LYMPHOCYTE SUBSET DISTRIBUTION AND NATURAL-KILLER-CELL ACTIVITY IN MEN WITH IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM

Sex-related differences in immune responsiveness are mediated at least in part by sex steroid hormones. Lymphocyte subset distribution in peripheral blood and natural killer cell function both have been reported to be under hormonal control. In order to gain more insight into sex steroid hormone action on the immune system, we have measured the lymphocyte subset distribution and natural killer cell activity in 18 men with idiopathic hypogonadotropic hypogonadism before treatment, and after hormonal treatment had normalized plasma testosterone levels. In untreated patients, the mean plasma testosterone concentrations were significantly lower than those in the treated men (3.0 +/- 0.5 nmol/l vs 16 +/- 1.7 nmol/l, p < 0.001). The percentage of peripheral CD3+ lymphocytes, CD8+ cells, the CD4+/CD8+ ratio, and the natural killer cell activity of peripheral mononuclear cells measured in a Cr-51 release assay against target K 562 cells did not differ between patients with idiopathic hypogonadotropic hypogonadism and healthy adults, and most importantly, did not change during hormonal treatment which normalized plasma testosterone levels in the patients. In contrast, the percentage of peripheral CD4+ cells was significantly higher in untreated patients compared with normal adult subjects or patients with idiopathic hypogonadotropic hypogonadism after hormonal treatment that resulted in normal plasma testosterone levels (53 +/- 2 vs 47 +/- 2, p < 0.05). It should be noted that the percentage of peripheral CD16+ cells was significantly lower in untreated men with low plasma testosterone levels than in normal controls. The percentage of CD16+ cells in peripheral venous blood rose significantly after hormonal treatment restored plasma testosterone levels to normal (6 +/- 1 vs 11 +/- 1, p < 0.001). In addition, the percentage of peripheral CD16+ cells correlated significantly with the plasma testosterone levels measured in men with idiopathic hypogonadotropic hypogonadism (r = 0.534, p < 0.001). In conclusion, both the percentage of peripheral CD4+ cells (T-helper lymphocytes) and peripheral CD16+ cells (non-T-non-B cells) are related to the plasma testosterone levels in men with idiopathic hypogonadotropic hypogonadism. These data suggest that in vivo human immune cells are under the regulatory influence of endogenous sex steroids.