Cysteine Sulfoxides Enhance Steroid Hormone Production via Activation of the Protein Kinase A Pathway in Testis-Derived I-10 Tumor Cells

Nakayama, Yuichiro; Ho, Hsin Jung; Yamagishi, Miki; Ikemoto, Hiroyuki; Komai, Michio; Shirakawa, Hitoshi

doi:10.3390/molecules25204694

Cited by 10 publications

(7 citation statements)

References 21 publications

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“…Two pharmacokinetic studies have demonstrated that SAC can metabolize to its N-acetylated form and to a lesser extent its sulfoxide form in rats [ 26 , 43 ]. Although the N-acetylated form of SAC and S -allyl cysteine sulfoxide (alliin) have not been reported to have a steroidogenic effect in vivo or in vitro, structurally similar compounds like propenyl-1-cysteine sulfoxide (isoalliin) and cycloalliin from onion extract have been reported to have a steroidogenic effect in I-10 cells [ 13 ]. Moreover, onion juice, which is rich in cysteine sulfoxides, showed a steroidogenic effect in animal-based experiments [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

“…However, its applicability has raised some controversy, as a few cases of cardiovascular events have been reported, followed by TRT [ 8 , 9 ], warranting the search for alternative resources, such as nutritional supplements or natural compounds in diets that have the potential to boost testosterone levels. In this direction, several natural compounds that have the potential to enhance testosterone production either in vitro or in vivo have been explored [ 10 , 11 , 12 , 13 , 14 ]. For instance, vitamin K2 homolog menaquinone-4, geranylgeraniol, and cysteine sulfoxide have been shown to enhance testosterone levels via PKA activation [ 11 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

“…In this direction, several natural compounds that have the potential to enhance testosterone production either in vitro or in vivo have been explored [ 10 , 11 , 12 , 13 , 14 ]. For instance, vitamin K2 homolog menaquinone-4, geranylgeraniol, and cysteine sulfoxide have been shown to enhance testosterone levels via PKA activation [ 11 , 12 , 13 ]. Moreover, numerous flavonoids and isoflavonoid molecules have also been reported to have steroidogenic effects on Leydig cell lines or animal-based models [ 10 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

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S-allyl Cysteine Enhances Testosterone Production in Mice and Mouse Testis-Derived I-10 Cells

et al. 2021

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Hypogonadism, associated with low levels of testosterone synthesis, has been implicated in several diseases. Recently, the quest for natural alternatives to prevent and treat hypogonadism has gained increasing research interest. To this end, the present study explored the effect of S-allyl cysteine (SAC), a characteristic organosulfur compound in aged-garlic extract, on testosterone production. SAC was administered at 50 mg/kg body weight intraperitoneally into 7-week-old BALB/c male mice in a single-dose experiment. Plasma levels of testosterone and luteinizing hormone (LH) and testis levels of proteins involved in steroidogenesis were measured by enzymatic immunoassay and Western blot, respectively. In addition, mouse testis-derived I-10 cells were also used to investigate the effect of SAC on steroidogenesis. In the animal experiment, SAC significantly elevated testosterone levels in both the plasma and the testis without changing the LH level in plasma and increased phosphorylated protein kinase A (p-PKA) levels. Similar results were also observed in I-10 cells. The findings demonstrating the increasing effect of SAC on p-PKA and mRNA levels of Cyp11a suggest that SAC increases the testosterone level by activating the PKA pathway and could be a potential target for hypogonadism therapeutics.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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S-allyl Cysteine Enhances Testosterone Production in Mice and Mouse Testis-Derived I-10 Cells

et al. 2021

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“…Testosterone, a steroid hormone, plays a key role in the development of male sexual characteristics, and its reduction may cause infertility (184). It has been reported that onion extractcontained cysteine sulfoxides could stimulate the production of the testosterone precursor, progesterone, by activating the protein kinase A signaling pathway in a testis-derived cell line (I-10) (117). Bacterial infection is one of the main factors that cause infertility in men.…”

Section: Reproductive System Protectionmentioning

confidence: 99%

Recent Advances in Bioactive Compounds, Health Functions, and Safety Concerns of Onion (Allium cepa L.)

et al. 2021

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Onion (Allium cepa L.) is a common vegetable, widely consumed all over the world. Onion contains diverse phytochemicals, including organosulfur compounds, phenolic compounds, polysaccharides, and saponins. The phenolic and sulfur-containing compounds, including onionin A, cysteine sulfoxides, quercetin, and quercetin glucosides, are the major bioactive constituents of onion. Accumulated studies have revealed that onion and its bioactive compounds possess various health functions, such as antioxidant, antimicrobial, anti-inflammatory, anti-obesity, anti-diabetic, anticancer, cardiovascular protective, neuroprotective, hepatorenal protective, respiratory protective, digestive system protective, reproductive protective, and immunomodulatory properties. Herein, the main bioactive compounds in onion are summarized, followed by intensively discussing its major health functions as well as relevant molecular mechanisms. Moreover, the potential safety concerns about onion contamination and the ways to mitigate these issues are also discussed. We hope that this paper can attract broader attention to onion and its bioactive compounds, which are promising ingredients in the development of functional foods and nutraceuticals for preventing and managing certain chronic diseases.

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“…Male hormone replacement has been used to alleviate LOH symptoms but is reported to be associated with several side effects, warranting the need to develop alternative therapies. Vitamins and other dietary ingredients have attracted attention as safe candidates, and some have been reported to increase testosterone production [6][7][8][9][10][11][12][13]. Biotin is a water-soluble vitamin that functions as a cofactor for carboxylases related to the metabolism of carbohydrates, lipids, and amino acids, from microorganisms to higher organisms [14].…”

Section: Introductionmentioning

confidence: 99%

Biotin Enhances Testosterone Production in Mice and Their Testis-Derived Cells

Shiozawa

Maeda

et al. 2022

Nutrients

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Late-onset hypogonadism, a male age-related syndrome characterized by a decline in testosterone production in the testes, is commonly treated with testosterone replacement therapy, which has adverse side effects. Therefore, an alternative treatment is highly sought. Supplementation of a high dosage of biotin, a water-soluble vitamin that functions as a coenzyme for carboxylases involved in carbohydrate, lipid, and amino acid metabolism, has been shown to influence testis functions. However, the involvement of biotin in testis steroidogenesis has not been well clarified. In this study, we examined the effect of biotin on testosterone levels in mice and testis-derived cells. In mice, intraperitoneal treatment with biotin (1.5 mg/kg body weight) enhanced testosterone levels in the serum and testes, without elevating serum levels of pituitary luteinizing hormone. To investigate the mechanism in which biotin increased the testosterone level, mice testis-derived I-10 cells were used. The cells treated with biotin increased testosterone production in a dose- and time-dependent manner. Biotin treatment elevated intracellular cyclic adenosine monophosphate levels via adenylate cyclase activation, followed by the activation of protein kinase A and testosterone production. These results suggest that biotin may have the potential to improve age-related male syndromes associated with declining testosterone production.

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Cysteine Sulfoxides Enhance Steroid Hormone Production via Activation of the Protein Kinase A Pathway in Testis-Derived I-10 Tumor Cells

Cited by 10 publications

References 21 publications

S-allyl Cysteine Enhances Testosterone Production in Mice and Mouse Testis-Derived I-10 Cells

S-allyl Cysteine Enhances Testosterone Production in Mice and Mouse Testis-Derived I-10 Cells

Recent Advances in Bioactive Compounds, Health Functions, and Safety Concerns of Onion (Allium cepa L.)

Biotin Enhances Testosterone Production in Mice and Their Testis-Derived Cells

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