Regulation of the sperm calcium channel CatSper by endogenous steroids and plant triterpenoids
2017; National Academy of Sciences; Volume: 114; Issue: 22 Linguagem: Inglês
10.1073/pnas.1700367114
ISSN1091-6490
AutoresNadja Mannowetz, Melissa Miller, Polina V. Lishko,
Tópico(s)Natural Compounds in Disease Treatment
ResumoSignificance The calcium channel of sperm—CatSper—is vital for male fertility. CatSper is activated by the hormone progesterone, but its pharmacological profile is not well studied. By exploring steroid selectivity of CatSper activation, we found one additional agonist—pregnenolone sulfate—and the two plant-derived inhibitors pristimerin and lupeol. By averting sperm hyperactivation, both inhibitors can prevent fertilization, thus acting as contraceptive agents. Additionally, by exploring CatSper regulation by endogenous steroids, we explain why CatSper is silent within the male reproductive tract and is only activated in close proximity to the egg. Interestingly, both testosterone and hydrocortisone antagonize the action of progesterone at physiological concentrations, which may explain why elevated levels of these steroids in the female organism affect fertility.
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