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High Serum Allopregnanolone Levels in Girls with Precocious Puberty

Department of Gynecological, Obstetrics, and Pediatric Sciences, Pediatric Section (L.I., B.P., S.F.), University of Modena and Reggio Emilia, 41.100 Modena, Italy; Department of Obstetrics and Gynecology, University of Siena (L.C., F.P.), 53.100 Siena, Italy; Department of Reproductive Medicine and Child Development, Section of Gynecology and Obstetrics, University of Pisa (S.L.), 56.125 Pisa, Italy; Endocrine Research Unit, National Research Center (M.L.), 56.125 Pisa, Italy; and Department of Pediatrics, University of Parma (S.B.), 43.100 Parma, Italy

Address all correspondence and requests for reprints to: Lorenzo Iughetti, M.D., Pediatrics Department-Policlinico, Via del Pozzo 71, 41.100 Modena, Italy. E-mail: . iughetti.lorenzo{at}unimo.it

Abstract

Allopregnanolone, a circulating neuroactive steroid hormone, is involved in the modulation of behavioral functions, stress, and the neuroendocrine axis. The aim of this study was to evaluate serum allopregnanolone concentrations in girls with central precocious puberty (n = 12), girls with normal pubertal development at the same pubertal stage (n = 17), and prepubertal girls (age-matched; n = 16). Gonadotropin and steroid hormones (allopregnanolone, cortisol, dehydroepiandrosterone sulfate, and E2) were assessed in all patients. GnRH and ACTH stimulation tests were performed in all girls with central precocious puberty and in some pubertal controls. Basal allopregnanolone levels in girls with central precocious puberty were significantly higher than in normal controls (P < 0.01). Allopregnanolone levels increased significantly after GnRH and ACTH stimulation tests (P < 0.05) both in girls with central precocious puberty and in those with normal pubertal development. There was no difference found between the peak values.

In conclusion, our study shows that allopregnanolone is hypersecreted in central precocious puberty, confirming a pubertal stage-related increase in its levels during normal pubertal development. The increase in serum allopregnanolone after GnRH and ACTH stimulation tests demonstrates that both adrenal cortex and gonads are sources of this neuroactive steroid.