Stress-induced glucocorticoids alter the Leydig cells' timing and steroidogenesis-related systems.

The study aimed to analyze the time-dependent consequences of stress on gene expression responsible for diurnal endocrine Leydig cell function connecting them to the glucocorticoid-signaling. In the first 24h after the stress event, a daily variation of blood corticosterone increased, and testosterone decreased; the testosterone/corticosterone were lowest at the end of the stress session overlapping with inhibition of Leydig cells' steroidogenesis-related genes (Nr3c1/GR, Hsd3b1/2, Star, Cyp17a1) and changed circadian activity of the clock genes (the increased Bmal1/BMAL1 and Per1/2/PER1 and decreased Cry1 and Rev-erba). The glucocorticoid-treated rats showed a similar response. The principal-component-analysis (PCA) displayed an absence of significant differences between treatments especially on Per1 and Rev-erba, the findings confirmed by the in vivo blockade of the testicular glucocorticoid receptor (GR) during stress and ex vivo treatment of the Leydig cells with hydrocortisone and GR-blocker. In summary, stressful stimuli can entrain the clock in the Leydig cells through glucocorticoid-mediated communication.