A combination of polymorphisms in HSD11B1 associates with in vivo 11β-HSD1 activity and metabolic syndrome in women with and without polycystic ovary syndrome

ObjectiveRegeneration of cortisol by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) within liver and adipose tissue may be of pathophysiological importance in obesity and the metabolic syndrome. single nucleotide polymorphisms (SNPs) in HSD11B1, the gene encoding 11β-HSD1, have been associated with type 2 diabetes and hypertension in population-based cohort studies, and with hyperandrogenism in patients with the polycystic ovary syndrome (PCOS). However, the functional consequences of these SNPs for in vivo 11β-HSD1 expression and activity are unknown.MethodsWe explored associations of well-characterised hormonal and metabolic phenotypes with two common SNPs (rs846910 and rs12086634) in HSD11B1 in 600 women (300 with PCOS) and investigated 11β-HSD1 expression and activity in a nested study of 40 women from this cohort.ResultsHSD11B1 genotypes (as single SNPs and as the combination of the two minor allele SNPs) were not associated with PCOS. Women who were heterozygous for rs846910 A and homozygous for rs12086634 T (GA, TT genotype) had a higher risk of metabolic syndrome, regardless of the diagnosis of PCOS (odds ratio in the whole cohort=2.77 (95% confidence interval (CI) 1.16–6.67), P=0.023). In the nested cohort, women with the GA, TT genotype had higher HSD11B1 mRNA levels in adipose tissue, and higher rates of appearance of cortisol and d3-cortisol (16.1±0.7 nmol/min versus 12.1±1.1, P=0.044) during 9,11,12,12-2H4-cortisol (d4-cortisol) steady-state infusion.ConclusionsWe conclude that, in a population of Southern European Caucasian women with and without PCOS, alleles of HSD11B1 containing the two SNPs rs846910 A and rs12086634 T confer increased 11β-HSD1 expression and activity, which associates with the metabolic syndrome.

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The Polycystic Ovary Syndrome and the Metabolic Syndrome: A Possible Chronobiotic-Cytoprotective Adjuvant Therapy

International Journal of Endocrinology ◽

10.1155/2018/1349868 ◽

2018 ◽

Vol 2018 ◽

pp. 1-12 ◽

Cited By ~ 9

Author(s):

Eduardo Spinedi ◽

Daniel P. Cardinali

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Adipose Tissue ◽

Polycystic Ovary Syndrome ◽

White Adipose Tissue ◽

Polycystic Ovary ◽

Ovary Syndrome ◽

The Metabolic Syndrome ◽

Obstructive Sleep ◽

The Impact

Polycystic ovary syndrome is a highly frequent reproductive-endocrine disorder affecting up to 8–10% of women worldwide at reproductive age. Although its etiology is not fully understood, evidence suggests that insulin resistance, with or without compensatory hyperinsulinemia, and hyperandrogenism are very common features of the polycystic ovary syndrome phenotype. Dysfunctional white adipose tissue has been identified as a major contributing factor for insulin resistance in polycystic ovary syndrome. Environmental (e.g., chronodisruption) and genetic/epigenetic factors may also play relevant roles in syndrome development. Overweight and/or obesity are very common in women with polycystic ovary syndrome, thus suggesting that some polycystic ovary syndrome and metabolic syndrome female phenotypes share common characteristics. Sleep disturbances have been reported to double in women with PCOS and obstructive sleep apnea is a common feature in polycystic ovary syndrome patients. Maturation of the luteinizing hormone-releasing hormone secretion pattern in girls in puberty is closely related to changes in the sleep-wake cycle and could have relevance in the pathogenesis of polycystic ovary syndrome. This review article focuses on two main issues in the polycystic ovary syndrome-metabolic syndrome phenotype development: (a) the impact of androgen excess on white adipose tissue function and (b) the possible efficacy of adjuvant melatonin therapy to improve the chronobiologic profile in polycystic ovary syndrome-metabolic syndrome individuals. Genetic variants in melatonin receptor have been linked to increased risk of developing polycystic ovary syndrome, to impairments in insulin secretion, and to increased fasting glucose levels. Melatonin therapy may protect against several metabolic syndrome comorbidities in polycystic ovary syndrome and could be applied from the initial phases of patients’ treatment.

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Abstract #781: Association Between the Polycystic Ovary Syndrome and the Metabolic Syndrome in Women in Puerto Rico

Endocrine Practice ◽

10.1016/s1530-891x(20)43640-7 ◽

2005 ◽

Vol 11 ◽

pp. 66

Author(s):

Marielsa Rabelo ◽

Margarita Ramírez

Keyword(s):

Metabolic Syndrome ◽

Puerto Rico ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Ovary Syndrome ◽

The Metabolic Syndrome

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Prevalence of the metabolic syndrome in women with a previous diagnosis of polycystic ovary syndrome: long-term follow-up

Fertility and Sterility ◽

10.1016/j.fertnstert.2011.08.006 ◽

2011 ◽

Vol 96 (5) ◽

pp. 1271-1274 ◽

Cited By ~ 26

Author(s):

Miriam Hudecova ◽

Jan Holte ◽

Matts Olovsson ◽

Anders Larsson ◽

Christian Berne ◽

...

Keyword(s):

Metabolic Syndrome ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Ovary Syndrome ◽

The Metabolic Syndrome ◽

Previous Diagnosis ◽

Long Term Follow Up

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The prevalence of Gly972Arg and C825T polymorphisms in Slovak women with polycystic ovary syndrome and their relation to the metabolic syndrome

Gynecological Endocrinology ◽

10.3109/09513590903511497 ◽

2010 ◽

Vol 26 (5) ◽

pp. 356-360 ◽

Cited By ~ 9

Author(s):

Ingrid Dravecká ◽

Ivica Lazúrová ◽

Viera Habalová

Keyword(s):

Metabolic Syndrome ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Ovary Syndrome ◽

The Metabolic Syndrome

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Polycystic ovary syndrome: reproductive aspects

Oxford Textbook of Endocrinology and Diabetes ◽

10.1093/med/9780199235292.003.0851 ◽

2011 ◽

pp. 1229-1234

Author(s):

Sophie Catteau-Jonard ◽

Cécile Gallo ◽

Didier Didier

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Reproductive Age ◽

Therapeutic Approaches ◽

Women Of Reproductive Age ◽

Ovary Syndrome ◽

Common Cause ◽

The Metabolic Syndrome

The polycystic ovary syndrome (PCOS) is the most common cause of anovulation and hyperandrogenism in women, affecting between 5 and 10% of women of reproductive age worldwide (1). Although this difficult topic in endocrine gynaecology is under extensive research, controversies still remain about the pathophysiology, diagnosis, and therapy of PCOS. The PCOS phenotype can be structured in three components: manifestations of anovulation, hyperandrogenism, and the metabolic syndrome (of which hyperinsulinaemia secondary to insulin resistance is the central abnormality). The latter two are addressed in other chapters. Our knowledge about the mechanism of disturbed folliculogenesis in PCOS that is responsible for its reproductive aspects has much increased these last years, thus opening new avenues for the diagnostic and therapeutic approaches.

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