α/β hydrolase domain–containing protein 2 (ABHD2) is a serine hydrolase enzyme that is expressed in spermatozoa, as well as in other cell types across the body.
ABHD2 plays an essential role in fertility. Upon being bound by Progesterone, the enzyme cleaves 2-arachidonoylglycerol (2-AG), which is an endocannabinoid inhibitor of CatSper. In Mannowetz et al., 2017, we showed that pregnenolone sulfate, not endogenous to the female reproductive tract, also activates CatSper via ABHD2. Other steroids – including testosterone, estradiol, and hydrocortisone – have in fact been shown by our lab to interfere with progesterone’s activation of the CatSper channel in human sperm. This discovery suggests that non-progesterone steroids or the structurally similar triterpenoids could act as contraceptives through interference with progesterone activation of CatSper.
In Miller et al., 2018, it was shown that ABHD2 follows a quadrilateral distribution along the principal piece, similar to that of CatSper.