Differential Sleep-Wake Sensitivity of Gonadotropin-Releasing Hormone Secretion to Progesterone Inhibition in Early Pubertal Girls

Abstract

Context: Early pubertal luteinizing hormone (LH), and by inference gonadotropin-releasing hormone (GnRH), pulse secretion is marked by high nocturnal but low daytime frequency; however, the underlying mechanisms remain unclear. Plasma concentrations of progesterone, the major regulator of GnRH frequency in women, increase in the early morning in early pubertal girls and may help slow daytime GnRH frequency. Objective: To evaluate the effect of progesterone on LH pulse frequency in early to mid-pubertal girls. Design: Controlled interventional study. Setting: General clinical research center. Participants: Eighteen non-obese, non-hyperandrogenemic Tanner 1–3 girls. Intervention: Twelve-hour (19:00–07:00 h) blood sampling with or without oral progesterone administration (25–50 mg at 16:00 and 20:00 h). Main Outcome Measure: LH pulse frequency. Results: Girls receiving progesterone (n = 5) exhibited lower 12-hour LH pulse frequency than controls (n = 13), but this difference was not statistically significant (average interpulse intervals 196.0 ± 61.9 and 160.4 ± 67.1 min, respectively; p = 0.2793). In contrast to controls, however, girls receiving progesterone exhibited no LH pulses during waking hours (19:00–23:00 h; estimated interpulse interval 326.0 ± 52.7 vs. 212.0 ± 120.9 min; p = 0.0376), while nighttime (23:00–07:00 h) interpulse intervals were similar (174.8 ± 62.0 vs. 167.5 ± 76.9 min, respectively; p = 0.7750). Conclusions: Exogenous progesterone acutely suppressed daytime, but not nocturnal, LH pulse frequency in early to mid-pubertal girls, suggesting that GnRH pulse frequency is differentially regulated by progesterone depending on sleep status.