TY - JOUR
T1 - Patterns of pulsatile luteinizing hormone and follicle-stimulating hormone secretion in prepubertal (midchildhood) boys and girls and patients with idiopathic hypogonadotropic hypogonadism (Kallmann's syndrome): A study using an ultrasensitive time-resolved immunofluorometric assay
AU - Wu, F C
AU - Butler, G E
AU - Kelnar, C J
AU - Stirling, H F
AU - Huhtaniemi, I
N1 - Fm319 Times Cited:97 Cited References Count:33
PY - 1991/6
Y1 - 1991/6
N2 - To study the ontogeny of spontaneous pulsatile LH and FSH secretion before the onset of puberty, plasma LH and FSH were measured by an ultrasensitive time-resolved immunoflurometric assay in 16 boys and 6 girls, aged 6.5 ± 0.2 yr (±SEM; range, 4.4-8.0) with short stature. Eight male patients with idiopathic hypogonadotropic hypogonadism (Kallmann's syndrome), aged 24.1 ± 3.4 yr, were also investigated. Blood samples were withdrawn at 10- to 20-min intervals for 12 h from 2000-0800 h. Pituitary responsiveness was assessed by a standard iv LHRH challenge test. LH and/or FSH pulses were detectable in all but two prepubertal subjects. In boys, low amplitude LH (0.16 ± 0.06 U/L) and FSH (0.19 ± 0.03 U/L) pulses were detectable at mean frequencies of 2.19 ± 0.37 and 2.13 ± 0.46 pulses/12 h, respectively. In girls, low amplitude LH (0.29 ± 0.18 U/L) pulses, but higher (P <0.05 compared to boys) amplitude FSH (1.62 ± 1.05 U/L) pulses were observed at frequencies of 1.71 ± 0.56 and 1.67 ± 0.53 pulses/12 h, respectively. Mean FSH in prepubertal girls (1.95 ± 0.88 U/L) was significantly (P <0.05) higher than that in boys (0.46 ± 0.07 U/L), but mean LH was not different at 0.17 ± 0.07 and 0.10 ± 0.03 U/L, respectively. Patients with Kallmann's syndrome had mean LH and FSH levels indistinguishble from those of prepubertal boys. Nocturnal augmentation of pulsatile LH or FSH secretion was observed in 74% of children (71% in girls and 75% in boys), but in none of the eight patients with Kallmann's syndrome. A close temporal association was observed between sleep onset and the appearance of nocturnal pulsatile gonadotropin secretion. The FSH response to exogenous LHRH in prepubertal girls was significantly greater than that in patients with Kallmann's syndrome and prepubertal boys, but LH responses were not different. Our results show that pulsatile LH and FSH secretion occurs in the majority of boys and girls in midchildhood, with a robust association with nocturnal sleep onset. Between the ages of 4-8 yr, these low amplitude and low frequency pulses are unable to activate gonadal function. The regulation of FSH secretion in prepubertal girls appears to be different from that in prepubertal boys. Taken together with our previous results in older peripubertal boys, the onset of puberty appears to be presaged by the gradual emergence, after the age of 8 yr, of a window of sleep-entrained nocturnal LH pulses of increasing amplitude and frequency, which is encompassed within a preexisting diurnal rhythm. These changes reflect the progressive accentuation of hypothalamic LHRH discharge and may constitute the rate-limiting steps toward the initiation of puberty.
AB - To study the ontogeny of spontaneous pulsatile LH and FSH secretion before the onset of puberty, plasma LH and FSH were measured by an ultrasensitive time-resolved immunoflurometric assay in 16 boys and 6 girls, aged 6.5 ± 0.2 yr (±SEM; range, 4.4-8.0) with short stature. Eight male patients with idiopathic hypogonadotropic hypogonadism (Kallmann's syndrome), aged 24.1 ± 3.4 yr, were also investigated. Blood samples were withdrawn at 10- to 20-min intervals for 12 h from 2000-0800 h. Pituitary responsiveness was assessed by a standard iv LHRH challenge test. LH and/or FSH pulses were detectable in all but two prepubertal subjects. In boys, low amplitude LH (0.16 ± 0.06 U/L) and FSH (0.19 ± 0.03 U/L) pulses were detectable at mean frequencies of 2.19 ± 0.37 and 2.13 ± 0.46 pulses/12 h, respectively. In girls, low amplitude LH (0.29 ± 0.18 U/L) pulses, but higher (P <0.05 compared to boys) amplitude FSH (1.62 ± 1.05 U/L) pulses were observed at frequencies of 1.71 ± 0.56 and 1.67 ± 0.53 pulses/12 h, respectively. Mean FSH in prepubertal girls (1.95 ± 0.88 U/L) was significantly (P <0.05) higher than that in boys (0.46 ± 0.07 U/L), but mean LH was not different at 0.17 ± 0.07 and 0.10 ± 0.03 U/L, respectively. Patients with Kallmann's syndrome had mean LH and FSH levels indistinguishble from those of prepubertal boys. Nocturnal augmentation of pulsatile LH or FSH secretion was observed in 74% of children (71% in girls and 75% in boys), but in none of the eight patients with Kallmann's syndrome. A close temporal association was observed between sleep onset and the appearance of nocturnal pulsatile gonadotropin secretion. The FSH response to exogenous LHRH in prepubertal girls was significantly greater than that in patients with Kallmann's syndrome and prepubertal boys, but LH responses were not different. Our results show that pulsatile LH and FSH secretion occurs in the majority of boys and girls in midchildhood, with a robust association with nocturnal sleep onset. Between the ages of 4-8 yr, these low amplitude and low frequency pulses are unable to activate gonadal function. The regulation of FSH secretion in prepubertal girls appears to be different from that in prepubertal boys. Taken together with our previous results in older peripubertal boys, the onset of puberty appears to be presaged by the gradual emergence, after the age of 8 yr, of a window of sleep-entrained nocturnal LH pulses of increasing amplitude and frequency, which is encompassed within a preexisting diurnal rhythm. These changes reflect the progressive accentuation of hypothalamic LHRH discharge and may constitute the rate-limiting steps toward the initiation of puberty.
KW - sleep-wake patterns
KW - gonadotropin-secretion
KW - testosterone release
KW - pubertal children
KW - lh
KW - algorithms
KW - men
U2 - 10.1210/jcem-72-6-1229
DO - 10.1210/jcem-72-6-1229
M3 - Article
SN - 1945-7197
VL - 72
SP - 1229
EP - 1237
JO - J Clin Endocrinol Metab
JF - J Clin Endocrinol Metab
IS - 6
ER -