Isolation of inhibin like peptides from human placenta

Two moieties of inhibin could be obtained by chromatography of partially purified preparations of inhibin from human placenta on Sephadex G-100, G-25 and ion exchange chromatography on diethylaminoethyl Sephadex A-50. The higher molecular weight moiety (14,000) designated as HPI-H appears to be similar to inhibin from human seminal plasma. While the lower molecular weight moiety (1500) designated as HPI-L appears to be similar to that of sheep testicular inhibin. The preparations from both human term placenta and human seminal plasma inhibited the binding of [125I] human follicle stimulating hormone to rat testicular receptors. This effect of inhibins could be neutralized by antisera raised against corresponding polypeptide. Further these antibodies could neutralize endogenous inhibin resulting in 2 to 3 fold increase in serum follicle stimulating harmone levels, which could then be reversed by exogenous administration of the isolated inhibin preparations

Development of antifertility vaccine using sperm specific proteins

Sperm proteins are known to be associated with normal fertilization as auto- or iso-antibodies to these proteins may cause infertility. Therefore, sperm proteins have been considered to be the potential candidate for the development of antifertility vaccine. Some of the sperm proteins proved to be promising antigens for contraceptive vaccine includes lactate dehydrogenase (LDH-C4), protein hyaluronidase (PH-20), and Eppin. Immunization with LDH-C4 reduced fertility in female baboons but not in female cynomolgus macaques. Active immunization with PH-20 resulted in 100 per cent inhibition of fertility in male guinea pigs but it induced autoimmune orchitis. Immunization with Eppin elicited high antibody titres in 78 per cent of immunized monkeys and induced infertility but the immunopathological effect of immunization was not examined. Human sperm antigen (80kDa HSA) is a sperm specific, highly immunogenic and conserved sperm protein. Active immunization with 80kDa HSA induced immunological infertility in male and female rats. Partial N-terminal amino acid sequence of 80kDa HSA (Peptide NT) and its peptides (Peptides 1, 2, 3 and 4) obtained by enzymatic digestion did not show homology with any of the known proteins in gene bank. Peptides NT, 1, 2 and 4 were found to mimic immunobiological activity of native protein. Passive administration of antibodies to peptides NT, 1, 2 and 4 induced infertility in male and female rats and peptide 1 was found to be most effective in suppressing fertility. Active immunization with keyhole limpet haemocynin (KLH) conjugated synthetic peptide 1 impaired fertility in all the male rabbits and six of the seven male marmosets. The fertility was restored following decline in antibody titre. All these findings on 80kDA HAS suggest that the synthetic Peptide-1 of 80kDa HSA is the promising candidate for development of male contraceptive vaccine

Agglutination of human spermatozoa with antibodies to inhibin

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Endocrine control of inhibin biosynthesis by human placenta

In vitro synthesis of inhibin-like activity was localized in the fetal part of the human placenta. Of the various hormones, hCG stimulated inhibin synthesis while progesterone, estradiol, LHRH and prostaglandin inhibited the synthesis. Prolactin did not significantly alter the inhibin synthesis

Antibodies to human seminal plasma inhibin cause sperm agglutination and impairment of cervical mucus penetration and sperm-egg attachment

Inhibin isolated from human seminal plasma which has 94 amino acids has been shown to be structurally similar to a sperm coating antigen of prostatic origin. Specific antibodies generated against this peptide caused agglutination of human sperm. Using FITC-labeled antibody, antigen was localized on the post-acrosomal head region of sperm. Antiserum to inhibin could also impair the penetration of human spermatozoa into cervical mucus. After 10 and 30 minutes, the depth and density of penetration as well as the motility of the sperm were inhibited. The treatment of sperm with antiserum to inhibin caused an inhibition of sperm attachment to the egg as well as inhibition of penetration

Evidence for mutually antagonistic actions of thyroid releasing hormone and inhibin at pituitary-gonadal-prostate-spermatozoal axis

In-vivo as well as in-vitro studies carried out demonstrate for the first time the interaction between thyroid releasing hormone (TRH) and inhibin at the pituitary, testes, prostate and spermatozoa levels. At the pituitary level both peptides act as antagonists to each other and modify the release of pituitary hormones. Further, these peptides act at the prostatic level wherein they modulate ornithine decarboxylase activity as well as 5 α-reductase activity. At the testicular level TRH blocks inhibin biosynthesis whereas in semen, it significantly reduces the binding of spermatozoa to specific antibodies directed against inhibin. In conclusion, although TRH and inhibin are widely different in their molecular size and chemical structure, these peptides seems to act antagonistically at multiple sites

Antifertility effects of human sperm antigen in female rats

The sperm antigens responsible for inducing infertility were identified by Western blot technique using sera from an infertile woman with circulating antisperm antibodies. The 80 Kda was prepared from human sperm by extraction with 0.05% sodium deoxycholate in 0.01 M Tris-HCl buffer, pH 8.4 and fractionation with ammonium sulphate. The supernatant after 40% saturation ammonium sulphate extraction was separated by gel-permeation chromatography, using HPLC (Protein PAK 125 column) and FPLC (superose 12 column) systems. The homogeneity of the protein was established by SDS-PAGE and its molecular size was estimated to be 80 Kda and its isoelectric point was 4.5. The purified protein upon active immunization in female rats caused infertility in 100 percent animals. The data suggest that 80 Kda human sperm antigen has the potential for use as a contraceptive vaccine

Modulation of FSH action by inhibin

Both testicular and ovarian inhibin preparations caused a dose-related inhibition of binding of <SUP>125</SUP>I-hFSH to rat testicular receptors. Testicular inhibin also suppressed the FSH-induced production of cAMP by rat testis in vitro. These data demonstrate a direct action of inhibin at the testicular level by interfering with FSH action