Regulation of the sperm calcium channel CatSper by endogenous steroids and plant triterpenoids.
نویسندگان
چکیده
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.
منابع مشابه
Action of steroids and plant triterpenoids on CatSper Ca2+ channels in human sperm.
The sperm-specific Ca channel CatSper (cation channel of sperm) controls the intracellular Ca concentration and, thereby, the swimming behavior of sperm. Human CatSper is activated by progesterone (1, 2), an oviductal hormone, which stimulates Ca influx and motility responses. By patch-clamp recording from human sperm, Mannowetz et al. (3) studied the action of the steroids pregnenolone sulfate...
متن کاملReply to Brenker et al.: The plant triterpenoid pristimerin inhibits calcium influx into human spermatozoa via CatSper.
In the letter by Brenker et al. (1), the authors assessed actions of various steroids toward the human calcium channel of sperm (CatSper). The experiments, carried out with calcium imaging, are minimally supplemented by electrophysiology. The authors show that all tested steroids activate CatSper with different efficiencies. However, the plant triterpenoids pristimerin and lupeol fail to interf...
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Background: Low levels of reactive oxygen species (ROS) and calcium are necessary for sperm function. NADPH oxidase 5 (NOX5) is a membrane enzyme which produces ROS. This enzyme is dependent on calcium for its activity. We investigated the importance of NOX5 and an important calcium channel (CatSper) on sperm function.Methods: This laboratory in-vitro study was done in Shiraz, Iran, 2016. Norma...
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Background: Normal sperm function depends on appropriate intracellular calcium (Cai2+) and reactive oxygen species (ROS) levels. Calcium activates NADPH oxidase-5 (NOX5) that leads to ROS generation. The calcium channel of sperm (CatSper) is activated by progesterone and intracellular alkalization. Herein, the interactive role of CatSper, Hv1 channels, and NOX5 enzyme on Cai2+ and ROS generatio...
متن کاملThe Catsper channel and its roles in male fertility: a systematic review
The Catsper channel is a sperm-specific, Ca2+-permeable, pH-dependent, and low voltage-dependent channel that is essential for the hyperactivity of sperm flagellum, chemotaxis towards the egg, capacitation and acrosome reaction. All of these physiological events require calcium entry into sperm cells. Remarkably, Catsper genes are exclusively expressed in the testis during spermatogenesis, and ...
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ورودعنوان ژورنال:
- The Journal of urology
دوره 198 5 شماره
صفحات -
تاریخ انتشار 2017