MATURATION OF THE NORMAL PITUITARY-TESTICULAR AXIS, AS ASSESSED BY GONADOTROPIN-RELEASING-HORMONE AGONIST CHALLENGE

Pilot studies in boys with abnormalities of puberty have suggested tha t both gonadotropin and sex steroid responses to GnRH agonist undergo characteristic maturational changes. However, it is not known how the pattern of hormonal secretory responses to GnRH agonist changes during normal puberty. Therefore, we have assessed the responses of normal b oys at various stages of pubertal development to a single dose of the GnRH agonist nafarelin. Baseline LH, FSH, testosterone (T), estradiol (E(2)), and steroid intermediates, including 17-hydroxyprogesterone, i ncreased during puberty. LH responses peaked at 3 h in prepubertal (P1 ; n = 8) and midpubertal (P2; n = 4) boys, at 12 h in late pubertal (P 3; n = 8) boys, but earlier (0.5-1 h) in adults (P4; n = 10). LH level s remained high for 24 h in P3-P4. Indexes of both the readily releasa ble and reserve pools of pituitary LH increased significantly with adv ancing pubertal stage (P < 0.003). FSH responses differed among groups only at 24 h. Nafarelin stimulated T significantly in groups P2 < P3 < P4. The maximal responses of T were 0.54 +/- 0.25 (+/-SEM), 8.7 +/- 2.9, 18.5 +/- 1.0, and 15.3 +/- 1.4 nmol/L in these respective groups (by analysis of variance, F = 40.5; P < 0.001). However, nafarelin did not stimulate E(2) significantly until late puberty; the maximal E(2) responses to nafarelin treatment were 17.9 +/- 5.9, 26.7 +/- 8.7, 318 +/- 71.3, and 329 +/- 17.4 pmol/L in P1, P2, P3, and P4 (F = 18.3; P < 0.001). In contrast to E(2), most intermediate steroids measured inc reased significantly in response to nafarelin in stages P2-P4. We conc lude that a single dose of the GnRH agonist nafarelin stimulates gonad otropin secretion in normal prepubertal and pubertal males; it also st imulates gonadal steroid production in pubertal males. Pubertal matura tion of gonadotrope function appears to involve mainly increases in bo th the readily releasable and reserve pools of LH. The findings that l ate pubertal boys had LH responses similar to those of men, but greate r T and lesser 17-hydroxyprogesterone outputs are compatible with thei r pituitary-testicular axis operating at a less downregulated state th an that of adults. The apparently isolated failure of E(2) to increase in response to nafarelin in early puberty suggests that maturation of aromatase activity normally does not become appreciable until late pu berty. These findings suggest that a single dose of GnRH agonist may p rovide a simple means of assessing the maturation of the neuroendocrin e-testicular axis.