Advances in clinical and experimental medicine : official organ Wroclaw Medical University · 2015
Brdt Bromodomains Inhibitors and Other Modern Means of Male Contraception.
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Zdrojewicz Zygmunt, Konieczny Radosław, Papier Paulina, Szten Filip
Аннотация
Compared to efficient and secure female contraception, a vasectomy and condoms are the only options for men. The choice of male contraceptive methods is limited, so contraception mainly rests on the shoulders of women. Several concepts are considered: testosterone administration--inhibiting pituitary secretion of lutropin (LH) and follicle stimulating hormone (FSH), progestogen--affecting the secretion of gonadotropin and gonadoliberin (GnRH) antagonists. New potential targets for non-hormonal male contraception were discovered: glyceraldehyde-3-phosphate-dehydrogenase (GAPDHS)--specific to male germ cells and voltage-gated cation channel (CatSper). Both are responsible for sperm motility. Drugs such as thioridazine used in schizophrenia treatment and phenoxybenzamine (antihypertensive activity) exhibit a contraceptive effect. Similar action exhibits an analogue of lonidamine--adjudin and an antagonist of retinoic acid receptors (BMS-189453). Researchers are working on a contraceptive vaccine, whose active ingredient is epididymal protease inhibitor (Eppin). Another promising method acts by blocking Bromodomain testis-specific proteins (Brdt) involved in the process of spermatogenesis. JQ1-the Brdt inhibitor causes reversible infertility without affecting the endocrine signaling pathways. A recent discovery of Juno as the binding partner for Izumo1 identifies these proteins as the cell-surface receptor pair, essential for gamete recognition and this interaction can be inhibited by an anti-Juno monoclonal antibody. Our review shows that the situation of men can change and investigators are close to the optimal solution. In the near future men will be able to choose the best contraceptive suited to their needs.