ANDROGEN-BINDING SITES IN PERIPHERAL HUMAN MONONUCLEAR LEUKOCYTES OF HEALTHY-MALES AND FEMALES

Androgen binding sites have been identified in circulating human monon uclear leukocytes of healthy donors of both sexes. Cells were separate d from blood samples on a Ficoll gradient and incubated with different concentrations of [H-3]testosterone in the presence or absence of a 4 00-fold excess of unlabelled testosterone. Binding data were derived f rom Scatchard analysis. The binding sites fulfil the required criteria for specific steroid binding sites however differ somewhat from the c lassic androgen receptors from genital skin fibroblast: in fertile adu lt males (n = 20) the binding sites showed (1) a high affinity for tes tosterone (1.32 +/- 0.49 nM; mean +/- SD), (2) a saturable capacity (1 84 +/- 52 binding sites per cell; mean +/- SD), and (3) a characterist ic competitive binding profile for other steroid hormones (relative bi nding affinities: testosterone=dihydrotestosterone > 17 beta-estradiol > progesterone, whereas aldosterone, 17-hydroxy-progesterone and cort isol did not compete appreciably). Furthermore the number of binding s ites determined using [H-3]dihydrotestosterone, [H-3]RU-1881, or [H-3] testosterone were comparable. This raises the possibility that androge n receptors in peripheral mononuclear leukocytes differ from those in genital skin fibroblasts. There was no apparent correlation between se rum testosterone concentrations and androgen binding sites. In fertile women remarkable changes in androgen binding sites were seen in the c ourse of the menstrual cycle, with a significant increase in the immed iate preovulatory period. The presence of androgen receptors in periph eral mononuclear leukocytes provides for the first time the experiment al basis for an hypothesis of direct, receptor-mediated effects of and rogens on mature immunocompetent cells. The immunological implications of these results are discussed.