Oxidative stress lowers testosterone production

Oxidative stress impairs steroids production (testosterone, progesterone):

knockdown of Sirt1 or Nrf2, increased ROS levels and decreased progesterone production occurred. In rat Leydig cells, inhibition of Sirt1 by culturing the cells with NAM resulted in increased ROS and reduced testosterone production, and subsequent removal of NAM from the culture medium resulted in increased testosterone production.

Activation of rat Leydig cells Sirt1 with honokiol or of Nrf2 with sulforaphane resulted in the maintenance of testosterone production despite the exposure of the cells to oxidizing agent.

These results, taken together, suggest that Sirt1 and Nrf2 are involved in maintaining the Leydig cell oxidant/antioxidant environment, and thus in maintaining steroid production. (R1)

(the study was done on rats)

Other interesting insights from this paper

• Taking Niacinamide (NAM) can cause increased ROS and decrease of testosterone as a result. Think about PRPP availablity and B1 status to maintain PRPP.
• Use of KEAP1 inhibitor (Sulforaphane) rescued testosterone production.
• Cholesterol translocation is the rate-determining step in steroid production
• Reduced serum levels of testosterone (hypogonadism) can occur in both young and aging men
• Reduced serum testosterone results from reduced Leydig cell testosterone production
• Testosterone is produced by the testicular Leydig cells. Its production is regulated by luteinizing hormone (LH)
• serum LH levels typically do not change with age, but rather there is reduced responsiveness of the aging Leydig cells to LH that results in reduced testosterone production
• defiicts contributing to the loss of sensitivity: reductions in cAMP production, proteins involved in cholesterol transfer and translocation from the cytosol into the mitochondria, and steroidogenic enzymes of the mitochondria and smooth endoplasmic reticulum.