Differential effects of aging on activin A and its binding protein, follistatin, across the menopause transition.

To assess the involvement of ovarian-derived regulatory proteins in FSH modulation, we compared FSH, inhibin A, inhibin B, activin A, and follistatin (FS) in 79 women from the following five groups: young cycling, older cycling, perimenopause (PERI), spontaneous menopause (PM), and surgical menopause receiving estrogen (OVX+ET). Although inhibin B varied as expected by ovarian function, no group differences were observed in activin A, barring a tendency for an increase in PERI, while FS 288 was lower in the PERI, PM, and OVX+ET groups and negatively correlated with advancing age.

Diurnal changes in FSH-regulatory peptides and their relationship to gonadotrophins in pubertal girls.

BACKGROUND: FSH-regulatory peptides participate with GnRH and sex steroids to regulate serum FSH concentrations. We hypothesized that day/night variations in FSH serum concentrations would be associated with diurnal variation in FSH-regulatory peptides. METHODS: Blood was obtained every 15 min for 24 h beginning at 08:00 h in eight girls [seven with variations in growth or puberty and one with idiopathic hypogonadotrophic hypogonadism (IHH)] and for 12 h beginning at 20:00 h in 12 additional girls with variant puberty, eight with gonadal dysgenesis or ovarian failure (GD/OF) and one with IHH. Samples across 3 h blocks were pooled for determination of LH, FSH, activin-A, inhibin-B and follistatin 288. RESULTS: LH and FSH concentrations increased from 23:00 to 08:00 h with respect to daytime concentrations in pubertal girls (P<0.005) but only LH increased (P=0.002) in girls with GD/OF. In pubertal girls, inhibin-B declined during the day (P=0.019), reaching a nadir between 17:00 and 22:45 h just prior to the night-time increase in FSH. Follistatin concentrations exhibited diurnal variation (P=0.028), with the greatest concentrations occurring between 05:00 and 11:00 h. Activin-A concentrations declined coincident with the night-time increase in FSH in pubertal girls (P<0.0001) but not in girls with GD/OF. CONCLUSIONS: The directionality of changes in FSH-regulatory proteins supports the notion that FSH-regulatory peptides may contribute to the night-time augmentation of circulating FSH during puberty in girls.

GnRH agonist stimulation of the pituitary-gonadal axis in children: age and sex differences in circulating inhibin-B and activin-A.

BACKGROUND: Inhibin-B decreases and activin increases FSH secretion in adults. We investigated whether an FSH-inhibin/activin feedback loop exists before or during puberty. METHODS: FSH secretion was stimulated with 10 microg/kg leuprolide acetate (GnRH agonist) in 18 girls, ages 1.0-13.2 years, and 11 boys, ages 8.9-15.2 years, with variations in pubertal development, and in five normal 9- to 10-year-old girls. Blood, obtained at 0, 0.5, 1, 2, 4, 8, 12, 16, 20 and 24 h after GnRH agonist, was analysed for LH, FSH, activin-A, inhibin-A, inhibin-B, follistatin 288 and estradiol/testosterone. RESULTS: FSH increased within 30 min of GnRH agonist administration with a peak greater in girls than boys (P=0.0006). Baseline inhibin-B was greater in boys than girls (P=0.01), while baseline activin-A concentrations were greater in girls. GnRH agonist-stimulated FSH increased inhibin-B in girls by 8 h and in boys by 20 h (P<0.05), but did not affect activin-A. Inhibin-B increases were seen only in girls older than 5 years. CONCLUSIONS: An inhibin-B-FSH feedback loop exists prior to the onset of puberty in girls older than 5 years. Sex differences in activin-A and inhibin-B concentrations may be responsible for sex differences in serum FSH concentrations.

Sex differences in FSH-regulatory peptides in pubertal age boys and girls and effects of sex steroid treatment.

BACKGROUND: FSH concentrations are higher in girls than in boys before puberty. We hypothesized that steroid-mediated changes in FSH-regulatory proteins underlie the sex differences in FSH secretion and pubertal timing. METHODS: FSH-regulatory proteins, LH, FSH and sex steroids were measured in five boys, 10 girls, and five girls with Turner syndrome before and during sex steroid treatment (girls, 0.05 mg/day estradiol; boys, 5 mg/day testosterone) for up to 4 weeks. Blood was obtained every 15 min from 20.00 to 08.00 h before and during sex steroid treatment. RESULTS: The mean FSH concentration was higher in girls than in boys (P = 0.0044). Activin-A concentrations were greater (P < 0.0001) and inhibin-B concentrations lower (P < 0.0001) in girls compared with boys. Steroid treatment (i) suppressed LH/FSH concentrations in all subjects; (ii) increased the mean activin-A concentration in all but the Turner girls (P = 0.001); and (iii) decreased inhibin-B concentrations in boys (P = 0.005) but not in girls. Total follistatin and follistatin 288 concentrations did not differ by sex. CONCLUSIONS: Sex steroids regulate circulating activin-A and inhibin-B concentrations in children. The lower inhibin-B and higher activin-A concentrations may explain the higher FSH and earlier onset of puberty in girls.

Incomplete modified fast in obese early pubertal girls leads to an increase in 24-hour growth hormone concentration and a lessening of the circadian pattern in leptin.

We studied nutrition and GH in eight obese girls, aged 6-11 yr. Blood was sampled every 15 min for 24 h. A 48-h diet providing 25% of assumed caloric needs was imposed, with repeat sampling during the last 24 h. Six nonfasting lean girls were also studied, and their mean GH was 3 times that of the obese girls in the fed state (P = 0.024). Dieting increased mean GH by 60% (P = 0.0028). There was no difference in pulse number for either group, but total secretion for lean girls was 3.9 times greater than that in obese girls during the fed state. With dieting, obese girls increased their total GH secretion by 60% (P = 0.010), but maintained lower total secretion, approximately 40% that of lean girls (P = 0.014). Mean leptin in obese girls in the fed state was 6.2 times greater than mean leptin in lean girls (P = 0.0001), with higher concentrations at night (P < 0.05) and lowering of total mean leptin while dieting. We conclude that in early pubertal obese girls, short-term caloric restriction partially reverses the low GH state that is characteristic of obesity. The change is concomitant with a decrease in leptin and a lessening of circadian differences.