Abstract
Leydig cells in the testis produce testosterone under the control of luteinizing hormone (LH) secreted by the anterior pituitary. LH binds to the Gs protein-coupled LH receptor in Leydig cells and increases intracellular levels of cyclic AMP, which stimulates testosterone production by regulating the expression of steroidogenic enzymes and others. Testosterone is critical for male physiology, including gonadal function, muscle mass, lipids, bone formation, and erythropoiesis. Butyrate, a short-chain fatty acid (SCFA) produced by butyrate-producing bacteria in the gut, is associated with inflammasome and immune function. In this study, we investigated the role of butyrate in testosterone production in testicular Leydig cells.
In the mouse Leydig tumor cell line (MLTC1), treatment with dibutyryl (db)-cAMP increased testosterone levels in the culture medium. Treatment with butyrate suppressed the db-cAMP-stimulated testosterone production. Notably, butyrate increased the mRNA expression of the steroidogenesis repressor Nr0b1 and decreased that of the steroidogenesis enzymesCyp11a1 and Hsd3b. In addition, treatment with butyrate increased histone H3 acetylation. Taken together, our results suggest that butyrate may decrease testosterone production via modulation of histone acetylation and steroidogenic factors expression in Leydig cells and affect the development and maintenance of male physiological function.
