Abstract
Objective:
To investigate the expression of 11β-hydroxysteroid dehydrogenase (11β-HSD) type 1 and 2 and hexose-6-phosphate dehydrogenase (H6PDH) mRNA in subcutaneous abdominal tissue from lean and obese women with and without polycystic ovary syndrome (PCOS), and to investigate the association between these enzymes and different measures of insulin sensitivity.
Design:
Cross-sectional study.
Subjects:
A total of 60 women, 36 women with PCOS, 17 lean (lean PCOS, LP) and 19 obese (obese PCOS, OP) and 24 age- and weight-matched control women, 8 lean (lean controls, LC) and 16 obese (obese controls, OC). Subcutaneous adipose tissue was collected from the abdomen. Peripheral insulin sensitivity was assessed by the euglycemic hyperinsulinemic clamp and determined as glucose disposal rate and insulin sensitivity index. Whole-body insulin sensitivity was calculated using homeostasis model assessment insulin resistance index. Body composition was evaluated by dual X-ray absorptiometry. Adipose mRNA expression of leptin and adiponectin were determined by real-time PCR.
Results:
Polycystic ovary syndrome (P<0.05) and obesity (P<0.05) were independently associated with increased expression of 11β-HSD1 mRNA. The subgroups LP and OC had increased 11β-HSD1 and 11β-HSD2 mRNA expression compared with LC (P<0.05, P<0.05). There were no effects of PCOS or obesity on11β-HSD2 or H6PDH mRNA expression. Decreased peripheral insulin sensitivity (P<0.001) and increased upper body fat distribution (P<0.01) were associated with increased expression of 11β-HSD1, but neither 11β-HSD2 nor H6PDH.
Conclusion:
Polycystic ovary syndrome and obesity are independently associated with increased expression of 11β-HSD1. This may lead to increased conversion of cortisone to cortisol in the peripheral adipose tissue and subsequently increased glucocorticoid activity. Decreased peripheral insulin sensitivity and central obesity was associated with increased expression of 11β-HSD1.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Friedman TC, Mastorakos G, Newman TD, Mullen NM, Horton EG, Costello R et al. Carbohydrate and lipid metabolism in endogenous hypercortisolism: shared features with metabolic syndrome X and NIDDM. Endocr J 1996; 43: 645–655.
Krakoff LR . Glucocorticoid excess syndromes causing hypertension. Cardiol Clin 1988; 6: 537–545.
Nosadini R, Del PS, Tiengo A, Valerio A, Muggeo M, Opocher G et al. Insulin resistance in Cushing's syndrome. J Clin Endocrinol Metab 1983; 57: 529–536.
Stewart PM, Boulton A, Kumar S, Clark PM, Shackleton CH . Cortisol metabolism in human obesity: impaired cortisone → cortisol conversion in subjects with central adiposity. J Clin Endocrinol Metab 1999; 84: 1022–1027.
Andrews RC, Herlihy O, Livingstone DE, Andrew R, Walker BR . Abnormal cortisol metabolism and tissue sensitivity to cortisol in patients with glucose intolerance. J Clin Endocrinol Metab 2002; 87: 5587–5593.
Rask E, Walker BR, Soderberg S, Livingstone DE, Eliasson M, Johnson O et al. Tissue-specific changes in peripheral cortisol metabolism in obese women: increased adipose 11beta-hydroxysteroid dehydrogenase type 1 activity. J Clin Endocrinol Metab 2002; 87: 3330–3336.
Masuzaki H, Paterson J, Shinyama H, Morton NM, Mullins JJ, Seckl JR et al. A transgenic model of visceral obesity and the metabolic syndrome. Science 2001; 294: 2166–2170.
Morton NM, Holmes MC, Fievet C, Staels B, Tailleux A, Mullins JJ et al. Improved lipid and lipoprotein profile, hepatic insulin sensitivity, and glucose tolerance in 11beta-hydroxysteroid dehydrogenase type 1 null mice. J Biol Chem 2001; 276: 41293–41300.
Rask E, Olsson T, Soderberg S, Andrew R, Livingstone DE, Johnson O et al. Tissue-specific dysregulation of cortisol metabolism in human obesity. J Clin Endocrinol Metab 2001; 86: 1418–1421.
Lindsay RS, Wake DJ, Nair S, Bunt J, Livingstone DE, Permana PA et al. Subcutaneous adipose 11 beta-hydroxysteroid dehydrogenase type 1 activity and messenger ribonucleic acid levels are associated with adiposity and insulinemia in Pima Indians and Caucasians. J Clin Endocrinol Metab 2003; 88: 2738–2744.
Kannisto K, Pietilainen KH, Ehrenborg E, Rissanen A, Kaprio J, Hamsten A et al. Overexpression of 11beta-hydroxysteroid dehydrogenase-1 in adipose tissue is associated with acquired obesity and features of insulin resistance: studies in young adult monozygotic twins. J Clin Endocrinol Metab 2004; 89: 4414–4421.
Walker BR, Connacher AA, Lindsay RM, Webb DJ, Edwards CR . Carbenoxolone increases hepatic insulin sensitivity in man: a novel role for 11-oxosteroid reductase in enhancing glucocorticoid receptor activation. J Clin Endocrinol Metab 1995; 80: 3155–3159.
Bublitz C, Steavenson S . The pentose phosphate pathway in the endoplasmic reticulum. J Biol Chem 1988; 263: 12849–12853.
Bujalska IJ, Draper N, Michailidou Z, Tomlinson JW, White PC, Chapman KE et al. Hexose-6-phosphate dehydrogenase confers oxo-reductase activity upon 11 beta-hydroxysteroid dehydrogenase type 1. J Mol Endocrinol 2005; 34: 675–684.
Edwards CR, Stewart PM, Burt D, Brett L, McIntyre MA, Sutanto WS et al. Localisation of 11 beta-hydroxysteroid dehydrogenase--tissue specific protector of the mineralocorticoid receptor. Lancet 1988; 2: 986–989.
Milagro FI, Campion J, Martinez JA . 11-Beta hydroxysteroid dehydrogenase type 2 expression in white adipose tissue is strongly correlated with adiposity. J Steroid Biochem Mol Biol 2007; 104: 81–84.
Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W et al. The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril 2009; 91: 456–488.
The Rotterdam ESHRE/ASRM-sponsored PCOS consensus worshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 2004; 81: 19–25.
Gambineri A, Vicennati V, Genghini S, Tomassoni F, Pagotto U, Pasquali R et al. Genetic variation in 11beta-hydroxysteroid dehydrogenase type 1 predicts adrenal hyperandrogenism among lean women with polycystic ovary syndrome. J Clin Endocrinol Metab 2006; 91: 2295–2302.
Low SC, Assaad SN, Rajan V, Chapman KE, Edwards CR, Seckl JR . Regulation of 11 beta-hydroxysteroid dehydrogenase by sex steroids in vivo: further evidence for the existence of a second dehydrogenase in rat kidney. J Endocrinol 1993; 139: 27–35.
Paulsen SK, Pedersen SB, Fisker S, Richelsen B . 11Beta-HSD type 1 expression in human adipose tissue: impact of gender, obesity, and fat localization. Obesity (Silver Spring) 2007; 15: 1954–1960.
Ferriman D, Gallwey JD . Clinical assessment of body hair growth in women. J Clin Endocrinol Metab 1961; 21: 1440–1447.
Svendsen PF, Nilas L, Norgaard K, Jensen JE, Madsbad S . Obesity, body composition and metabolic disturbances in polycystic ovary syndrome. Hum Reprod 2008; 23: 2113–2121.
Vermeulen A, Verdonck L, Kaufman JM . A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 1999; 84: 3666–3672.
Stewart PM, Shackleton CH, Beastall GH, Edwards CR . 5 alpha-reductase activity in polycystic ovary syndrome. Lancet 1990; 335: 431–433.
Tsilchorozidou T, Honour JW, Conway GS . Altered cortisol metabolism in polycystic ovary syndrome: insulin enhances 5alpha-reduction but not the elevated adrenal steroid production rates. J Clin Endocrinol Metab 2003; 88: 5907–5913.
Fassnacht M, Schlenz N, Schneider SB, Wudy SA, Allolio B, Arlt W . Beyond adrenal and ovarian androgen generation: Increased peripheral 5 alpha-reductase activity in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2003; 88: 2760–2766.
Chin D, Shackleton C, Prasad VK, Kohn B, David R, Imperato-McGinley J et al. Increased 5alpha-reductase and normal 11beta-hydroxysteroid dehydrogenase metabolism of C19 and C21 steroids in a young population with polycystic ovarian syndrome. J Pediatr Endocrinol Metab 2000; 13: 253–259.
Gallagher TF, Kappas A, Hellman L, Lipsett MB, Pearson OH, West CD . Adrenocortical hyperfunction in idiopathic hirsutism and the Stein-Leventhal syndrome. J Clin Invest 1958; 37: 794–799.
Wild RA, Umstot ES, Andersen RN, Ranney GB, Givens JR . Androgen parameters and their correlation with body weight in one hundred thirty-eight women thought to have hyperandrogenism. Am J Obstet Gynecol 1983; 146: 602–606.
Hoffman DI, Klove K, Lobo RA . The prevalence and significance of elevated dehydroepiandrosterone sulfate levels in anovulatory women. Fertil Steril 1984; 42: 76–81.
Steinberger E, Smith KD, Rodriguez-Rigau LJ . Testosterone, dehydroepiandrosterone, and dehydroepiandrosterone sulfate in hyperandrogenic women. J Clin Endocrinol Metab 1984; 59: 471–477.
Carmina E, Rosato F, Janni A . Increased DHEAs levels in PCO syndrome: evidence for the existence of two subgroups of patients. J Endocrinol Invest 1986; 9: 5–9.
Corton M, Botella-Carretero JI, Benguria A, Villuendas G, Zaballos A, San Millan JL et al. Differential gene expression profile in omental adipose tissue in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2007; 92: 328–337.
San Millan JL, Botella-Carretero JI, Alvarez-Blasco F, Luque-Ramirez M, Sancho J, Moghetti P et al. A study of the hexose-6-phosphate dehydrogenase gene R453Q and 11beta-hydroxysteroid dehydrogenase type 1 gene 83557insA polymorphisms in the polycystic ovary syndrome. J Clin Endocrinol Metab 2005; 90: 4157–4162.
White PC . Genotypes at 11beta-hydroxysteroid dehydrogenase type 11B1 and hexose-6-phosphate dehydrogenase loci are not risk factors for apparent cortisone reductase deficiency in a large population-based sample. J Clin Endocrinol Metab 2005; 90: 5880–5883.
Wake DJ, Rask E, Livingstone DE, Soderberg S, Olsson T, Walker BR . Local and systemic impact of transcriptional up-regulation of 11beta-hydroxysteroid dehydrogenase type 1 in adipose tissue in human obesity. J Clin Endocrinol Metab 2003; 88: 3983–3988.
Engeli S, Bohnke J, Feldpausch M, Gorzelniak K, Heintze U, Janke J et al. Regulation of 11beta-HSD genes in human adipose tissue: influence of central obesity and weight loss. Obes Res 2004; 12: 9–17.
Goedecke JH, Wake DJ, Levitt NS, Lambert EV, Collins MR, Morton NM et al. Glucocorticoid metabolism within superficial subcutaneous rather than visceral adipose tissue is associated with features of the metabolic syndrome in South African women. Clin Endocrinol (Oxf) 2006; 65: 81–87.
Low SC, Chapman KE, Edwards CR, Wells T, Robinson IC, Seckl JR . Sexual dimorphism of hepatic 11 beta-hydroxysteroid dehydrogenase in the rat: the role of growth hormone patterns. J Endocrinol 1994; 143: 541–548.
Jamieson PM, Nyirenda MJ, Walker BR, Chapman KE, Seckl JR . Interactions between oestradiol and glucocorticoid regulatory effects on liver-specific glucocorticoid-inducible genes: possible evidence for a role of hepatic 11beta-hydroxysteroid dehydrogenase type 1. J Endocrinol 1999; 160: 103–109.
Andrew R, Phillips DI, Walker BR . Obesity and gender influence cortisol secretion and metabolism in man. J Clin Endocrinol Metab 1998; 83: 1806–1809.
Raven PW, Taylor NF . Sex differences in the human metabolism of cortisol. Endocr Res 1996; 22: 751–755.
Weaver JU, Taylor NF, Monson JP, Wood PJ, Kelly WF . Sexual dimorphism in 11 beta hydroxysteroid dehydrogenase activity and its relation to fat distribution and insulin sensitivity; a study in hypopituitary subjects. Clin Endocrinol (Oxf) 1998; 49: 13–20.
Paulsen SK, Nielsen MP, Richelsen B, Bruun JM, Flyvbjerg A, Pedersen SB . Upregulation of adipose 11-beta-hydroxysteroid dehydrogenase type 1 expression in ovariectomized rats is due to obesity rather than lack of estrogen. Obesity (Silver Spring) 2008; 16: 731–735.
Barat P, Livingstone DE, Elferink CM, McDonnell CR, Walker BR, Andrew R . Effects of gonadectomy on glucocorticoid metabolism in obese Zucker rats. Endocrinology 2007; 148: 4836–4843.
Acknowledgements
We thank Susanne Reimar for technical assistance and ‘The Aage Bangs Foundation’ for economical support.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Svendsen, P., Madsbad, S., Nilas, L. et al. Expression of 11β-hydroxysteroid dehydrogenase 1 and 2 in subcutaneous adipose tissue of lean and obese women with and without polycystic ovary syndrome. Int J Obes 33, 1249–1256 (2009). https://doi.org/10.1038/ijo.2009.165
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/ijo.2009.165
Keywords
This article is cited by
-
Differences in expression of genes related to steroidgenesis in abdominal subcutaneous adipose tissue of pregnant women with and without PCOS; a case control study
BMC Pregnancy and Childbirth (2021)
-
Association of HSD11B1 polymorphic variants and adipose tissue gene expression with metabolic syndrome, obesity and type 2 diabetes mellitus: a systematic review
Diabetology & Metabolic Syndrome (2015)
-
Genetic variants of the HSD11B1 gene promoter may be protective against polycystic ovary syndrome
Molecular Biology Reports (2014)