature ovarian failure

A. L. Chand, C. A. Harrison, A. N. Shelling

Research output: Contribution to journalReview ArticleResearchpeer-review

70 Citations (Scopus)

Abstract

Background: Elucidation of the causes of premature ovarian failure (POF) is difficult due to the heterogeneity of the condition. Inhibin is a potential candidate gene for POF based on its dual actions on FSH secretion by the pituitary and gametogenesis in the gonads. A missense mutation in the inhibin α subunit gene (INHA G769A) is associated with POF in several populations. However, there is phenotypic heterogeneity in INHA G769A mutation carriers. Methods: Relevant studies were identified by searching PubMed and mutational frequencies combined for meta-analysis. Results: Meta-analysis of published studies revealed a risk difference of 0.04 (-0.030 to 0.11). The occurrence of asymptomatic carriers in populations suggests incomplete penetrance and/or a multi-genetic cause of POF.We propose that a decline in inhibin bioactivity caused by the mutation could increase FSH levels; and in a susceptible individual, the heightened sensitivity to gonadotrophins causes POF. Impaired paracrine effects of inhibin could impact folliculogenesis due to reduced antagonism of activin, bone morphogenetic protein 15 and growth differentiation factor 9. Functional studies of this mutation indicate normal production of dimeric inhibin A and B and impaired bioactivity of inhibin B. Conclusions: The identification of an autosomal mutation in the inhibin a subunit gene that is significantly linked to POF in certain ethnic populations highlights the role of inhibin in the regulation of ovarian biology and fertility. Although the reduction of inhibin B bioactivity by the INHA G769A mutation is clearly not the only cause, evidence suggests that this change may serve as a susceptibility factor, increasing the likelihood of POF.

Original languageEnglish
Article numberdmp031
Pages (from-to)39-50
Number of pages12
JournalHuman Reproduction Update
Volume16
Issue number1
DOIs
Publication statusPublished - 14 Sep 2009
Externally publishedYes

Keywords

  • Inhibin
  • Inhibin A
  • Inhibin B
  • POF
  • Premature ovarian failure

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