Polycystic ovary syndrome: insight into pathogenesis and a common association with insulin resistance

Barber, Thomas M.; Dimitriadis, Georgios K.; Andreou, Avgi; Franks, Stephen

doi:10.7861/clinmedicine.15-6-s72

Cited by 81 publications

(55 citation statements)

References 32 publications

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“…Although the etiology of PCOS is undefined and likely to be multivariate (14,15), exposure to elevated androgens in early development is known to trigger reproductive and metabolic traits of PCOS during adult life in both humans (16,17) and in a variety of animal models (18)(19)(20). Notably, daughters of PCOS Androgen excess is a hallmark of polycystic ovary syndrome (PCOS), a prevalent yet poorly understood endocrine disorder.…”

Section: Introductionmentioning

confidence: 99%

Ontogeny and reversal of brain circuit abnormalities in a preclinical model of PCOS

Silva¹,

Prescott²,

Campbell³

2018

JCI Insight

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Androgen excess is a hallmark of polycystic ovary syndrome (PCOS), a prevalent yet poorly understood endocrine disorder. Evidence from women and preclinical animal models suggests that elevated perinatal androgens can elicit PCOS onset in adulthood, implying androgen actions in both PCOS ontogeny and adult pathophysiology. Prenatally androgenized (PNA) mice exhibit a robust increase of progesterone-sensitive GABAergic inputs to gonadotropin-releasing hormone (GnRH) neurons implicated in the pathogenesis of PCOS. It is unclear when altered GABAergic wiring develops in the brain, and whether these central abnormalities are dependent upon adult androgen excess. Using GnRH-GFP-transgenic mice, we determined that increased GABA input to GnRH neurons occurs prior to androgen excess and the manifestation of reproductive impairments in PNA mice. These data suggest that brain circuit abnormalities precede the postpubertal development of PCOS traits. Despite the apparent developmental programming of circuit abnormalities, long-term blockade of androgen receptor signaling from early adulthood rescued normal GABAergic wiring onto GnRH neurons, improved ovarian morphology, and restored reproductive cycles in PNA mice. Therefore, androgen excess maintains changes in female brain wiring linked to PCOS features and the blockade of androgen receptor signaling reverses both the central and peripheral PNA-induced PCOS phenotype.

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Section: Introductionmentioning

confidence: 99%

Ontogeny and reversal of brain circuit abnormalities in a preclinical model of PCOS

Silva¹,

Prescott²,

Campbell³

2018

JCI Insight

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“…Su potencial terapéutico se planea como una "panacea metabólica" antiglicémica, antilipémica e inductora de la pérdida de peso, sin embargo se necesita mucha investigación antes de que las terapias relacionadas con el TAM estén disponibles. 20…”

Section: Iii3 Tratamiento Enfocado a Síndrome Metabólicounclassified

Síndrome de ovario poliquístico

Rodríguez

2019

FMC - Formación Médica Continuada en Atención Primaria

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El síndrome de ovario poliquístico es el trastorno endocrinológico más común en mijeres en edad reproductiva, y se caracteriza por la presencia de hiperandrogenismo con oligo/anovulación, pudiendo estar presente el cambio morfológico en el ovario. En el presente artículo se discuten las clasificaciones actuales, así como las bases fisiopatológicas de la enfermedad y su tratamiento médico y general, en especial relación a la presencia de síndrome metabólico como factor de riesgo de eventos cardio/cerebro vasculares. Rev Med Clin 2018;2(2)75-86. Palabras clave: Síndrome de ovario poliquístico, síndrome metabólico, hiperandrogenismo, anovulación

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“…PCOS is characterized by high luteinizing hormone levels, polycystic ovarian morphology, hyperandrogenism, hyperinsulinemia, and insulin resistance. Excessive androgen production by the ovaries is the main feature of PCOS (1,2). The prevalence of PCOS has increased during the past decade, and its adverse effects on the health of women are becoming more serious (3,4).…”

Section: Introductionmentioning

confidence: 99%

“…Presently, the pathogenesis of PCOS is not fully understood, and requires further investigation. More than 50% of PCOS patients are insulin resistant (2,8), which can partly explain their increased risk for diabetes and cardiovascular disease. Furthermore, insulin resistance can also be the cause for hyperlipidemia and hyperinsulinemia in PCOS patients.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-33b-5p is overexpressed and inhibits GLUT4 by targeting HMGA2 in polycystic ovarian syndrome: An in vivo and in vitro study

Yang

Jiang

Xiao³

et al. 2018

Oncol Rep

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Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disease, but its pathogenesis remains largely unknown. The present study explored the role of microRNA‑33b‑5p (miR‑33b‑5p) in PCOS pathogenesis, with a particular focus on its role in regulating glucose transporter 4 (GLUT4). A rat model of PCOS was developed by injecting female SD rats with insulin and HCG. miR‑33b‑5p, GLUT4, sterol regulatory element‑binding protein 1 (SREBF1), and high mobility group A2 (HMGA2) expression in rat ovarian tissues was examined by qRT‑PCR and immunohistochemistry. The effect of a high dose of either glucose or insulin on miR‑33b‑5p, GLUT4, SREBF1 and HMGA2 expression was also examined in cultured adipocytes by qRT‑PCR and western blotting. Additionally, the luciferase reporter assay and chromatin immunoprecipitation (ChIP) were used to explore the role of miR‑33b‑5p in regulating HMGA2, SREBF‑1 and/or GLUT4. Elevated levels of miR‑33b‑5p expression were detected in the ovarian tissues of insulin resistant PCOS rats, and those levels were negatively correlated with those of GLUT4, HMGA2 and SREBF1 expression (P<0.05). Immunohistochemistry studies revealed that GLUT4, SREBF1, and HMGA2 expression levels in the ovarian tissues of insulin resistant PCOS rats were significantly lower than those in other groups of rats. In cultured adipocytes, excess extracellular glucose or insulin increased miR‑33b‑5p expression but reduced GLUT4, SREBF1 and HMGA2 expression, whereas the levels of GLUT4, SREBF1 and HMGA2 were elevated by inhibition of miR‑33b‑5. HMGA2 could directly bind to the 5'‑promoter region of GLUT4 and promote its expression, and could also promote SREBF1 expression. Moreover, SREBF1 could also directly bind to the 5'‑promoter region of GLUT4 and promote its expression. Our findings revealed that miR‑33b‑5p was overexpressed in the ovarian tissues of insulin resistant PCOS rats, and thus may play an important role in the development of insulin resistance in PCOS patients. miR‑33b‑5p can inhibit GLUT4 production by targeting HMGA2, and in addition, HMGA2 and SREBF1 are important molecules involved in modulating GLUT4 expression.

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Polycystic ovary syndrome: insight into pathogenesis and a common association with insulin resistance

Cited by 81 publications

References 32 publications

Ontogeny and reversal of brain circuit abnormalities in a preclinical model of PCOS

Ontogeny and reversal of brain circuit abnormalities in a preclinical model of PCOS

Síndrome de ovario poliquístico

MicroRNA-33b-5p is overexpressed and inhibits GLUT4 by targeting HMGA2 in polycystic ovarian syndrome: An in vivo and in vitro study

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