Steroids 70 (2005) 725–731 Low serum allopregnanolone levels in girls with precocious pubarche Lorenzo Iughetti a,∗ , Barbara Predieri a , Stefano Luisi b , Elena Casarosa c , Sergio Bernasconi d , Felice Petraglia b a DepartmentofPediatrics,UniversityofModenaandReggioEmilia,ViadelPozzo,71,41100Modena,Italy b DepartmentofPediatrics,ObstetricsandReproductiveMedicine,ChairofObstetricsandGynecology,UniversityofSiena,53100Siena,Italy c DepartmentofReproductiveMedicineandChildDevelopment,SectionofGynecologyandObstetrics,UniversityofPisa,56126Pisa,Italy d DepartmentofPediatrics,UniversityofParma,43100Parma,Italy Received 19 March 2004; received in revised form 2 February 2005; accepted 29 March 2005 Available online 11 May 2005 Abstract Allopregnanolone, a neuroactive steroid, increases during pubertal development and high concentrations are present in subjects with precocious puberty. The aim of the present study was to evaluate serum allopregnanolone levels in girls with precocious pubarche (PP). Basal gonadotropins and steroid hormones were assessed in 17 girls with PP, 22 girls with central precocious puberty (CPP), 25 girls with normal puberty at the same pubertal stage of CPP ones, and 17 prepubertal girls. Adrenocorticotropin hormone (ACTH) and gonadotropin-releasing hormone (GnRH) stimulation tests were performed in all subjects with PP, and in 12 out of 22 with CPP. All girls with normal puberty underwent to GnRH test, while ACTH test was performed in 17 out of 25. Basal dehydroepiandrosterone sulfate (DHEAS) concentrations resulted significantly higher in PP and normal pubertal girls than in prepubertal ones. Allopregnanolone, gonadotropins and estradiol levels were significantly lower in PP group with respect to CPP (P < 0.05), while they were comparable among PP, normal pubertal and prepubertal groups. After ACTH administration, allopregnanolone concentrations significantly increased in all groups (P < 0.05). After GnRH stimulation, its levels significantly increased in CPP and normal pubertal controls (P < 0.05), while no incremental rise was found in PP girls. In conclusion, our study shows that in girls with PP basal and GnRH-stimulated levels of allopregnanolone are significantly lower than in CPP girls. These data suggest that this neurosteroid may be considered a new marker of pubertal development. © 2005 Elsevier Inc. All rights reserved. Keywords: Neurosteroids; Allopregnanolone; Adrenal androgen; Precocious pubarche; Central precocious puberty; Girls 1. Introduction Over the past decade, it has become clear that brain, like gonads, adrenals and placenta, is a steroidogenic organ. The steroids synthesized de novo from cholesterol in the central nervous system (CNS), named neuroactive steroids or neuros- teroids, have a wide variety of functions [1]. In general, they act not through classic steroid hormone nuclear receptors, but through other mechanisms such as ion gated neurotrans- mitter receptors, or direct/indirect modulation of other neu- rotransmitter receptors [2–4]. Several studies demonstrated that some steroid hormones synthesized in the brain and in ∗ Corresponding author. Tel.: +39 059 4222182; fax: +39 059 4224583. E-mailaddress: iughetti.lorenzo@unimore.it (L. Iughetti). other steroidogenic organ are among the most selective, po- tent, and efficacious allosteric modulators of -aminobutyric acid A (GABA A ) receptors identified to date, with potency and efficacy similar to or even greater than those of benzodi- azepines and barbiturates [2,5]. The most extensively studied neurosteroids are the sedative–hypnotic 3-hydroxy ring A-reduced pregnane steroids, including allopregnanolone (3-hydroxy-5-pregn- 20-one; AP). This steroid produces pharmacological and behavioral effects similar to those elicited by anxiolytic, anticonvulsant, and hypnotic drugs that modulate GABA A receptor-mediated transmission. The anxiolytic and anticon- vulsant properties of progesterone (PROG), its precursor, are probably mostly due to AP. Changes in the central or periph- eral production of PROG and AP have thus been detected 0039-128X/$ – see front matter © 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.steroids.2005.03.014