Differential effect of single high dose and divided small dose administration of human chorionic gonadotropin on Leydig cell steroidogenic desensitization.
This study compared the effect of a single high dose of hCG (1500 IU) with that of the same dose administered in multiple small doses (300 IU, once daily for 5 days) on Leydig cell steroidogenesis. Administration of a single high dose of hCG to seven healthy men raised the mean plasma testosterone (T) level to peak levels 2.1 +/- 0.2 (SEM) X the baseline value at 48 h. Thereafter plasma T decreased to below normal (0.7 +/- 0.1 X baseline) 7 days after the injection. The mean 17-hydroxyprogesterone (17-OHP) level peaked at 24 h (2.5 +/- 0.2 X baseline) and then also fell to a nadir value of 0.6 +/- 0.2 X baseline on day 7. Reflecting the early accumulation of 17-OHP over T, the 17 OHP/T ratio reached its maximum (1.6 +/- 0.1 X baseline) at 24 h at the same time when plasma estradiol [(E2) 4.4 +/- 0.6 X baseline] and the ratio E2/T (2.7 +/- 0.3 X baseline) achieved their maximal values. Administration of 1500 IU hCG in five divided doses of 300 IU daily increased the mean plasma T levels to peak value of 2.1 +/- 0.2 X baseline at 5 days and the levels remained elevated thereafter. The response of T as reflected by the area under the curve was almost twice as great as in the single dose study (2844 +/- 360 vs. 1647 +/- 214). In contrast to the single high dose experiment, mean plasma 17-OHP levels in the divided dose protocol did not peak at 24 h but only gradually increased. As the increase of T exceeded the 17-OHP increase at almost all time intervals, no accumulation of 17-OHP over T occurred as in the single dose experiment. Instead the 17-OHP/T ratio fell to a nadir value of 0.6 +/- 0.1 X baseline on day 7. The initial E2 peak was absent in the divided dose protocol and the E2/T ratio only marginally increased. Considering both experiments together a close relation was found between the hCG-induced increases in E2 and 17-OHP (r = +0.88, P less than 0.001), as well as the ratio 17 OHP/T (r = +0.64, P less than 0.02).(ABSTRACT TRUNCATED AT 400 WORDS)
D019326:17-alpha-Hydroxyprogesterone; D000293:Adolescent; D000328:Adult; D006063:Chorionic Gonadotropin / Q000008:administration & dosage* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000097:blood; D006801:Humans; D006908:Hydroxyprogesterones / Q000097:blood; D007985:Leydig Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013256:Steroids / Q000096:biosynthesis*; D013739:Testosterone / Q000097:blood
D006063:Chorionic Gonadotropin; D006908:Hydroxyprogesterones; D013256:Steroids; D013739:Testosterone; D004958:Estradiol; D019326:17-alpha-Hydroxyprogesterone