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ORIGINAL RESEARCH—BASIC SCIENCE: Sexually Dimorphic Effects of Testosterone Administration on Brain Allopregnanolone in Gonadectomized Rats

Authors

  • Nicola Pluchino MD,

    1. Department of Reproductive Medicine and Child Development, Division of Gynecology and Obstetrics and University Centre for Adaptive Disorders and Headache, University of Pisa, Pisa, Italy;
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  • Filippo Ninni MD,

    1. Department of Reproductive Medicine and Child Development, Division of Gynecology and Obstetrics and University Centre for Adaptive Disorders and Headache, University of Pisa, Pisa, Italy;
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  • Elena Casarosa MD, PhD,

    1. Department of Reproductive Medicine and Child Development, Division of Gynecology and Obstetrics and University Centre for Adaptive Disorders and Headache, University of Pisa, Pisa, Italy;
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  • Elena Lenzi MD,

    1. Department of Reproductive Medicine and Child Development, Division of Gynecology and Obstetrics and University Centre for Adaptive Disorders and Headache, University of Pisa, Pisa, Italy;
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  • Silvia Begliuomini MD,

    1. Department of Reproductive Medicine and Child Development, Division of Gynecology and Obstetrics and University Centre for Adaptive Disorders and Headache, University of Pisa, Pisa, Italy;
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  • Vito Cela MD, PhD,

    1. Department of Reproductive Medicine and Child Development, Division of Gynecology and Obstetrics and University Centre for Adaptive Disorders and Headache, University of Pisa, Pisa, Italy;
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  • Stefano Luisi MD, PhD,

    1. Division of Obstetrics and Gynecology, University of Siena, Siena, Italy
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  • Letizia Freschi MD,

    1. Department of Reproductive Medicine and Child Development, Division of Gynecology and Obstetrics and University Centre for Adaptive Disorders and Headache, University of Pisa, Pisa, Italy;
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  • Sara Merlini MD,

    1. Department of Reproductive Medicine and Child Development, Division of Gynecology and Obstetrics and University Centre for Adaptive Disorders and Headache, University of Pisa, Pisa, Italy;
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  • Andrea Giannini MD,

    1. Department of Reproductive Medicine and Child Development, Division of Gynecology and Obstetrics and University Centre for Adaptive Disorders and Headache, University of Pisa, Pisa, Italy;
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  • Alessandra Cubeddu MD,

    1. Department of Reproductive Medicine and Child Development, Division of Gynecology and Obstetrics and University Centre for Adaptive Disorders and Headache, University of Pisa, Pisa, Italy;
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  • Andrea Riccardo Genazzani MD, PhD, FRCOG

    1. Department of Reproductive Medicine and Child Development, Division of Gynecology and Obstetrics and University Centre for Adaptive Disorders and Headache, University of Pisa, Pisa, Italy;
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Nicola Pluchino, MD and AR Genazzani, MD, PhD, FRCOG, Department of Reproductive Medicine and Child Development, Division of Gynecology and Obstetrics, University of Pisa, Via Roma 35, 56100 Pisa, Italy. Tel: 39-50-503985; Fax: 39-50-553410; E-mail: nicola.pluchino@med.unipi.it

ABSTRACT

Introduction.  Clinical and biological evidences have shown a wide range of neuroactive effects of testosterone administration.

Aim.  Evaluation of the effects of 2-weeks treatment with testosterone (T), Dihydrotestosterone (DHT), and estradiol valerate (E2V) on brain and serum allopregnanolone (AP) in gonadectomized rats of both sexes.

Main Outcome Measures.  AP levels were measured in frontal and parietal lobe, hippocampus, hypothalamus, anterior pituitary, and in serum.

Methods.  Eight groups of Wistar female and eight groups of Wistar male rats were included. For each sex, one group of fertile and one group of gonadectomized rats were employed as control receiving placebo. The others groups received subcutaneous T at the dose of 10 µg/kg/day and 100 µg/kg/day for female rats, and 1 mg/kg/day and 5 mg/kg/day for male rats, or DHT at the doses of 1 µg/kg/day, 10 µg/kg/day, and 100 µg/kg/day for females, and 0, 1 µg/kg/day, 1 mg/kg/day and 5 mg/kg/day for males, or E2V (0.05 mg/Kg/day).

Results:  Ovariectomy (OVX) and orchidectomy (OCX) induced a significant decrease in AP in all brain areas analyzed, as well as in serum. In OVX rats, T replacement, as well as E2V, significantly increased AP content in all brain areas and in plasma. In OCX, T and E2V did not actively result in influencing AP concentration in frontal and parietal lobe, while it produced a significant rise in AP levels in the hippocampus, hypothalamus, anterior pituitary, and serum. Conversely, DHT replacement had no affect on AP levels anywhere or at any administered dose, either in males or in female rats.

Conclusions.  Gender difference and T therapy affect brain AP synthesis/release during the reproductive aging. This effect becomes particularly evident in the brain of ovariectomized animals, where the content of this specific neurosteroid is much more responsive than male animals to testosterone replacement. Pluchino N, Ninni F, Casarosa E, Lenzi E, Begliuomini S, Cela V, Luisi S, Freschi L, Merlini S, Giannini A, Cubeddu A, and Genazzani AR. Sexually dimorphic effects of testosterone administration on brain allopregnanolone in gonadectomized rats. J Sex Med 2008;5:2780–2792.

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