Skip to main content

Advertisement

Log in

The pituitary–adrenal axis and body composition

  • Published:
Pituitary Aims and scope Submit manuscript

Abstract

The activity of the pituitary–adrenal axis can profoundly impact on body composition. This is dramatically seen in Cushing’s syndrome (CS) but changes in body composition are also implicated in depression and alcoholic pseudocushing’s. The pathophysiological mechanisms underlying these changes remain poorly understood. Changes to body composition in CS include increased fat mass, decreased bone mass, thinning of the skin and reduced lean mass. Why these tissues are affected so dramatically is unclear. Additionally, the change in body composition between individuals varies considerably for reasons which are only now becoming evident. This paper reviews the phenotypic changes with altered pituitary–adrenal axis activity and discusses the mechanisms involved. The primary focus is on adipose, bone, muscle and skin since the most dramatic changes are seen in these tissues.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Mayo-Smith W, Hayes CW, Biller BM, Klibanski A, Rosenthal H, Rosenthal DI (1989) Body fat distribution measured with CT: correlations in healthy subjects, patients with anorexia nervosa, and patients with Cushing syndrome. Radiology 170:515–518. Medline

    PubMed  CAS  Google Scholar 

  2. Burt MG, Gibney J, Ho KK (2006) Characterization of the metabolic phenotypes of Cushing’s syndrome and growth hormone deficiency: a study of body composition and energy metabolism. Clin Endocrinol (Oxf) 64:436–443. Medline. doi:10.1111/j.1365–2265.2006.02488.x

    Google Scholar 

  3. Wajchenberg BL, Bosco A, Marone MM et al (1995) Estimation of body fat and lean tissue distribution by dual energy X-ray absorptiometry and abdominal body fat evaluation by computed tomography in Cushing’s disease. J Clin Endocrinol Metab 80:2791–2794. Medline. doi:10.1210/jc.80.9.2791

    PubMed  CAS  Google Scholar 

  4. Garrapa GG, Pantanetti P, Arnaldi G, Mantero F, Faloia E (2001) Body composition and metabolic features in women with adrenal incidentaloma or Cushing’s syndrome. J Clin Endocrinol Metab 86:5301–5306. Medline. doi:10.1210/jc.86.11.5301

    PubMed  CAS  Google Scholar 

  5. Rockall AG, Sohaib SA, Evans D et al (2003) Hepatic steatosis in Cushing’s syndrome: a radiological assessment using computed tomography. Eur J Endocrinol 149:543–548. Medline. doi:10.1530/eje.0.1490543

    PubMed  CAS  Google Scholar 

  6. Zoppini G, Targher G, Venturi C, Zamboni C, Muggeo M (2004) Relationship of nonalcoholic hepatic steatosis to overnight low-dose dexamethasone suppression test in obese individuals. Clin Endocrinol (Oxf) 61:711–715. Medline. doi:10.1111/j.1365–2265.2004.02154.x

    Google Scholar 

  7. Paulsen SK, Pedersen SB, Fisker S, Richelsen B (2007) 11Beta-HSD type 1 expression in human adipose tissue: impact of gender, obesity, and fat localization. Obesity (Silver Spring) 15:1954–1960. Medline

    CAS  Google Scholar 

  8. Rebuffe-Scrive M, Krotkiewski M, Elfverson J, Bjorntorp P (1988) Muscle and adipose tissue morphology and metabolism in Cushing’s syndrome. J Clin Endocrinol Metab 67:1122–1128. Medline

    PubMed  CAS  Google Scholar 

  9. Gravholt CH, Dall R, Christiansen JS, Moller N, Schmitz O (2002) Preferential stimulation of abdominal subcutaneous lipolysis after prednisolone exposure in humans. Obes Res 10:774–781. Medline

    PubMed  CAS  Google Scholar 

  10. Fried SK, Russell CD, Grauso NL, Brolin RE (1993) Lipoprotein lipase regulation by insulin and glucocorticoid in subcutaneous and omental adipose tissues of obese women and men. J Clin Invest 92:2191–2198. Medline

    PubMed  CAS  Google Scholar 

  11. Tanaka H, Ichikawa Y, Akama H, Homma M (1989) In vivo responsiveness to glucocorticoid correlated with glucocorticoid receptor content in peripheral blood leukocytes in normal humans. Acta Endocrinol (Copenh) 121:470–476. Medline

    CAS  Google Scholar 

  12. Issekutz B Jr, Borkow I (1972) Effect of catecholamines and dibutyryl-cyclic-AMP on glucose turnover, plasma free fatty acids, and insulin in dogs treated with methylprednisolone. Can J Physiol Pharmacol 50:999–1006. Medline

    PubMed  CAS  Google Scholar 

  13. Ahdjoudj S, Lasmoles F, Oyajobi BO, Lomri A, Delannoy P, Marie PJ (2001) Reciprocal control of osteoblast/chondroblast and osteoblast/adipocyte differentiation of multipotential clonal human marrow stromal F/STRO-1(+) cells. J Cell Biochem 81:23–38. Medline. doi:10.1002/1097-4644(20010401)81:1≤23::AID-JCB1021≥3.0.CO;2-H

    PubMed  CAS  Google Scholar 

  14. Bujalska IJ, Kumar S, Hewison M, Stewart PM (1999) Differentiation of adipose stromal cells: the roles of glucocorticoids and 11beta-hydroxysteroid dehydrogenase. Endocrinology 140:3188–3196. Medline. doi:10.1210/en.140.7.3188

    PubMed  CAS  Google Scholar 

  15. MacDougald OA, Lane MD (1995) Transcriptional regulation of gene expression during adipocyte differentiation. Annu Rev Biochem 64:345–373. Medline. doi:10.1146/annurev.bi.64.070195.002021

    PubMed  CAS  Google Scholar 

  16. Ottosson M, Lonnroth P, Bjorntorp P, Eden S (2000) Effects of cortisol and growth hormone on lipolysis in human adipose tissue. J Clin Endocrinol Metab 85:799–803. Medline. doi:10.1210/jc.85.2.799

    PubMed  CAS  Google Scholar 

  17. Mancini T, Doga M, Mazziotti G, Giustina A (2004) Cushing’s syndrome and bone. Pituitary 7:249–252. Medline. doi:10.1007/s11102-005-1051-2

    PubMed  Google Scholar 

  18. Ueland T, Kristo C, Godang K, Aukrust P, Bollerslev J (2003) Interleukin-1 receptor antagonist is associated with fat distribution in endogenous Cushing’s syndrome: a longitudinal study. J Clin Endocrinol Metab 88:1492–1496. Medline. doi:10.1210/jc.2002-021030

    PubMed  CAS  Google Scholar 

  19. Halleux CM, Servais I, Reul BA, Detry R, Brichard SM (1998) Multihormonal control of ob gene expression and leptin secretion from cultured human visceral adipose tissue: increased responsiveness to glucocorticoids in obesity. J Clin Endocrinol Metab 83:902–910. Medline. doi:10.1210/jc.83.3.902

    PubMed  CAS  Google Scholar 

  20. Stewart PM, Tomlinson JW (2002) Cortisol, 11 beta-hydroxysteroid dehydrogenase type 1 and central obesity. Trends Endocrinol Metab 13:94–96. Medline. doi:10.1016/S1043-2760(02)00566-0

    PubMed  CAS  Google Scholar 

  21. Bujalska IJ, Kumar S, Stewart PM (1997) Does central obesity reflect “Cushing’s disease of the omentum”? Lancet. 349:1210–1213. Medline. doi:10.1016/S0140-6736(96)11222-8

    PubMed  CAS  Google Scholar 

  22. Masuzaki H, Paterson J, Shinyama H et al (2001) A transgenic model of visceral obesity and the metabolic syndrome. Science 294:2166–2170. Medline. doi:10.1126/science.1066285

    PubMed  CAS  Google Scholar 

  23. Rask E, Walker BR, Soderberg S et al (2002) Tissue-specific changes in peripheral cortisol metabolism in obese women: increased adipose 11beta-hydroxysteroid dehydrogenase type 1 activity. J Clin Endocrinol Metab 87:3330–3336. Medline. doi:10.1210/jc.87.7.3330

    PubMed  CAS  Google Scholar 

  24. Engeli S, Bohnke J, Feldpausch M et al (2004) Regulation of 11beta-HSD genes in human adipose tissue: influence of central obesity and weight loss. Obes Res 12:9–17. Medline

    PubMed  CAS  Google Scholar 

  25. Sandeep TC, Andrew R, Homer NZ, Andrews RC, Smith K, Walker BR (2005) Increased in vivo regeneration of cortisol in adipose tissue in human obesity and effects of the 11beta-hydroxysteroid dehydrogenase type 1 inhibitor carbenoxolone. Diabetes 54:872–879. Medline. doi:10.2337/diabetes.54.3.872

    PubMed  CAS  Google Scholar 

  26. Tomlinson JW, Moore JS, Clark PM, Holder G, Shakespeare L, Stewart PM (2004) Weight loss increases 11beta-hydroxysteroid dehydrogenase type 1 expression in human adipose tissue. J Clin Endocrinol Metab 89:2711–2716. Medline. doi:10.1210/jc.2003-031376

    PubMed  CAS  Google Scholar 

  27. Draper N, Walker EA, Bujalska IJ et al (2003) Mutations in the genes encoding 11beta-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase interact to cause cortisone reductase deficiency. Nat Genet 34:434–439. Medline. doi:10.1038/ng1214

    PubMed  CAS  Google Scholar 

  28. Rebuffe-Scrive M, Bronnegard M, Nilsson A, Eldh J, Gustafsson JA, Bjorntorp P (1990) Steroid hormone receptors in human adipose tissues. J Clin Endocrinol Metab 71:1215–1219. Medline

    Article  PubMed  CAS  Google Scholar 

  29. Rebuffe-Scrive M, Lundholm K, Bjorntorp P (1985) Glucocorticoid hormone binding to human adipose tissue. Eur J Clin Invest 15:267–271. Medline

    PubMed  CAS  Google Scholar 

  30. Bujalska IJ, Quinkler M, Tomlinson JW, Montague CT, Smith DM, Stewart PM (2006) Expression profiling of 11beta-hydroxysteroid dehydrogenase type-1 and glucocorticoid-target genes in subcutaneous and omental human preadipocytes. J Mol Endocrinol 37:327–340. Medline. doi:10.1677/jme.1.02048

    PubMed  CAS  Google Scholar 

  31. Dobson MG, Redfern CP, Unwin N, Weaver JU (2001) The N363S polymorphism of the glucocorticoid receptor: potential contribution to central obesity in men and lack of association with other risk factors for coronary heart disease and diabetes mellitus. J Clin Endocrinol Metab 86:2270–2274. Medline. doi:10.1210/jc.86.5.2270

    PubMed  CAS  Google Scholar 

  32. Fraser R, Ingram MC, Anderson NH, Morrison C, Davies E, Connell JM (1999) Cortisol effects on body mass, blood pressure, and cholesterol in the general population. Hypertension 33:1364–1368. Medline

    PubMed  CAS  Google Scholar 

  33. Dimitriou T, Maser-Gluth C, Remer T (2003) Adrenocortical activity in healthy children is associated with fat mass. Am J Clin Nutr 77:731–736. Medline

    PubMed  CAS  Google Scholar 

  34. Marin P, Darin N, Amemiya T, Andersson B, Jern S, Bjorntorp P (1992) Cortisol secretion in relation to body fat distribution in obese premenopausal women. Metabolism 41:882–886. Medline. doi:10.1016/0026–0495(92)90171-6

    PubMed  CAS  Google Scholar 

  35. Stewart PM, Boulton A, Kumar S, Clark PM, Shackleton CH (1999) Cortisol metabolism in human obesity: impaired cortisone–>cortisol conversion in subjects with central adiposity. J Clin Endocrinol Metab 84:1022–1027. Medline. doi:10.1210/jc.84.3.1022

    PubMed  CAS  Google Scholar 

  36. Pasquali R, Vicennati V (2000) The abdominal obesity phenotype and insulin resistance are associated with abnormalities of the hypothalamic-pituitary-adrenal axis in humans. Horm Metab Res 32:521–525. Medline

    Article  PubMed  CAS  Google Scholar 

  37. Travison TG, O’Donnell AB, Araujo AB, Matsumoto AM, McKinlay JB (2007) Cortisol levels and measures of body composition in middle-aged and older men. Clin Endocrinol (Oxf) 67:71–77. Medline. doi:10.1111/j.1365-2265.2007.02837.x

    CAS  Google Scholar 

  38. Jessop DS, Dallman MF, Fleming D, Lightman SL (2001) Resistance to glucocorticoid feedback in obesity. J Clin Endocrinol Metab 86:4109–4114. Medline. doi:10.1210/jc.86.9.4109

    PubMed  CAS  Google Scholar 

  39. Purnell JQ, Brandon DD, Isabelle LM, Loriaux DL, Samuels MH (2004) Association of 24-hour cortisol production rates, cortisol-binding globulin, and plasma-free cortisol levels with body composition, leptin levels, and aging in adult men and women. J Clin Endocrinol Metab 89:281–287. Medline. doi:10.1210/jc.2003-030440

    PubMed  CAS  Google Scholar 

  40. Ohmori N, Nomura K, Ohmori K, Kato Y, Itoh T, Takano K (2003) Osteoporosis is more prevalent in adrenal than in pituitary Cushing’s syndrome. Endocr J 50:1–7. Medline. doi:10.1507/endocrj.50.1

    PubMed  Google Scholar 

  41. Yoshihara A, Okubo Y, Tanabe A et al (2007) A juvenile case of Cushing’s disease incidentally discovered with multiple bone fractures. Intern Med 46:583–587. Medline. doi:10.2169/internalmedicine.46.1824

    PubMed  Google Scholar 

  42. Kaltsas G, Manetti L, Grossman AB (2002) Osteoporosis in Cushing’s syndrome. Front Horm Res 30:60–72. Medline

    PubMed  CAS  Google Scholar 

  43. Kristo C, Jemtland R, Ueland T, Godang K, Bollerslev J (2006) Restoration of the coupling process and normalization of bone mass following successful treatment of endogenous Cushing’s syndrome: a prospective, long-term study. Eur J Endocrinol 154:109–118. Medline. doi:10.1530/eje.1.02067

    PubMed  CAS  Google Scholar 

  44. van Staa TP, Leufkens HG, Abenhaim L, Zhang B, Cooper C (2000) Use of oral corticosteroids and risk of fractures. J Bone Miner Res 15:993–1000. Medline. doi:10.1359/jbmr.2000.15.6.993

    PubMed  Google Scholar 

  45. Cooper MS (2004) Sensitivity of bone to glucocorticoids. Clin Sci (Lond) 107:111–123. Medline. doi:10.1042/CS20040070

    Article  CAS  Google Scholar 

  46. Tauchmanova L, Rossi R, Nuzzo V et al (2001) Bone loss determined by quantitative ultrasonometry correlates inversely with disease activity in patients with endogenous glucocorticoid excess due to adrenal mass. Eur J Endocrinol 145:241–247. Medline. doi:10.1530/eje.0.1450241

    PubMed  CAS  Google Scholar 

  47. Godang K, Ueland T, Bollerslev J (1999) Decreased bone area, bone mineral content, formative markers, and increased bone resorptive markers in endogenous Cushing’s syndrome. Eur J Endocrinol 141:126–131. Medline. doi:10.1530/eje.0.1410126

    PubMed  CAS  Google Scholar 

  48. Minetto M, Reimondo G, Osella G, Ventura M, Angeli A, Terzolo M (2004) Bone loss is more severe in primary adrenal than in pituitary-dependent Cushing’s syndrome. Osteoporos Int 15:855–861. Medline. doi:10.1007/s00198-004-1616-3

    PubMed  CAS  Google Scholar 

  49. Di Somma C, Pivonello R, Loche S et al (2003) Effect of 2 years of cortisol normalization on the impaired bone mass and turnover in adolescent and adult patients with Cushing’s disease: a prospective study. Clin Endocrinol (Oxf) 58:302–308. Medline. doi:10.1046/j.1365-2265.2003.01713.x

    CAS  Google Scholar 

  50. Di Somma C, Pivonello R, Loche S et al (2002) Severe impairment of bone mass and turnover in Cushing’s disease: comparison between childhood-onset and adulthood-onset disease. Clin Endocrinol (Oxf) 56:153-158. Medline. doi:10.1046/j.0300-0664.2001.01454.doc.x

    Google Scholar 

  51. Chiodini I, Carnevale V, Torlontano M et al (1998) Alterations of bone turnover and bone mass at different skeletal sites due to pure glucocorticoid excess: study in eumenorrheic patients with Cushing’s syndrome. J Clin Endocrinol Metab 83:1863–1867. Medline. doi:10.1210/jc.83.6.1863

    PubMed  CAS  Google Scholar 

  52. Gennari C, Imbimbo B. (1985) Effects of prednisone and deflazacort on vertebral bone mass. Calcif Tissue Int 37:592–593. Medline. doi:10.1007/BF02554912

    PubMed  CAS  Google Scholar 

  53. van der Eerden AW, den Heijer M, Oyen WJ, Hermus AR (2007) Cushing’s syndrome and bone mineral density: lowest Z scores in young patients. Neth J Med 65:137–141. Medline

    PubMed  Google Scholar 

  54. Hermus AR, Smals AG, Swinkels LM et al (1995) Bone mineral density and bone turnover before and after surgical cure of Cushing’s syndrome. J Clin Endocrinol Metab 80:2859–2865. Medline. doi:10.1210/jc.80.10.2859

    PubMed  CAS  Google Scholar 

  55. Leong GM, Abad V, Charmandari E et al (2007) Effects of child- and adolescent-onset endogenous Cushing syndrome on bone mass, body composition, and growth: a 7-year prospective study into young adulthood. J Bone Miner Res 22:110–118. Medline. doi:10.1359/jbmr.061010

    PubMed  Google Scholar 

  56. Faggiano A, Pivonello R, Filippella M et al (2001) Spine abnormalities and damage in patients cured from Cushing’s disease. Pituitary 4:153–161. Medline. doi:10.1023/A:1015362822901

    PubMed  CAS  Google Scholar 

  57. Chiodini I, Mascia ML, Muscarella S et al (2007) Subclinical hypercortisolism among outpatients referred for osteoporosis. Ann Intern Med 147:541–548. Medline

    PubMed  Google Scholar 

  58. Cooper MS, Blumsohn A, Goddard PE et al (2003) 11beta-hydroxysteroid dehydrogenase type 1 activity predicts the effects of glucocorticoids on bone. J Clin Endocrinol Metab 88:3874–3877. Medline. doi:10.1210/jc.2003-022025

    PubMed  CAS  Google Scholar 

  59. Godschalk MF, Downs RW (1988) Effect of short-term glucocorticoids on serum osteocalcin in healthy young men. J Bone Miner Res 3:113–115. Medline

    Article  PubMed  CAS  Google Scholar 

  60. Francucci CM, Pantanetti P, Garrapa GG, Massi F, Arnaldi G, Mantero F (2002) Bone metabolism and mass in women with Cushing’s syndrome and adrenal incidentaloma. Clin Endocrinol (Oxf) 57:587–593. Medline. doi:10.1046/j.1365-2265.2002.01602.x

    CAS  Google Scholar 

  61. Canalis E (1996) Clinical review 83: Mechanisms of glucocorticoid action in bone: implications to glucocorticoid-induced osteoporosis. J Clin Endocrinol Metab 81:3441–3447. Medline. doi:10.1210/jc.81.10.3441

    PubMed  CAS  Google Scholar 

  62. Karavitaki N, Ioannidis G, Giannakopoulos F, Mavrokefalos P, Thalassinos N (2004) Evaluation of bone mineral density of the peripheral skeleton in pre- and postmenopausal women with newly diagnosed endogenous Cushing’s syndrome. Clin Endocrinol (Oxf) 60:264–270. Medline. doi:10.1111/j.1365-2265.2004.01968.x

    CAS  Google Scholar 

  63. Canalis E, Bilezikian JP, Angeli A, Giustina A (2004) Perspectives on glucocorticoid-induced osteoporosis. Bone 34:593–598. Medline. doi:10.1016/j.bone.2003.11.026

    PubMed  CAS  Google Scholar 

  64. Cooper MS, Hewison M, Stewart PM (1999) Glucocorticoid activity, inactivity and the osteoblast. J Endocrinol 163:159–164. Medline. doi:10.1677/joe.0.1630159

    PubMed  CAS  Google Scholar 

  65. Weinstein RS, Jilka RL, Parfitt AM, Manolagas SC (1998) Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone. J Clin Invest 102:274–282. Medline. doi:10.1172/JCI2799

    PubMed  CAS  Google Scholar 

  66. Eijken M, Hewison M, Cooper MS et al (2005) 11beta-Hydroxysteroid dehydrogenase expression and glucocorticoid synthesis are directed by a molecular switch during osteoblast differentiation. Mol Endocrinol 19:621–631. Medline. doi:10.1210/me.2004-0212

    PubMed  CAS  Google Scholar 

  67. Cooper MS, Bujalska I, Rabbitt E et al (2001) Modulation of 11beta-hydroxysteroid dehydrogenase isozymes by proinflammatory cytokines in osteoblasts: an autocrine switch from glucocorticoid inactivation to activation. J Bone Miner Res 16:1037–1044. Medline. doi:10.1359/jbmr.2001.16.6.1037

    PubMed  CAS  Google Scholar 

  68. Newell-Price J, Trainer P, Besser M, Grossman A (1998) The diagnosis and differential diagnosis of Cushing’s syndrome and pseudo-Cushing’s states. Endocr Rev 19:647–672. Medline. doi:10.1210/er.19.5.647

    PubMed  CAS  Google Scholar 

  69. Muller R, Kugelberg E (1959) Myopathy in Cushing’s syndrome. J Neurol Neurosurg Psychiatry 22:314–319. Medline

    PubMed  CAS  Google Scholar 

  70. Lane RJ, Mastaglia FL (1978) Drug-induced myopathies in man. Lancet 2:562–566. Medline. doi:10.1016/S0140-6736(78)92894-5

    PubMed  CAS  Google Scholar 

  71. Mills GH, Kyroussis D, Jenkins P et al (1999) Respiratory muscle strength in Cushing’s syndrome. Am J Respir Crit Care Med 160:1762–1765. Medline

    PubMed  CAS  Google Scholar 

  72. Khaleeli AA, Edwards RH, Gohil K et al (1983) Corticosteroid myopathy: a clinical and pathological study. Clin Endocrinol (Oxf) 18:155–166. Medline

    CAS  Google Scholar 

  73. Khaleeli AA, Betteridge DJ, Edwards RH, Round JM, Ross EJ (1983) Effect of treatment of Cushing’s syndrome on skeletal muscle structure and function. Clin Endocrinol (Oxf) 19:547–556. Medline

    CAS  Google Scholar 

  74. Kendall-Taylor P, Turnbull DM (1983) Endocrine myopathies. Br Med J (Clin Res Ed) 287:705–708. Medline

    CAS  Google Scholar 

  75. Djaldetti M, Gafter U, Fishman P (1977) Ultrastructural observations in myopathy complicating Cushing’s disease. Am J Med Sci 273:273–277. Medline

    PubMed  CAS  Google Scholar 

  76. Jang C, Obeyesekere VR, Dilley RJ, Alford FP, Inder WJ (2006) 11Beta hydroxysteroid dehydrogenase type 1 is expressed and is biologically active in human skeletal muscle. Clin Endocrinol (Oxf) 65:800–805. Medline. doi:10.1111/j.1365-2265.2006.02669.x

    CAS  Google Scholar 

  77. Whorwood CB, Donovan SJ, Wood PJ, Phillips DI (2001) Regulation of glucocorticoid receptor alpha and beta isoforms and type I 11beta-hydroxysteroid dehydrogenase expression in human skeletal muscle cells: a key role in the pathogenesis of insulin resistance? J Clin Endocrinol Metab 86:2296–2308. Medline. doi:10.1210/jc.86.5.2296

    PubMed  CAS  Google Scholar 

  78. Tomlinson JW, Moore J, Cooper MS et al (2001) Regulation of expression of 11beta-hydroxysteroid dehydrogenase type 1 in adipose tissue: tissue-specific induction by cytokines. Endocrinology 142:1982–1989. Medline. doi:10.1210/en.142.5.1982

    PubMed  CAS  Google Scholar 

  79. Fitts RH, Romatowski JG, Peters JR, Paddon-Jones D, Wolfe RR, Ferrando AA (2007) The deleterious effects of bed rest on human skeletal muscle fibers are exacerbated by hypercortisolemia and ameliorated by dietary supplementation. Am J Physiol Cell Physiol 293:C313-C320. Medline. doi:10.1152/ajpcell.00573.2006

    PubMed  CAS  Google Scholar 

  80. Louard RJ, Bhushan R, Gelfand RA, Barrett EJ, Sherwin RS (1994) Glucocorticoids antagonize insulin’s antiproteolytic action on skeletal muscle in humans. J Clin Endocrinol Metab 79:278–284. Medline. doi:10.1210/jc.79.1.278

    PubMed  CAS  Google Scholar 

  81. Hong DH, Forsberg NE (1995) Effects of dexamethasone on protein degradation and protease gene expression in rat L8 myotube cultures. Mol Cell Endocrinol 108:199–209. Medline. doi:10.1016/0303-7207(95)03476-N

    PubMed  CAS  Google Scholar 

  82. Joulia-Ekaza D, Cabello G (2007) The myostatin gene: physiology and pharmacological relevance. Curr Opin Pharmacol 7:310-315. Medline. doi:10.1016/j.coph.2006.11.011

    PubMed  CAS  Google Scholar 

  83. Ma K, Mallidis C, Bhasin S et al (2003) Glucocorticoid-induced skeletal muscle atrophy is associated with upregulation of myostatin gene expression. Am J Physiol Endocrinol Metab 285:E363–E371. Medline

    PubMed  CAS  Google Scholar 

  84. Gilson H, Schakman O, Combaret L et al (2007) Myostatin gene deletion prevents glucocorticoid-induced muscle atrophy. Endocrinology 148:452–460. Medline. doi:10.1210/en.2006-0539

    PubMed  CAS  Google Scholar 

  85. Dardevet D, Sornet C, Taillandier D, Savary I, Attaix D, Grizard J (1995) Sensitivity and protein turnover response to glucocorticoids are different in skeletal muscle from adult and old rats. Lack of regulation of the ubiquitin-proteasome proteolytic pathway in aging. J Clin Invest 96:2113–2119. Medline

    PubMed  CAS  Google Scholar 

  86. Rieu I, Sornet C, Grizard J, Dardevet D (2004) Glucocorticoid excess induces a prolonged leucine resistance on muscle protein synthesis in old rats. Exp Gerontol 39:1315–1321. Medline. doi:10.1016/j.exger.2004.06.005

    PubMed  CAS  Google Scholar 

  87. Seene T, Kaasik P, Pehme A, Alev K, Riso EM (2003) The effect of glucocorticoids on the myosin heavy chain isoforms’ turnover in skeletal muscle. J Steroid Biochem Mol Biol 86:201–206. Medline. doi:10.1016/j.jsbmb.2003.08.002

    PubMed  CAS  Google Scholar 

  88. Pirlich M, Biering H, Gerl H et al (2002) Loss of body cell mass in Cushing’s syndrome: effect of treatment. J Clin Endocrinol Metab 87:1078–1084. Medline. doi:10.1210/jc.87.3.1078

    PubMed  CAS  Google Scholar 

  89. Ahtikoski AM, Riso EM, Koskinen SO, Risteli J, Takala TE (2004) Regulation of type IV collagen gene expression and degradation in fast and slow muscles during dexamethasone treatment and exercise. Pflugers Arch 448:123–130. Medline. doi:10.1007/s00424–003–1226–5

    PubMed  CAS  Google Scholar 

  90. Manoli I, Le H, Alesci S et al (2005) Monoamine oxidase-A is a major target gene for glucocorticoids in human skeletal muscle cells. FASEB J 19:1359–1361. Medline

    PubMed  CAS  Google Scholar 

  91. Giustina A, Veldhuis JD (1998) Pathophysiology of the neuroregulation of growth hormone secretion in experimental animals and the human. Endocr Rev 19:717–797. Medline. doi:10.1210/er.19.6.717

    PubMed  CAS  Google Scholar 

  92. Johannsson G, Sunnerhagen KS, Svensson J (2004) Baseline characteristics and the effects of two years of growth hormone replacement therapy in adults with growth hormone deficiency previously treated for Cushing’s disease. Clin Endocrinol (Oxf) 60:550–559. Medline. doi:10.1111/j.1365-2265.2004.02018.x

    CAS  Google Scholar 

  93. Phillips PJ, Weightman W (2007) Skin and Cushing syndrome. Aust Fam Physician 36:545–547. Medline

    PubMed  Google Scholar 

  94. Stratakis CA, Mastorakos G, Mitsiades NS, Mitsiades CS, Chrousos GP (1998) Skin manifestations of Cushing disease in children and adolescents before and after the resolution of hypercortisolemia. Pediatr Dermatol 15:253–258. Medline. doi:10.1046/j.1525-1470.1998.1998015253.x

    PubMed  CAS  Google Scholar 

  95. Reich A, Bednarek-Tupikowska Z, Czarnecka A, Szepietowski JC (2006) Cutaneous manifestations in a patient with a long-term history of untreated ACTH-dependent Cushing’s syndrome. Acta Dermatovenerol Croat 14:30–34. Medline

    PubMed  Google Scholar 

  96. Groves RW, MacDonald LM, MacDonald DM (1990) Profound digital collagen atrophy: a new cutaneous presentation of adrenal-dependent Cushing’s syndrome. Br J Dermatol 123:667–671. Medline. doi:10.1111/j.1365-2133.1990.tb01486.x

    PubMed  CAS  Google Scholar 

  97. Kletsas D, Pratsinis H, Gioni V, Pilichos K, Yiacoumettis AM, Tsagarakis S (2007) Prior chronic in vivo glucocorticoid excess leads to an anabolic phenotype and an extension of cellular life span of skin fibroblasts in vitro. Ann N Y Acad Sci 1100:449–454. Medline. doi:10.1196/annals.1395.050

    PubMed  CAS  Google Scholar 

  98. van Rossum EF, Lamberts SW (2004) Polymorphisms in the glucocorticoid receptor gene and their associations with metabolic parameters and body composition. Recent Prog Horm Res 59:333–357. Medline. doi:10.1210/rp.59.1.333

    PubMed  Google Scholar 

  99. Tomlinson JW, Draper N, Mackie J et al (2002) Absence of Cushingoid phenotype in a patient with Cushing’s disease due to defective cortisone to cortisol conversion. J Clin Endocrinol Metab 87:57–62. Medline. doi:10.1210/jc.87.1.57

    PubMed  CAS  Google Scholar 

  100. Oreffo RO, Cooper C, Mason C, Clements M (2005) Mesenchymal stem cells: lineage, plasticity, and skeletal therapeutic potential. Stem Cell Rev 1:169–178. Medline. doi:10.1385/SCR:1:2:169

    PubMed  CAS  Google Scholar 

  101. Oshina H, Sotome S, Yoshii T et al (2007) Effects of continuous dexamethasone treatment on differentiation capabilities of bone marrow-derived mesenchymal cells. Bone 41:575–583. Medline. doi:10.1016/j.bone.2007.06.022

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Paul M. Stewart.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fernandez-Rodriguez, E., Stewart, P.M. & Cooper, M.S. The pituitary–adrenal axis and body composition. Pituitary 12, 105–115 (2009). https://doi.org/10.1007/s11102-008-0098-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11102-008-0098-2

Keywords

Navigation