Ali Cenk Ozay, Vittorio Unfer, Cherubino Di Lorenzo, Olga Papalou, Daniele Barbaro, Salvatore Benvenga, Mónica H. Vazquez-Levin, Pietro Cavalli, Arturo Bevilacqua, Nicholas D. E. Greene, Scott Roseff, Marialuisa Appetecchia, Rosario D'Anna, Maurizio Nordio, John E. Nestler, Cesare Aragona, Andrew J. Copp, Eleni Kandaraki, Mariano Bizzarri, Maria Salome Bezerra Espinola, Didier Dewailly, Fabio Facchinetti, Giovanni Monastra, Lali Pkhaladze, Ivana Vucenik, Simona Dinicola, Shiao-Yng Chan, Artur Wdowiak, Imelda Hernández Marín, Christophe O. Soulage, Evanthia Diamanti-Kandarakis, Moshe Hod, Antonio Simone Laganà, Annarita Stringaro, Nikos Prapas, Tony T. Y. Chiu, Tonino Cantelmi, Mario Montanino Oliva, Giuseppina Porcaro, Zdravko Kamenov, Systems Biology Group Lab [Rome, Italy] (SBGL), University - Hospital of Modena and Reggio Emilia [Modena, Italy], Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University College of London [London] (UCL), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Universitá degli Studi dell’Insubria = University of Insubria [Varese] (Uninsubria), National University of Singapore (NUS), Zhordania and Khomasuridze Institute of Reproductology [Tbilisi, Georgia] (ZKIR), University of Messina, National Center for Drug Research and Evaluation [Rome, Italy], Istituto Superiore di Sanità (ISS), Azienda Usl Toscana nord ovest [Livorno, Italy] (AUTNO), Regina Elena National Cancer Institute [Rome], Institute for Interpersonal Cognitive Therapy [Rome, Italy] (2ICT), Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), The Chinese University of Hong Kong [Hong Kong], Université de Lille, Hygeia Hospital [Athens, Greece] (2H), Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM), Tel Aviv University (TAU), Medical University of Sofia [Bulgarie], Santo Spirito Hospital [Athens, Greece] (2SH), Virginia Commonwealth University (VCU), Azienda Sanitaria Locale [ROMA] (ASL), Near East University, USL UMBRIA [Terni, Italy] (USLU), IAKENTRO [Thessaloniki, Greece], South Florida Institute for Reproductive Medicine [Boca Raton, FL, USA] (IVFMD), Instituto de Biología y Medicina Experimental [Buenos Aires] (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET), University of Maryland [Baltimore], Medical University of Lublin, Istituto Superiore di Sanita [Rome], and CarMeN, laboratoire
International audience; Myo-inositol (myo-Ins) and D-chiro-inositol (D-chiro-Ins) are natural compounds involved in many biological pathways. Since the discovery of their involvement in endocrine signal transduction, myo-Ins and D-chiro-Ins supplementation has contributed to clinical approaches in ameliorating many gynecological and endocrinological diseases. Currently both myo-Ins and D-chiro-Ins are well-tolerated, effective alternative candidates to the classical insulin sensitizers, and are useful treatments in preventing and treating metabolic and reproductive disorders such as polycystic ovary syndrome (PCOS), gestational diabetes mellitus (GDM), and male fertility disturbances, like sperm abnormalities. Moreover, besides metabolic activity, myo-Ins and D-chiro-Ins deeply influence steroidogenesis, regulating the pools of androgens and estrogens, likely in opposite ways. Given the complexity of inositol-related mechanisms of action, many of their beneficial effects are still under scrutiny. Therefore, continuing research aims to discover new emerging roles and mechanisms that can allow clinicians to tailor inositol therapy and to use it in other medical areas, hitherto unexplored. The present paper outlines the established evidence on inositols and updates on recent research, namely concerning D-chiro-Ins involvement into steroidogenesis. In particular, D-chiro-Ins mediates insulin-induced testosterone biosynthesis from ovarian thecal cells and directly affects synthesis of estrogens by modulating the expression of the aromatase enzyme. Ovaries, as well as other organs and tissues, are characterized by a specific ratio of myo-Ins to D-chiro-Ins, which ensures their healthy state and proper functionality. Altered inositol ratios may account for pathological conditions, causing an imbalance in sex hormones. Such situations usually occur in association with medical conditions, such as PCOS, or as a consequence of some pharmacological treatments. Based on the physiological role of inositols and the pathological implications of altered myo-Ins to D-chiro-Ins ratios, inositol therapy may be designed with two different aims: (1) restoring the inositol physiological ratio; (2) altering the ratio in a controlled way to achieve specific effects.