Biochemical and genetic studies on inhibin as a hormonal candidate in prediction and diagnosis of premature ovarian failure in the Egyptian women

Background: Recent studies have implicated a role for inhibin alpha [INH alpha] gene abnormalities in the etiology of premature ovarian failure [POF].The present study aimed at demonstrating the possibility that -16C>T polymorphism of INH alpha gene may enhance susceptibility to this disease among Egyptian women undergoingt in-vitro fertilization[IVF] technique

Methods: A total of 50 POF Egyptian women at age [31.5 +/- 7.3] and 50 control women at age [29.1 +/- 6.8] were included in this study. Genotyping of INH alpha-16C>T gene was performed by restriction fragment length polymorphism. Levels of inhibin, activin, FSH and LH were also assessed

Results: Serum levels of FSH and LH showed significant increase coupled by decrease in serum inhibin and inhibin/activin ratio, however, levels of activin were within normal values in POF women comparing to control ones. The frequencies of CC, CT and TT genotypes showed no significant changes in POF women compared to control group. Moreover, there were no significant differences in frequency of C and T alleles among the POF women in comparison to controls

Conclusion: Obtained data indicated that -16C>T polymorphism of INH alpha gene can not imply a functional effect on the current decline of serum inhibin and hence the risk of developing POF in the studied Egyptian women. Further studies on POF women are needed to expand the present data

Mesoderm enhancing effect of human seminal plasma inhibin and its synthetic C-terminal nonapeptide fragment in the chick embryo.

Isomers of fibroblast growth factor and members of the transforming growth factor beta family have been identified as potent mesoderm inducing factors, particularly in amphibians. Activins belonging to the latter group are capable of inducing all types of mesoderm. Inhibins, also belonging to the same family of proteins have an exactly opposite biological action than activins in the adult organism. We have examined the effects of human seminal plasma inhibin on the early development of the chick embryo, where also activins appear to be important in mesoderm induction. Contrary to expectations, inhibin brought about stimulation of development of somites and heart, structures of mesodermal origin, and increase in the body length in more than 50% of the treated chick blastoderms. A synthetic fragment of human seminal plasma inhibin, a nonapeptide fragment of C-terminal end, also exhibited similar effects. In some cases the treatments resulted in completely abnormal development while in some increase in the number of somites was associated with abnormality in the anterior region. Our results demonstrate that human seminal plasma inhibin does not act as an inhibitor of mesoderm induction in the chick embryo but in amniotes inhibin-related molecules may have a role as mesoderm enhancers.

Interrelationship between ovine follicular fluid inhibin and serum albumin.

Ovine follicular fluid inhibin (oFF-I) as isolated in this laboratory, proved to be a monomeric protein (M(r).65 kDa). It was found to share very many of the physico-chemical characteristics of ovine serum albumin (oSA)-such as molecular size, iso-electric point, N-terminal aminoacid, finger-print patterns following enzymatic or cyanogen bromide cleavage, as well as binding of estradiol-17 beta and tryptophan. Furthermore, an antiserum containing polyclonal antibodies to oSA showed perfect cross-reaction with oFF-I. Nevertheless, oFF-I is distinct and different from oSA, as would be evident from the data reported here. Of the two proteins, oFF-I alone is capable of suppressing pituitary FSH output in a dose-dependent manner. Secondly, an antiserum containing polyclonal antibodies against Fraction-S2, a partially purified, biologically active fragment (M(r): 30-40 kDa)-derived from oFF-I, cross-reacted with the 65 kDa inhibin, but did not recognize oSA. Finally, the CD-spectra of the two proteins, when examined as a function of pH, show characteristic differences.

On multiple forms of bovine seminal plasma inhibin.

Out of a possible minimum of four, three distinct molecular species of bovine seminal plasma inhibin-differing either in Mr or in pI--have been purified to homogeneity. All three molecules exhibit the same proportion of alpha-helicity and beta-form when examined for their CD-spectra in a non-aqueous solvent medium. The implication of this finding for an induced conformation at the receptor-binding site for these hormonal peptides is briefly discussed.