ReferenceID 3439

Regulation of the sperm calcium channel CatSper by endogenous steroids and plant triterpenoids

Proc Natl Acad Sci U S A

The calcium channel of sperm (CatSper) is essential for sperm hyperactivated motility and fertility. The steroid hormone progesterone activates CatSper of human sperm via binding to the serine hydrolase ABHD2. However, s

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Reference Id
3439
Evidence Id
20029
Core Evidence Id
20029
Source Reference Id
185
Herb2 Reference Id
HBREF000372
Subject Paper Key
HBIN033751_28507119
Pubmed Id
28507119
Doi
10.1073/pnas.1700367114
Paper Title
Regulation of the sperm calcium channel CatSper by endogenous steroids and plant triterpenoids
Paper Abstract
The calcium channel of sperm (CatSper) is essential for sperm hyperactivated motility and fertility. The steroid hormone progesterone activates CatSper of human sperm via binding to the serine hydrolase ABHD2. However, steroid specificity of ABHD2 has not been evaluated. Here, we explored whether steroid hormones to which human spermatozoa are exposed in the male and female genital tract influence CatSper activation via modulation of ABHD2. The results show that testosterone, estrogen, and hydrocortisone did not alter basal CatSper currents, whereas the neurosteroid pregnenolone sulfate exerted similar effects as progesterone, likely binding to the same site. However, physiological concentrations of testosterone and hydrocortisone inhibited CatSper activation by progesterone. Additionally, testosterone antagonized the effect of pregnenolone sulfate. We have also explored whether steroid-like molecules, such as the plant triterpenoids pristimerin and lupeol, affect sperm fertility. Interestingly, both compounds competed with progesterone and pregnenolone sulfate and significantly reduced CatSper activation by either steroid. Furthermore, pristimerin and lupeol considerably diminished hyperactivation of capacitated spermatozoa. These results indicate that (i) pregnenolone sulfate together with progesterone are the main steroids that activate CatSper and (ii) pristimerin and lupeol can act as contraceptive compounds by averting sperm hyperactivation, thus preventing fertilization.
Journal
Proc Natl Acad Sci U S A
Publish Year
2017
Experiment Subject
Experiment Type
Cell Experiment
Phenotype Related
Sperm Hyperactivated Motility
Paper Title Cn
Paper Title En
Regulation of the sperm calcium channel CatSper by endogenous steroids and plant triterpenoids
Bilingual Status
semi_complete