The effect of macrophage conditioned media on Leydig cell function

Primary gonadal failure frequently occurs in male patients with serious illness. This has suggested that activation of the immune system may affect the endocrine function of the testis. Most previous studies have evaluated the effects of individual cytokines on testosterone (T) production but with conflicting results. The present study was performed to compare the effects on Leydig cell function of a mixture of cytokines found in macrophage conditioned media (MCM), with that of individual recombinant cytokines. The MCM was found to contain an acid stable, heat labile, 16.5 kD factor(s) which significantly decreased the production of testosterone (T), dihydrotestosterone (dHT), adenosine 3':5'-cyclic monophosphate (cAMP), and guanosine 3':5'-cyclic monophosphate (cGMP). The MCM had no effect on the specific binding of human chorionic gonadotropin (hCG) but decreased the activity of 3-beta-hydroxysteroid dehydrogenase (3-beta-HSD) (a regulated Leydig cell enzyme). Neither tumor necrosis factor alpha (TNF alpha) interleukin 1 alpha (IL1 alpha), interleukin 1 beta (IL1 beta), interleukin 2 (IL2), interleukin 6 (IL6), or human interferon alpha,beta (IFN alpha,beta) had a similar effect. These results show that the cytokines or other factor(s) contained in MCM are potent regulators of T production, which could be important in understanding the low serum T levels associated with serious illness.