Allopregnanolone levels decrease after LHRH analogue stimulation test in girls with central precocious puberty

Allopregnanolone (AP), a neuroactive steroid secreted by central nervous system, adrenals, and gonads, plays a role in the development of precocious puberty, as demonstrated by its high baseline levels found in girls with central precocious puberty (CPP). In these patients AP concentrations significantly increase after LHRH stimulation test suggesting its ovarian origin. Aim of this study is to evaluate AP concentrations after LHRH and LHRHa stimulation test in girls with CPP to better establish the secretion source of this neurosteroid.Gonodotropins and steroid hormones were evaluated after LHRH and LHRHa stimulation test in 12 normal weight girls with CPP (PH and B 2-3, 8.06±0.73 yr., first pubertal signs appeared at 7.06±0.71 yr., bone age advanced of 1.91±0.74 yr., and LH levels >5 mUI/ml after both LHRH and LHRHa stimulation).After LHRH stimulation LH, FSH, and AP concentrations significantly increased in all patients. After LHRHa administration LH, FSH, and E2 levels significantly increased, while AP concentrations significantly decreased in all subjects (1.10±0.26, 0.89±0.29 nmol/l; P=0.001). The different response of AP to LHRH (increased levels) and LHRHa (decreased levels) reflect the agonist and antagonist action exerted by these secretagogues. Our data strongly suggest a direct action of LHRHa on ovaries independent of the pituitary, confirming the prevalent ovarian AP production in CPP subjects.