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      γ-Aminobutyric acid suppresses enhancement of hamster sperm hyperactivation by 5-hydroxytryptamine

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          Abstract

          Sperm hyperactivation is regulated by hormones present in the oviduct. In hamsters, 5-hydroxytryptamine (5HT) enhances hyperactivation associated with the 5HT 2 receptor and 5HT 4 receptor, while 17β-estradiol (E 2) and γ-aminobutyric acid (GABA) suppress the association of the estrogen receptor and GABA A receptor, respectively. In the present study, we examined the regulatory interactions among 5HT, GABA, and E 2 in the regulation of hamster sperm hyperactivation. When sperm were exposed to E 2 prior to 5HT exposure, E 2 did not affect 5HT-enhanced hyperactivation. In contrast, GABA partially suppressed 5HT-enhanced hyperactivation when sperm were exposed to GABA prior to 5HT. GABA suppressed 5HT-enhanced hyperactivation associated with the 5HT 2 receptor although it did not suppress 5HT-enhanced hyperactivation associated with the 5HT 4 receptor. These results demonstrate that hamster sperm hyperactivation is regulated by an interaction between the 5HT 2 receptor-mediated action of 5HT and GABA.

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          Most cited references28

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          Nongenomic activation of spermatozoa by steroid hormones: facts and fictions.

          The rapid effects of steroids on spermatozoa have been demonstrated for the first time two decades ago. Progesterone (P), which is present throughout the female genital tract with peaks of levels in the cumulus matrix surrounding the oocyte, stimulates several sperm functions, including hyperactivation and acrosome reaction. These effects are mediated by an extranuclear pathway, as P stimulates an influx of calcium, the tyrosine phosphorylation of sperm proteins and other signalling cascades in a rapid manner. Whether these effects are receptor mediated and which receptors mediate these effects are still a matter of discussion despite all the efforts of the scientific community aimed at identifying them during the last 20 years. Although responsiveness to P is related to sperm fertilizing ability, the physiological role of P during the process of fertilization is discussed, and recent evidence points for a role of the steroid as a chemotactic agent for sperm. A similar situation applies for estrogens (E), which have been shown to induce direct effects on sperm by an extranuclear pathway. In particular, E appear to decrease acrosome reaction in response to P, exerting a role in ensuring an appropriate timing for sperm exocytosis during the process of fertilization.
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            GABA-Activated ligand gated ion channels: medicinal chemistry and molecular biology.

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              The in vitro effects of melatonin on human sperm function and its scavenging activities on NO and ROS.

              Various systems of antioxidants exist endogenously in the body to help protect it against free radical damage by scavenging excessive ROS and RNS. Melatonin, a hormone secreted by the pineal gland, and responsible for controlling the circadian rhythm, is one such endogenous antioxidant. Melatonin has been reported to be present in human seminal fluid, but its antioxidant activities in semen are rather contradictory. This study aimed at establishing the effects of melatonin treatment on human spermatozoa. Spermatozoa were incubated with 2 mm melatonin (120 min, 37 degrees C, 5% CO(2)) after which motility parameters were measured by computer aided motility analysis, while cell viability (PI), intracellular NO (DAF-2/DA) and ROS (DCFH-DA) were assessed using flow cytometry. In vitro melatonin treated samples (n = 12) showed a significantly higher percentage of motile, progressive motile and rapid cells, while simultaneously reducing the number of nonviable spermatozoa when compared with the control. Endogenous NO was significantly decreased, but no effect was observed on ROS levels. From these results, it can be concluded that melatonin was able to directly or indirectly scavenge NO, as indicated by the reduction in 4,5-diaminofluorescein-2/diacetate fluorescence. Future studies will indicate whether melatonin treatment during sperm preparation techniques could protect spermatozoa from excessive NO production.
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                Author and article information

                Journal
                J Reprod Dev
                J. Reprod. Dev
                JRD
                The Journal of Reproduction and Development
                The Society for Reproduction and Development
                0916-8818
                1348-4400
                24 October 2016
                February 2017
                : 63
                : 1
                : 67-74
                Affiliations
                [1) ]Department of Physiology, School of Medicine, Dokkyo Medical University, Tochigi 321-0293, Japan
                Author notes
                Correspondence: M Fujinoki (e-mail: fujinoki@ 123456dokkyomed.ac.jp )
                Article
                2016-091
                10.1262/jrd.2016-091
                5320432
                27773888
                27d1ae13-d7d9-4583-8d52-97b4e52322c9
                ©2017 Society for Reproduction and Development

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (by-nc-nd) License. (CC-BY-NC-ND 4.0: http://creativecommons.org/licenses/by-nc-nd/4.0/ )

                History
                : 07 June 2016
                : 05 October 2016
                Categories
                Original Article

                γ-aminobutyric acid,capacitation,5-hydroxytryptamine,hyperactivation,sperm

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