Abstract
Androgens, especially testosterone produced in Leydig cells, play an essential role in development of the male reproductive phenotype and fertility. However, testicular oxidative stress may cause a decline in testosterone production. Many antioxidants have been used as reactive oxygen species (ROS) scavengers to eliminate oxidative stress to protect steroidogenesis. Astaxanthin (AST), a natural extract from algae and plants ubiquitous in the marine environment, has been shown to have antioxidant activity in many previous studies. In this study, we treated primary mouse Leydig cells or MA-10 cells with hydrogen peroxide (H2O2) to cause oxidative stress. Testosterone and progesterone production was suppressed and the expression of the mature (30 kDa) form of StAR protein was down-regulated in MA-10 cells by H2O2 and cAMP co-treatment. However, progesterone production and expression of mature StAR protein were restored in MA-10 cells by a one-hour pretreatment with AST. AST also reduced ROS levels in cells so that they were lower than the levels in untreated controls. These results provide additional evidence of the potential health benefits of AST as a potential food additive to ease oxidative stress.
Highlights
Androgen plays an essential role in the development of the male reproductive phenotype and fertility.More than 95% of circulating androgens are derived from the testis while the remainder is primarily produced by the adrenals
To clarify the potential effects of AST, after pre-treatment with 10 μg/mL AST for 1 h, MA-10 cells were treated with 100 μM 8-Br-cAMP, 1 μg/mL 22R-OHC, or 1 μg/mL pregnenolone to stimulate progesterone production and co-treated with 100 μM H2O2 for an additional 3 h to establish an oxidative stress while the cells were still being exposed to AST they were co-treated with 100 μM H2O2 for an additional 3 h to establish an oxidative stress
We found that even progesterone production supported by exogenous steroidogenic substrates including 22R-OHC and pregnenolone was suppressed under the oxidative
Summary
Androgen plays an essential role in the development of the male reproductive phenotype and fertility.More than 95% of circulating androgens are derived from the testis while the remainder is primarily produced by the adrenals. Androgen plays an essential role in the development of the male reproductive phenotype and fertility. Through its G protein coupled receptor, LH activates adenylyl cyclase by stimulating G protein and inducing production of the intracellular second messenger cAMP, followed by activation of the PKA pathway and promotion of the expression of key steroidogenic genes. These genes include steroidogenic acute regulatory protein (StAR), which transports cholesterol into mitochondria, and Cyp11a1, which cleaves the side chain of cholesterol and catalyzes its conversion into pregnenolone (P5). Disturbance of testosterone synthesis or its functions may cause incomplete masculinization before puberty and many reproductive disorders, including poor sperm production, poor sperm quality, azoospermia, cryptorchidism, hypospadias, and even testicular cancer [2]
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