BACKGROUND:Premature ovarian failure (POF) is characterized by hypergonadotropic amenorrhoea before the age of 40. Inhibin alpha-subunit (INHalpha) gene is proposed as a candidate gene due to its role in negative feedback control of FSH. METHODS:Polymorphism -16C>T of INHalpha gene was studied in 61 POF patients and 82 controls above 40 years old (C > 40). Substitution 769G>A was studied in 59 POF patients, 76 C > 40 and 73 controls below 40 years old (C < 40). RESULTS:No significant difference in risk of POF development for -16T allele was found when comparing idiopathic POF (I-POF) with C > 40 (Odds ratio = 1.46; 95% confidence interval = 0.63-3.19). Implication of -16C>T polymorphism in serum inhibin levels was analysed in 46 controls, and no significant differences (P > 0.05) were found between CC and CT + TT genotype groups when comparing either mid-follicular phase Pro-alphaC and inhibin B values or mid-luteal phase Pro-alphaC and inhibin A values. Heterozygosity for substitution 769G>A was found in 1 of 59 POF woman, 2 of 76 C > 40 and 6 of 73 C < 40. Presence of this substitution in a relevant number of control subjects is herein described for the first time. CONCLUSION:Our results indicate that -16C>T and 769G>A variants in INHalpha gene may not be associated to POF disease.

The stage of follicular development, the degree of granulosa cells differentiation and the concentration of local regulators largely determine the characteristics of serum inhibin pattern in females from. birth to adulthood. A representative example of this interplay is the postnatal dimeric inhibin serum profile observed in girls. Another aspect of the complex regulation of ovarian inhibin expression emerges when follicular development and inhibin production are assessed during and after lactational amenorrhoea (LA). To understand the regulatory mechanisms involved, cultured granulosa cells have been used to study the effect of hormones and gonadal factors on inhibin production. The inhibin/activin beta B-subunit gene seems to be a specific target for activin A, TGF-beta, oocyte-derived factor(s) and FSH glycosylation variants bearing complex oligosaccharides.