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.