Steroids and the metabolic syndrome

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Abdominal obesity, insulin resistance and the metabolic syndrome

Over the last 15 years, the concept underlying the common aggregation of major abnormalities associated with an insulin resistant state has emerged as a unique entity, the so-called metabolic syndrome. Although the concept that insulin resistance is different from the metabolic syndrome, nonetheless for many years these two conditions have often been used more or less as synonyms. This issue is, however, currently a matter of great controversy [1]. One of the reasons is certainly represented by

Pathophysiological aspects of abdominal obesity: the hypothalamic–pituitary–adrenal axis and sex hormone imbalance

Steroids play an important role in the regulation of adipose tissue metabolism, with relevant differences according to its distribution [7], [8], [9], [10]. Alterations of the hypothalamic–pituitary–adrenal (HPA) axis and sex hormone imbalance may have profound effects on adipose tissue morphology and function. In the following sections multiple alterations of these two classic endocrine compartments in the presence of central obesity are discussed.

Visceral obesity as a part of the “general maladaptation syndrome”

Life exists by maintaining a complex dynamic equilibrium or homeostasis that is constantly challenged by intrinsic and extrinsic adverse forces, the stressors. When faced with excessive stress, whether physical or emotional, a subject's adaptive responses acquire a relatively stereotypic nonspecific nature, referred to by Selye as “the general adaptation syndrome” [34]. Stress activates the HPA axis and sympathetic nervous and the sympathoadrenal systems [35]. Defence reactions involve release

Association between steroid imbalance, insulin resistance and the metabolic syndrome

What is reported in the previous paragraphs emphasises the fact that alterations of the glucocorticoid axis combined with a sex hormone imbalance may have a coordinating role in the pathophysiology of central obesity and associated metabolic alterations. In the following part of this review, we will focus on the studies showing an association between abnormalities of the HPA axis and those of sex hormones, particularly androgens, with the metabolic syndrome, T2DM and CVDs.

Summary and conclusions

The concept that central obesity and associated metabolic and cardiovascular co-morbidities may be part of the so-called “general adaptation syndrome” proposed by Salye 60 years ago has attracted scientific attention in the last 15 years, although the pathophysiology of this relationship in humans is poorly understood. However, animal data support this concept and emphasize the role of the two main stress endocrine systems, the HPA axis and the SNS, in the cascade on events leading to end

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References (97)

  • G. Hergenc et al.

    Associations of obesity markers, insulin, and sex hormones with HDL-cholesterol levels in Turkish and German individuals

    Atherosclerosis

    (1999)
  • R. Pasquali et al.

    Role of changes in dietary habits in polycystic ovary syndrome

    Reprod. Biomed. Online

    (2004)
  • R. Kahn et al.

    The metabolic syndrome: time for a critical rappraisal. Joint statement from the American Diabetes Association and the European Association for the study of Diabetes

    Diabetes Care

    (2005)
  • G.M. Reaven

    Insulin resistance in human disease

    Diabetes

    (1988)
  • Executive summary of the Third Report of The National Cholesterol Education Program (NCEP) expert panel on detection,...
  • International Diabetes Federation: the IDF worldwide definition of the metabolic syndrome, available from...
  • K.L. Cheal et al.

    Relationship to insulin resistance of the adult treatment panel III diagnostic criteria for identification of the metabolic syndrome

    Diabetes

    (2004)
  • M.S. Greenfield et al.

    Assessment of insulin resistance with insulin suppression test and the euglycemic clamp

    Diabetes

    (1981)
  • B.L. Wajchenberg

    Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome

    Endocr. Rev.

    (2000)
  • R. Pasquali et al.

    Obesity and hormonal abnormalities

  • P. Bjorntorp

    The regulation of adipose tissue distribution in humans

    Int. J. Obes.

    (1996)
  • R. Pasquali et al.

    The abdominal obesity phenotype and insulin resistance are associated with abnormalities of the hypothalamic–pituitary–adrenal axis in humans

    Horm. Metab. Res.

    (2000)
  • P. Bjorntorp et al.

    Neuroendocrine abnormalities in visceral obesity

    Int. J. Obes.

    (2000)
  • R. Pasquali et al.

    The hypothalamic–pituitary–adrenal axis activity in obesity and the metabolic syndrome

    Ann. NY Acad. Sci.

    (2006)
  • M. Rebuffé-Scrive et al.

    Glucocorticoid hormone binding to human adipose tissue

    Eur. J. Clin. Invest.

    (1985)
  • J.W. Tomlinson et al.

    11ß-Hydroxysteroid dehydrogenase type 1: a tissue specific regulation of glucorticoid response

    Endocr. Rev.

    (2004)
  • H. Masuzaki et al.

    A transgenic model of visceral obesity and the metabolic syndrome

    Science

    (2001)
  • Y. Kotelevtsev et al.

    11b-Hydroxysteroid dehydrogenase type 1 knockout mice show attenuated glucocorticoid-inducible responses and resist hyperglycemia on obesity or stress

    Proc. Natl. Acad. Sci.

    (1997)
  • B. Von Shoultz et al.

    On the regulation of sex-hormone-binding globulin. A challenge of old dogma and outlines of an alternative mechanism

    J. Steroid Biochem.

    (1989)
  • A. Tchernof et al.

    Sex steroid hormones, sex hormone-binding globulin, and obesity in men and women

    Horm. Metab. Res.

    (2000)
  • E. Samojlik et al.

    Elevated production and metabolic clearance rates of androgens in morbidly obese women

    J. Clin. Endocrinol. Metab.

    (1984)
  • M.A. Kirschner et al.

    Androgen–estrogen metabolism in women with upper body versus lower body obesity

    J. Clin. Endocrinol. Metab.

    (1990)
  • B.R. Kurtz et al.

    Maintenance of normal circulating levels of Δ4-androstenedine and dehydroepiandrosterone in simple obesity despite increased metabolic clearance rates: evidence for a servo-control mechanism

    J. Clin. Endocrinol. Metab.

    (1987)
  • R. Pasquali et al.

    Characterization of obese women with reduced sex hormone-binding globulin concentrations

    Horm. Metab. Res.

    (1990)
  • D.J. Evans et al.

    Relationship of androgenic activity to body fat topography, fat cell morphology and metabolic aberrations in premenopausal women

    J. Clin. Endocrinol. Metab.

    (1983)
  • B. Zumoff et al.

    Plasma free and non-sex-hormone-binding-globulin-bound testosterone are decreased in obese men in proportion to their degree of obesity

    J. Clin. Endocrinol. Metab.

    (1990)
  • V.A. Giagulli et al.

    Origin and significance of plasma androsterone glucuronide levels: a parameter of adrenal androgen secretion and hepatic 5 alpha-reductase activity

    J. Clin. Endocrinol. Metab.

    (1993)
  • R. Leenen et al.

    Visceral fat accumulation in relation to sex hormones in obese men and women undergoing weight loss therapy

    J. Clin. Endocrinol. Metab.

    (1994)
  • H. Selye

    Syndrome produced by diverse nocuous agents

    Nature

    (1936)
  • P.M. Plotsky et al.

    Catecholaminergic modulation of corticotropin-releasing factor and adrenocorticotropin secretion

    Endocr. Rev.

    (1989)
  • P. Hjemdahl

    Stress and the metabolic syndrome. An interesting but enigmating association

    Circulation

    (2002)
  • B.S. McEwen

    Protective and damaging effects of stress mediators

    N. Engl. J. Med.

    (1998)
  • C. Shively et al.

    Regional obesity and coronary atherosclerosis in females: a non-human primate model

    Acta Med. Scand.

    (1989)
  • P. Bjorntorp

    Centralization of body fat

  • G.P. Chrousos

    Editorial: a healthy body in a healthy mind and vice versa. The damaging power of “uncontrollable” stress

    J. Clin. Endocrinol. Metab.

    (1998)
  • P. Björntorp

    Visceral obesity: a “Civilization Syndrome”

    Obes. Res.

    (1993)
  • R. Rosmond et al.

    The influence of occupational and social factors on obesity and body fat distribution in middle aged-men

    Int. J. Obes.

    (1996)
  • R. Rosmond et al.

    Mental distress, obesity and body fat distribution in middle-aged women

    Obes. Res.

    (1996)
  • Cited by (11)

    View all citing articles on Scopus

    Presented at the ‘12th International Congress on Hormonal Steroids and Hormones & Cancer’ (Athens, Greece, 13–16 September 2006).

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