Abstract
The activity of hydrocortisone, the major endogenous glucocorticoid in humans, is determined at multiple levels along a complex metabolic pathway that begins with the release of corticotropin releasing hormone (CRH) at the hypothalamus and ends in the nucleus of target cells where the activated glucocorticoid receptor regulates cellular functions. Modulation of glucocorticoid synthesis by the hypothalamic-pituitary-adrenal axis is described in detail in the chapter by Cowell and Buckingham. This chapter will examine how the activity of hydrocortisone may be controlled locally in various target tissues by the enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD).
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References
Persson CGA (1989) Glucocorticoids for asthma — early contributions. Pulmonary Pharmacol 2: 163–166
Monder C, White (PC) (1992) Biochemistry, molecular biology, and physiology of 11β-hydrox-ysteroid dehydrogenase. In: Edward CRW, DW Lincoln (eds): Recent advances in endocrinology and metabolism. Churchill Livingstone, Edinburgh, 4: 1–19
Lax ER, Ghraf R, Schriefers H (1978) The hormonal regulation of hepatic microsomal 11β hydroxysteroid dehydrogenase activity in the rat. Acta Endocrinol 89: 267
Tsigelny I, Baker ME (1995) Structures important in mammalian 11β and 17β-hydroxysteroid dehydrogenases. J Steroid Biochem Mol Biol 55: 589–600
Funder JW, Pearce PT, Smith R, Smith AI (1988) Mineralocorticoid action: target tissue specificity is enzyme, not receptor, mediated. Science 241: 340–349
Escher G, Galli I, Vishwanath BS, Frey BM, Frey FJ (1997) Tumor necrosis factor a and inter-leukin 1β enhance the cortisone/cortisol shuttle. J Exp Med 186: 189–198
Haigh RM, Jones CT, Milligan G (1990) Glucocorticoids regulate the amount of G proteins in rat aorta. J. Mol Endocrinol 5: 185–188
Rees DD, Cellek S, Palmer RMJ, Moncada S (1990) Dexamethasone prevents the induction by endotoxin of a nitric oxide synthase and the associated effects on vascular tone: an insight into endotoxic shock. Biochem Biophys Res Commun 173: 541–547
Walker BR, Connacher AA, Webb DJ, Edwards CRW (1992) Glucocorticoids and blood pressure: a role for the cortisol/cortisone shuttle in the control of vascular tone in man. Clin Sci 83: 171–178
Walker BR Stewart PM, Shackleton CHL, Padfield PL, Edwards CRW (1993) Deficient inactiva-tion of cortisol by 11β-hydroxysteroid dehydrogenase in essential hypertension. Clin Endocrinol 39: 221–227
Benediktsson R, Lindsay RS, Noble J, Seckl JR, Edwards CRW (1993) Glucocorticoid exposure in utero: a new model for adult hypertension. Lancet 341: 339–341
Lindsay RS, Lindsay RM, Edwards CRW, Seckl JR (1996) Inhibition of 11β-hydroxysteroid dehydrogenase in pregnant rats and the programming of blood pressure in the offspring. Hypertension 27: 1200–1204
Sapolsky R (1985) Stress-induced suppression of testicular function in the wild baboon: role of glucocorticoids. Endocrinology 116: 2273–2278
Schweiger U, Pirke KM, Laessle RG, Fitcher MM (1992) Gonadotropin secretion in bulemia ner-vosa. J Clin Endocrinol Metab 74: 1122–1127
Fateh M, Ben-Rafael Z, Benadiva CA, Mastroianni L, Flickinger GL (1989) Cortisol levels in human follicular fluid. Fertil Steril 51: 538–541
Murphy BE (1981) Ontogeny of cortisol-cortisone interconversion in human tissues: a role for cortisone in human fetal development. J Steroid Biochem 14: 811–817
Michael AE, Cooke BA (1994) A working hypothesis for the regulation of steroidogenesis and germ cell development in the gonads by glucocorticoids and 11 β-hydroxysteroid dehydrogenase. Mol Cell Endocrinol 100: 55–63
Michael AE, Gregory L, Walker SM, Antoniw JW, Shaw RW, Edwards CRW, Cooke BA (1993) Ovarian 11β-hydroxysterid dehydrogenase: potential predictor of conception by in vitro fertilisation and embryo transfer. Lancet 342: 711–712
Phillips DM, Lakshmi V, Monder C (1989) Corticosteroid 11β-dehydrogenase in rat testis. Endocrinology 125: 209–216
Liggins GC, Howie RN (1972) A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants. Pediatrics 50: 515–525
Hubbard WC, Bickel C, Schleimer RP (1994) Simultaneous quantitation of endogenous levels of cortisone and cortisol in human nasal and bronchoalveolar lavage fluids and plasma via gas chro-matography-negative ion chemical ionization mass spectrometry. Anal Biochem 221: 109–117
Feinstein MB, Schleimer RP (1999) Regulation of the action of hydrocortisone in airway epithelial cells by 11 β-hydroxy steroid dehydrogenase. Amer J Respir Cell Mol Biol 21: 403–408
Peebles RS, Bickel C, Brennan F, Hubbard W, Togias A, Schleimer RP (1996) Measurement of endogenous glucocorticoids in patients with asthma and in healthy subjects: relationship to allergen-induced changes in lung function. Amer J Respir Crit Care Med 153:A879
Sasaki H, Yanai M, Shimura S, Okayama H, Aikawa T, Sasaki T, Takishima T (1987) Late asthmatic response to Ascaris antigen challenge in dogs treated with metyrapone. Amer Rev Respir Dis 136: 1459–1465
Partridge M, Poswillo DE (1984) Topical carbenoxolone sodium in the management of herpes simplex infections. Brit J Oral Maxillofacial Surg 22: 138–145
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Feinstein, M.B., Schleimer, R.P. (2001). The role of 11β-hydroxysteroid dehydrogenase in regulating glucocorticoid action. In: Goulding, N.J., Flower, R.J. (eds) Glucocorticoids. Milestones in Drug Therapy MDT. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-8348-1_9
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DOI: https://doi.org/10.1007/978-3-0348-8348-1_9
Publisher Name: Birkhäuser, Basel
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Online ISBN: 978-3-0348-8348-1
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