On the role of dihydrotestosterone in regulating luteinizing hormone secretion in man

The effect of dihydrotestosterone [17 beta-hydroxy-5 alpha-androstone-3-one (DHT) in the negative regulation of LH was studied throughout 3 months of percutaneous administration of this steroid to six normal male volunteers and six patients with primary testicular hypogonadism. In addition, testosterone (T) was administered according to the same protocol to the six hypogonadal patients. Plasma T, DHT, estradiol, sex hormone-binding globulin, and LH levels were measured by RIA before and weekly during treatment. In normal men, plasma DHT rose regularly from 0.5 +/- 0.2 to 3.3 +/- 0.9 ng/ml after 3 months of treatment. Concurrently, T decreased from 5.5 +/- 2.0 to 2.9 +/- 0.3 ng/ml, and sex hormone-binding globulin levels decreased from 1.2 +/- 0.1 to 0.9 +/- 0.05 mg/liter. Mean basal LH levels remained stable between 1.9 +/- 1.3 and 3.1 +/- 1.1 mIU MRC, LH 68/40 per ml throughout treatment. In hypogonadal men after DHT treatment, basal LH levels were not suppressed. In contrast, after T administration, plasma LH decreased from 19.8 +/- 5.4 mIU/ml to normal levels (3.4 +/- 2.7 mIU/ml). From these studies, we conclude that 1) high levels of plasma DHT, maintained over a long period, were unable to lower plasma LH in either normal or hypogonadal patients, and 2) in contrast, during the same length of time, high levels of plasma T were perfectly capable of achieving feedback regulation of LH secretion. From these data, it seems unlikely that circulating DHT plays an important role in the physiological regulation of LH secretion.