Disappearance of biologic activity of synthetic LRH in normal and hypogonadal men

The disappearance rates of the biologic activity of synthetic LRH have been measured in normal and hypogonadal men before and during estrogen treatment. Biologic activity was assayed by the change in radioimmunoassayable rat LH levels induced by injection of human plasma into ovariectomized rats pretreated with estrogen and progesterone, and compared with a dose-response curve using synthetic LRH. Following rapid iv injection of 100 micrograms synthetic LRH, peripheral blood peak levels of biologic activity occurred in less than 2-6 minutes, and the disappearance curve contained 2 exponential components. In 3 normal men the initial component had a t1/2 of 2 minutes and the second component a t1/2 of 10 minutes. Six hypogonadal men had first and second components of disappearance no different from normals whether or not they responded to LRH injection with increased endogenous hLH. While diethylstilbestrol 2 mg orally for 7 days suppressed pituitary hLH response to exogenous synthetic LRH (mean max.deltahLH 236 VS 46 NG/ml), it did not alter the disappearance rates in normal or hypogonadal men. These studies show that the biologic activity of synthetic LRH disappears from the blood after iv administration at rates similar to radioimmunoassayable and radioactive-labeled LRH. They further suggest that the lack of pituitary responsiveness to LRH in hypogonadal and estrogen-treated men is not due to more rapid clearance of the releasing hormone.