Signal transduction by arachidonic acid metabolites in trophic hormone-induced steroidogenesis and molecular mechanism regulating steroid hormone biosynthesis in male aging
Aging process of males is associated with the decrease in an important steroid hormone, testosterone in blood. The decrease in blood testosterone concentration results in declines in many physiological functions. But the mechanism for the age-related decrease in testosterone is not clear. We have found that cyclooxygenase-2 (COX2) expression increased in testicular Leydig cells of aging male rats. The increase in COX2 depressed the gene expression of steroidogenic acute regulatory (StAR) protein that regulates the rate-limiting step of steroidogenesis. Consequently, the aged-related increase in COX2 resulted in the decline in testosterone biosynthesis. We have also successfully reversed the declines in blood testosterone and StAR protein by feeding aged male rats with a COX2 inhibitor. Our findings suggest a possibility to delay or overcome the age-related decrease in testosterone by intervention in the mechanism. Currently, we are studying potential applications of the findings, through molecular, pharmaceutical and nutritional approaches, to improve the health of aging males and to explore the possibility of delaying their aging process.