The cross talk of adrenal and Leydig cell steroids in Leydig cells

•Glucocorticoid binds to GR to inhibit testosterone production in Leydig cells.•Glucocorticoid binds to MR to stimulate testosterone production in Leydig cells.•11β-Hydroxysteroid dehydrogenases control glucocorticoid levels in Leydig cells.•11β-Hydroxysteroid dehydrogenase 1 direction is coupled by several steroidogenic enzymes. Glucocorticoid is secreted by adrenal cortex, which binds to intracellular glucocorticoid and mineralocorticoid receptors to regulate steroidogenesis-related gene expression and testosterone production in Leydig cells. Glucocorticoid receptor activity shows inhibitory action on Leydig cell steroidogenesis, while mineralocorticoid receptor activity shows the stimulatory action. Leydig cells contain two important glucocorticoid-metabolizing enzymes, 11β-hydroxysteroid dehydrogenase type 1 and type 2, regulating the intracellular levels of glucocorticoids by a pre-receptor mechanism. 11β-Hydroxysteroid dehydrogenase type 1 is a bidirectional enzyme, and its direction is regulated by intracellular NADP+/NADPH redox potential. Leydig cells contain many steroidogenic enzymes, possibly regulating NADP+/NADPH redox potential by coupling with 11β-hydroxysteroid dehydrogenase type 1. Here, we review the 11β-hydroxysteroid dehydrogenase regulation and possible consequences in Leydig cell biology and pathology.