Ontogeny of pulsatile gonadotrophin secretion and pituitary responsiveness in male puberty in man: a mixed longitudinal and cross-sectional study

Abstract

The onset of puberty is characterized by a sleep-associated increase in pulsatile LH secretion which is not observed in adults. The ontogeny of gonadotrophin secretion during pubertal maturation may reflect changes in endogenous LHRH secretion, pituitary sensitivity to LHRH and/or alterations in gonadal steroid feedback. To understand the interplay between these mechanisms, we have examined the pulsatile pattern of plasma LH, FSH, testosterone, oestradiol and prolactin between 20.00 and 09.00 h and the pituitary response to repeated exogenous LHRH stimulation in 16 boys with delayed puberty (age 16.3 +/- 2.7 (S.E.M.) years) on one to four occasions in a mixed longitudinal/cross-sectional analysis. Physical maturity was determined by Tanner G staging (1-5) and clinical progress followed for a mean duration of 22.4 +/- 8.5 months during which 33 hormone profiles were obtained. Nocturnal (23.00-09.00 h) LH pulse frequency increased to a peak of 0.54 +/- 0.03/h at stage 2 which was followed by a gradual decline to 0.42 +/- 0.04/h at stage 5. The appearance of LH pulses in the evening (20.00-23.00 h), probably representative of the rest of the day, was delayed until mid-puberty from which point frequency increased to a peak of 0.53 +/- 0.08/h at stage 5. LH pulse amplitude showed a linear increase from stages 1 to 5, with nocturnal pulse amplitudes being higher than evening pulses throughout. FSH did not show a clear pulsatile pattern. The LH:FSH ratio reversed from less than 1 to greater than 1 at stage 2. The LH response to exogenous LHRH increased in parallel with LH pulse amplitude. There was no difference in the pattern of LH response to repeated LHRH stimulation as puberty advanced; the first stimulus always elicited a greater response than subsequent doses. In contrast, the FSH response to LHRH was maximal at stage 1 and became attenuated thereafter. The estimated mean nocturnal LHRH concentration or amplitude did not show any increase during pubertal maturation from 20.42 +/- 11.57 at stage 1 to 35.96 +/- 20.83 ng/l at stage 5. In conclusion, the sequential changes in this study suggest that the sleep-entrained increase in LHRH pulse frequency plays a key role at the onset of puberty. By enhancing pituitary responsiveness and setting in motion a cascade of events, this peripubertal augmentation of LHRH pulse frequency can account for most of the subsequent changes in LH, FSH and testosterone secretion during pubertal development in the male without any apparent alteration in LHRH pulse amplitude.