Correlation of Luteinizing Hormone-Releasing Factor-Induced Luteinizing Hormone and Follicle-Stimulating Hormone Release from Infancy to 19 Years with the Changing Pattern of Gonadotropin Secretion in Agonadal Patients: Relation to the Restraint of Puberty *

Basal and LRF-stimulated plasma LH and FSH levels were assessed in longitudinal and cross-sectional studies in 37 subjects, aged 6 months to 19 yr, with gonadal dysgenesis or other forms of functional agonadism. In both groups of patients under 5 yr of age, mean basal and LRF-induced gonadotropin levels were significantly increased over normal levels. In patients with gonadal dysgenesis between 5–11 yr of age, the mean basal concentrations of FSH and LH and the mean LRFevoked gonadotropin responses were significantly less than the mean values for agonadal children <5 yr of age and, with the exception of mean basal LH, exceeded levels for normal prepubertal children. However, in some patients between 5–11 yr of age, both the basal concentrations of serum gonadotropins and the LH and FSH responses to LRF were comparable to results in normal prepubertal children. Hence, in this age group, the basal concentrations of LH and FSH and the response to LRF in agonadal patients may not provide definitive evidence of defective or absent testes or ovaries. After 11 yr of age, a striking rise in both basal and readily releasable LH and FSH occurred. The data suggest that in agonadal patients the diphasic pattern of gonadotropin secretion and readily releasable FSH and LH (high in infancy and early childhood, low in midchildhood, and again rising to high levels in the adult castrate range at about age 11 yr) 1) reflects maturational changes in the central nervous system (CNS) regulation of gonadotropin secretion independent of gonadal sex steroids, 2) provides further evidence that the hypothalamic-pituitary-gonadal negative feedback mechanism is operative in infancy, and 3) supports the action of a CNS inhibitory mechanism (a component independent of gonadal feedback influences) which restrains gonadotropin synthesis and secretion and inhibits puberty during the interval between early childhood and puberty and which is inhibited or suppressed at the onset of puberty. We postulate that the CNS mediates these maturational changes in the patterns of gonadotropin secretion of agonadal as well as normal infants and children by modulating the synthesis and pulsatile release of LRF.