Sleep Modulation of Neuroendocrine Function: Developmental Changes in Gonadotropin-Releasing Hormone Secretion during Sexual Maturation

Abstract

ABSTRACT. To assess sleep-associated changes in gonadAbbreviations otropin-releasing hormone secretion during sexual maturation, we studied nighttime and daytime patterns of LH and FSH secretion in two groups with qualitatively similar sex steroid levels: girls with central precocious puberty and young adult women in the early follicular phase of an ovulatory menstrual cycle. In the girls with central precocious puberty, all indices of LH secretion were significantly higher at night than during the day (mean L H levels, 12 f 2 versus 5 f 1 IUIL, p 5 0.01; LH pulse amplitude 16 f 2 versus 7 f 1 IU/L, p 5 0.01; and LH pulse frequency 0.70 f 0.05 versus 0.35 f 0.08 pulselpatient-h, p 5 0.01).Girls with a history of menses, who were presumably the most mature, lacked this diurnal variability. Mean nocturnal FSH levels were only slightly higher than daytime levels (7.6 f 0.5 versus 7.2 f 0.5 IU/L, p 5 0.05) resulting in alternating periods of L H (nighttime) and FSH (daytime) predominance in this pubertal population. In contrast, the adult women had lower mean gonadotropin levels and LH pulse frequencies at night than during the day (mean LH 7 f 1 versus 10 f 1 IUIL, p 5 0.05; mean FSH 9 f 1 versus 10 f 1 IUIL, p 5 0.05; LH pulse frequency 0.40 f 0.08 versus 0.70 f 0.10 pulse/patient-h, p 5 0.05) and often (six of eight) demonstrated striking suspension of gonadotropin-releasing hormone secretion during sleep. The smaller changes in FSH again resulted in periods of relative LH (daytime) and FSH (nighttime) predominance.GnRH, gonadotropin-releasing hormone CPP, central precocious puberty EFP, early follicular phase DSIP, delta sleep-inducing peptide Sleep is an important neuroendocrine modulator of hypothalamic function. With the onset of puberty, a marked increase in sleep-entrained, GnRH-induced gonadotropin pulses occurs (1). After complete maturation of the reproductive axis, cyclic changes in hypothalamic-pituitary-gonadal axis function result in serum estradiol levels during the EFP of the menstrual cycle that approximate those of girls during puberty. Despite this comparable gonadal steroid milieu, women in the EFP exhibit a strikingly different response to sleep. In contrast to pubertal girls, women in the EFP demonstrate sleep-associated slowing in the frequency of GnRH-induced gonadotropin secretory events (2, 3). To further explore the changing impact of sleep upon neurosecretory dynamics across development, we examined the nighttime and daytime patterns of gonadotropin secretion in 39 girls with idiopathic CPP and contrasted them with those of eight young adult women studied during the EFP of an ovulatory cycle. MATERIALS AND METHODSWhen between-group comparisons were made, the girls with central precocious puberty differed significantly fromPatients. Thirty-nine girls with idiopathic CPP were studied as described below. Patients with neurogenic precocity (i.e. centrally the women in the early follicular phase with respect to mediated precocious puberty with radiographic evidence of a each index gonadotrop...

Absence of Apparent Circadian Rhythms of Gonadotropins and Free α-Subunit in Postmenopausal Women: Evidence for Distinct Regulation Relative to Other Hormonal Rhythms

“…However, because of the superimposed effects of sleep on these hormones, it is less clear that the 24-h excursions of gonadotropin and gonadal hormone levels in men and women represent a true circadian rhythm. Nighttime augmentation of gonadotropin levels is a hallmark of puberty (Boyar et al, 1972;Kapen et al, 1974;Landy et al, 1990;Wu et al, 1996). However, sleep-reversal studies have shown that this is due to the stimulatory effect of sleep on LH secretion rather than to a true circadian effect (Kapen et al, 1974).…”

“…However, as is the case with a number of other hormonal systems such as growth hormone (GH) and PRL (Czeisler and Klerman, 1999;Van Cauter et al, 2001), sleep has a profound influence on reproductive hormone secretion. There is a sleep-associated increase in pulsatile luteinizing hormone (LH) secretion during puberty in boys and girls (Boyar et al, 1972;Kapen et al, 1974;Landy et al, 1990;Wu et al, 1996) as well as in adult men (Luboshitzky et al, 2001;Schiavi et al, 1992;Veldhuis et al, 2000) and a sleep-associated slowing of pulsatile LH secretion in young women that is most notable in the early follicular phase (Filicori et al, 1986;Hall et al, 1992;Hall et al, 2005;Rossmanith et al, 1993;Soules et al, 1985). Twenty-four-hour diurnal rhythms of follice-stimulating hormone (FSH) (Mortola et al, 1992) and LH have been documented in the setting of normal sleep/ wake routines.…”