LH AND FSH RESPONSES TO LUTEINIZING-RELEASING HORMONE IN NORMAL, ADULT, HUMAN MALES

Time-response and dose-response relationships were established for the LH [luteinizing hormone] and FSH [follicle stimulating hormone] response to single i.v. bolus injections of synthetic LRH [luteinizing hormone releasing hormone]. Sixteen normal adult human males, ages 19-45 were studied, and 80 individual tests were performed using a broad range of LRH doses from 0-3000 .mu.g. Serum gonadotropins were measured at frequent intervals ranging from -30 to 180 min after LRH injection. The curves describing changes in blood LH and FSH with time were not superimposable at any dose level. The 50% decay time for the LH response showed a significant linear log-dose relationship to LRH. For LH, dose-response relationships existed for both, the peak LH release and the total LH secretion (area under the time-response curve). No minimal or maximal effective doses were reached for LH within the dose range from 1 to 3000 .mu.g LRH. The smallest dose (measured as peak LH concentration), that produced a response significantly different from saline injections was 1.58 .mu.g/subject; judged by total LH secretion (area under the time-response curve) the smallest dose producing a significant response was 2.39 .mu.g/subject. No dose-response relationship existed for the peak FSH release. Judged by total FSH secretion (area under the time-response curve), the effects of LRH were dose related; the smallest effective dose was 20 .mu.g LRH. As for LH, no maximal effective dose was reached within the dose range studied. The 95% confidence intervals for the peak responses to an i.v. bolus injection of 100 .mu.g synthetic LRH were 400%-800% of the individual mean base line LH concentration, and 100%-200% of the individual mean base line FSH concentration. Serum testosterone did not change significantly in response to single bolus injections of LRH at any of the dose levels studied. The peak LH responses to any dose of LRH were positively correlated to the individual mean base line LH concentrations. No correlations were observed between the peak LH or FSH responses and age, race, marital status, body weight, or body surface area of the subjects. In a 2nd series of studies, a 2 h, constant infusion of synthetic LRH was administered at 5 different infusion rates (doses) to 4 normal adult human males for a total of 20 infusions. Serum LH and FSH responses were sustained at dose related levels characteristic of each individual during the entire LRH infusion period. In contrast to the lack of testosterone responses to bolus injections of LRH, serum testosterone rose significantly in response to all dose levels of LRH infusion. These are the most extensive pharmacologic studies of LRH-LH and LRH-FSH relations in man yet reported.