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 that 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 boys 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, increased 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 (P3; n = 8) boys, but earlier (0.5-1 h) in adults (P4; n = 10). LH levels remained high for 24 h in P3-P4. Indexes of both the readily releasable and reserve pools of pituitary LH increased significantly with advancing 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 increased significantly in response to nafarelin in stages P2-P4. We conclude that a single dose of the GnRH agonist nafarelin stimulates gonadotropin secretion in normal prepubertal and pubertal males; it also stimulates gonadal steroid production in pubertal males. Pubertal maturation of gonadotrope function appears to involve mainly increases in both the readily releasable and reserve pools of LH. The findings that late pubertal boys had LH responses similar to those of men, but greater T and lesser 17-hydroxyprogesterone outputs are compatible with their pituitary-testicular axis operating at a less downregulated state than 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 puberty. These findings suggest that a single dose of GnRH agonist may provide a simple means of assessing the maturation of the neuroendocrine-testicular axis.