Altered Ovarian Inositol Ratios May Account for Pathological Steroidogenesis in PCOS

Unfer, Vittorio; Dinicola, Simona; Laganà, Antonio Simone; Bizzarri, Mariano

doi:10.3390/ijms21197157

Cited by 38 publications

(26 citation statements)

References 57 publications

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“…In this regard, higher myo-Ins/D-chiro-Ins ratios should increase aromatase activity in granulosa, fostering estrogen biosynthesis, while lower myo-Ins/D-chiro-Ins ratios promote androgen production in thecal cells [ 131 ].…”

Section: Emerging Roles For Inositol Treatmentsmentioning

confidence: 99%

Inositols: From Established Knowledge to Novel Approaches

Dinicola¹,

Unfer²,

Facchinetti

et al. 2021

IJMS

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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.

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Section: Emerging Roles For Inositol Treatmentsmentioning

confidence: 99%

Inositols: From Established Knowledge to Novel Approaches

Dinicola¹,

Unfer²,

Facchinetti

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

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“…The epimerase, which is responsible for the conversion of MI to DCI, has a tissue-specific activity [ 68 ] and has the key role for the MI:DCI specific ratios in different tissues and organs [ 69 ]. In this regard, Figure 1 shows the action of epimerase on MI to DCI conversion and its relationship with aromatase [ 70 ].…”

Section: Discussionmentioning

confidence: 99%

Fertility-Sparing Approach in Women Affected by Stage I and Low-Grade Endometrial Carcinoma: An Updated Overview

Gullo

Etrusco

Cucinella

et al. 2021

IJMS

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Endometrial cancer (EC) is a deleterious condition which strongly affects a woman’s quality of life. Although aggressive interventions should be considered to treat high-grade EC, a conservative approach should be taken into consideration for women wishing to conceive. In this scenario, we present an overview about the EC fertility-sparing approach state of art. Type I EC at low stage is the only histological type which can be addressed with a fertility-sparing approach. Moreover, no myometrium and/or adnexal invasion should be seen, and lymph-vascular space should not be involved. Regarding the pharmaceutical target, progestins, in particular medroxyprogesterone acetate (MPA) or megestrol acetate (MA), are the most employed agent in conservative treatment of early-stage EC. The metformin usage and hysteroscopic assessment is still under debate, despite promising results. Particularly strict and imperious attention should be given to the follow-up and psychological wellbeing of women, especially because of the double detrimental impairment: both EC and EC-related infertility consequences.

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“…When PCOS is relieved, the ovarian function will be restored to its original function. The ovaries can well control the body's male hormones under normal physiological functions (68,69). Secretion, which solves the urgent need of people with PCOS, and also points out the direction for the next in-depth study of DCI.…”

Section: Effect Of D-chiro Inositol On the Expression Of Genes Related To Insulin Resistance Pathwaymentioning

confidence: 93%

Differential Gene Expression and Biological Analyses of Primary Hepatocytes Following D-Chiro-Inositol Supplement

et al. 2021

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Dietary supplements have improved the prevention of insulin resistance and metabolic diseases, which became a research hotspot in food science and nutrition. Obesity and insulin resistance, caused by a high-fat diet, eventually result in severe metabolic diseases, can be prevented with the dietary supplement D-chiro-inositol (DCI). In this work, we isolated mice primary hepatocytes with palmitic acid stimulation and DCI was applied to compare and contrast its effects of in primary hepatocyte biology. Before and after intervention with DCI, we used RNA-Seq technology to establish a primary hepatocyte transcriptome gene profile. We found that both PA and DCI cause a wide variation in gene expression. Particularly, we found that DCI plays critical role in this model by acting on glycolysis and gluconeogenesis. Overall, we generated extensive transcripts from primary hepatocytes and uncovered new functions and gene targets for DCI.

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Altered Ovarian Inositol Ratios May Account for Pathological Steroidogenesis in PCOS

Cited by 38 publications

References 57 publications

Inositols: From Established Knowledge to Novel Approaches

Inositols: From Established Knowledge to Novel Approaches

Fertility-Sparing Approach in Women Affected by Stage I and Low-Grade Endometrial Carcinoma: An Updated Overview

Differential Gene Expression and Biological Analyses of Primary Hepatocytes Following D-Chiro-Inositol Supplement

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