Bioactive Luteinizing Hormone Pituitary Reserves during Normal and Abnormal Male Puberty*

We explored the possibility that evaluation of serum bioactive LH (B-LH) reserves in response to an intensive (high dose; 4 h) gonadotropin-releasing hormone (GnRH) infusion might provide additional insight into normal and abnormal pubertaJ maturation. Controls consisted of 24 boys and 10 men; 10 hypopituitary cases (11–53 yr of age) were studied. Maturation was staged by morning testosterone levels, as well as clinically. B-LH was assayed by rat Leydig cell testosterone production; immunoreactive LH (I-LH) was assayed by RIA. In control individuals, B-LH reserve was related to maturational stage in a biphasic manner (cubic fit r = 0.85): 1) B-LH reserve is minimal in many prepubertal children (showing no clear increase in the youngest boy), 2) B-LH undergoes an initial rise as testosterone increases from 5 to 50 ng/dl (P<0.05), 3) B-LH peaks at a testosterone level of 216 ng/dl, and 4) B-LH then declines modestly (P<0.05) as the testosterone level rises further. Though the initial rise in LH was seen in I-LH data, this full pattern was not. The pubertal peak was evident in the B-LH to 1-LH ratio. Gonadotropin-releasing hormone-stimulated B-LH and I-LH both correlated with the maturation achieved by hypogonadotropic males, and discriminated teenagers with delayed puberty from those with gonadotropin deficiency once testosterone levels exceeded 30 ng/dl. This is a testosterone level which occurs late prepuberty, very early puberty, or adrenarche. These data indicate that the pituitary B-LH reserve is greater during midpuberty than before or after this time. Whether the pubertal peak in the ratio of B-LH to I-LH indicates a change in LH biopotency remains to be determined. Furthermore, the normal biphasic relationship of B-LH reserve to the baseline testosterone level provides an additional diagnostic criterion for distinguishing delayed puberty from hypogonadotropinism.