Gonadotropin Responses and Metabolism of Synthetic Gonadotropin-Releasing Hormone (GnRH) during Constant Infusion of GnRH in Men and Boys with Delayed Adolescence*

To provide further information on the patterns and amount of gonadotropin-releasing hormone (GnRH) secretion and pituitary responsiveness to presumed physiological and pharmacological concentrations of GnRH, five normal men (27–30 yr) received 4-h infusions of 0 (saline), 10,80, and 800 μg synthetic GnRH randomly at weekly intervals. Four additional men received saline and 10-μg GnRH infusions. For comparison, six boys with delayed adolescence (13–16 9/12 yr) received 200 μg GnRH infusions. Four boys were retested 2 weeks after 100 mg testosterone enanthate were administered im. GnRH concentrations were determined by a highly specific RIA which utilizes Niswender R-42 antiserum and [125I]GnRH purified by Sephadex G-25 chromatography. Sensitivity of this assay is 1 pg/tube or 5 pg/ml plasma. Plasma LH, FSH, and testosterone (T) were determined by RIA. In the men, mean GnRH concentrations during 10-, 80-, and 800-μg infusions were 30 ± 0.2, 207 ± 8.0, and 4030 ± 131 (se) pg/ml. Mean plasma clearance rates of GnRH decreased with increasing doses and were 802 ± 74, 688 ± 53, and 383 ± 47 liters/day ·m2 at 10, 80, and 800 μg GnRH, respectively. At presumed physiological concentrations of GnRH (30–207 pg/ml), significant but not biphasic plasma LH responses occurred during six of the 10-μg infusions and during all 80-μg infusions of GnRH. A biphasic secretory pattern of LH was noted during 800- μg GnRH infusions. Pulsatile secretion of LH was dampened during 10-/ng GnRH infusions as compared with saline infusions. In contrast, striking peaks of LH occurred during 800-μg infusions when plasma GnRH values were greater than 3 ng/ml. Significant but shallow dose-dependent FSH responses were observed. Plasma T increased significantly only during 800-μg infusions. In boys with delayed adolescence, plasma GnRH and plasma clearance of GnRH averaged 1975 ± 90 pg/ml and 380 ± 37 liters/day ·m2 and 1571 ± 272 pg/ml and 460 + 24 liters/day·m2 before and after T therapy. LH responses were significant before and after treatment, but biphasic LH responses were noted only after T administration. Exaggerated FSH responses were observed in all boys before treatment. These responses were greater than the FSH responses of men given 800- μg infusions. These data demonstrate that: 1) absolute responses and patterns of LH and FSH responses are dependent on the dose of GnRH; 2) adult males have a significant LH response to an increment of only 30 pg/ml GnRH, but pulsatile LH release is masked at presumed physiological concentrations of GnRH; and 3) exaggerated FSH responses observed in boys with delayed adolescence may reflect gonadal immaturity. These data plus previous observations (Kelch, R..P., L. E. Clemens, M. Markovs, M. H. Westhoff, and D. W. Hawkins, J Clin Endocrinol Metab40: 53, 1975) suggest that GnRH is secreted episodically in men at maximum concentrations between <30–300 pg/ml.