男性避妊薬現る？

A pharmacologic approach to male contraception remains a longstanding challenge in medicine. Toward this objective, we explored the spermatogenic effects of a selective small-molecule inhibitor (JQ1) of the bromodomain and extraterminal (BET) subfamily of epigenetic reader proteins. Here, we report potent inhibition of the testis-specific member BRDT, which is essential for chromatin remodeling during spermatogenesis. Biochemical and crystallographic studies confirm that occupancy of the BRDT acetyl-lysine binding pocket by JQ1 prevents recognition of acetylated histone H4. Treatment of mice with JQ1 reduced seminiferous tubule area, testis size, and spermatozoa number and motility without affecting hormone levels. Although JQ1-treated males mate normally, inhibitory effects of JQ1 evident at the spermatocyte and round spermatid stages cause a complete and reversible contraceptive effect. These data establish a new contraceptive that can cross the blood:testis boundary and inhibit bromodomain activity during spermatogenesis, providing a lead compound targeting the male germ cell for contraception.
Small-Molecule Inhibition of BRDT for Male Contraception
Cell, Volume 150, Issue 4, 673-684, 17 August 2012 Martin M Matzuk
ヒストンH4のアセチル化リジンを認識して結合し染色体のリモデリングをするタンパクBRDTを抑制すると精子ができなくなる。男性ホルモンは減らないのでsexは変わりなくするが睾丸が小さくなる。BRDT抑制剤のJQ1は小分子なので副作用がなければ飲める薬になるだろう。ということは逆にいうと同様の環境物質によって不妊になっている人もいるかもしれないわけだ。