Direct Feedback Inhibition by Endogenous Testosterone on the Pituitary in Man

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Abstract
Synthetic luteinizing hormone-releasing factor (LRF) was injected i.v. into 2 healthy men at successive 1 wk intervals with increasing amounts of LRF from 50-800 .mu.g and the effects on LH [luteinizing hormone] and testosterone titers just before and after successive stimulations were studied. The weekly baseline levels of plasma LH progressively decreased 7 days after administration of increasing amounts of injected LRF. Baseline LH titers fell to the lower portion of the normal range (48 ng/ml) in one man and to under the normal range (29 ng/ml) in the other. Higher peak values of plasma LH (up to 507 and 932 ng/ml) response to LRF occurred within 1 h with increased injected LRF from 50-100 or 200 .mu.g. With larger doses of LRF, the peak values of plasma LH were much lower, as low as 185 and 277 ng/ml. These titers were close to the basal normal range. Weekly baseline titers of testosterone increased markedly following increased LRF. Peak plasma testosterone levels occurred within 180 min of each LRF stimulation. Testosterone titers 24 h after stimulation remained elevated on each occasion. Baseline LH titers fell inversely with increases in the weekly baseline testosterone levels. The peak rises of LH were lower with larger doses of LRF when baseline plasma testosterone titers exceeded certain levels. These preliminary data suggest that single weekly injections of LRF have prolonged actions in raising testosterone and endogenous testosterone may inhibit pituitary responses to LRF.