Annexin 1 (lipocortin 1) mimics inhibitory effects of glucocorticoids on testosterone secretion and enhances effects of interleukin-1beta

Annexin 1 is an important mediator of glucocorticoid action in the hypothalamo-pituitary axis; however, little is known of its role in mediating glucocorticoid actions in the peripheral endocrine organs. Accordingly, we have carried out a preliminary study to investigate the effects of annexin 1 in vitro on the testicular secretion of testosterone, a process inhibited by both glucocorticoids and interleukin-1beta (IL-1beta). Luteinizing hormone (LH) and forskolin stimulated the release of testosterone from dispersed murine testicular cells in vitro. Their effects were reduced in cells from mice pretreated with dexamethasone (DEX). Similarly, preincubation of testicular cells from untreated mice with DEX, corticosterone, or 11-dehydrocorticosterone reduced LH-stimulated testosterone release, as did the 11beta-hydroxysteroid dehydrogenase inhibitors, glycyrrhetinic acid and carbenoxolone. The inhibitory actions of the steroids were mimicked by annexin 1(1-188) (ANXA1(1-188)) (a stable annexin 1 analog). IL-1beta produced a marked decrease in the response to LH, which was blocked by indomethacin, a nonselective cyclooxygenase inhibitor and an additive effect with DEX and ANXA1(1-188). These results confirm reports that glucocorticoids and IL-1beta inhibit LH-stimulated testosterone release from mouse testicular cells. They also show, for the first time, that the effects of the steroids are mimicked by annexin 1 and that, in contrast to their mutually antagonistic effects in the neuroendocrine system, IL-1beta and annexin 1 exert additive actions in the testis.