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*Substance via MeSH
Medline Plus Health Information
*Steroids
Endocrine Reviews 19 (2): 101-143
Copyright © 1998 by The Endocrine Society

Intraadrenal Interactions in the Regulation of Adrenocortical Steroidogenesis

Monika Ehrhart-Bornstein, Joy P. Hinson, Stefan R. Bornstein, Werner A. Scherbaum and Gavin P. Vinson

Department of Internal Medicine III (M.E.-B.), University of Leipzig, 04103 Leipzig, Germany; Department of Biochemistry (J.P.H., G.P.V.), Queen Mary and Westfield College, London E14NS, England; National Institute of Child Health and Human Development (S.R.B.), National Institutes of Health, Bethesda, Maryland 20892; and Diabetes Research Institute at the Heinrich Heine University (W.A.S.), 40225 Düsseldorf, Germany

I. Introduction: The Adrenal Functional Unit
II. Interaction Between Adrenal Medulla and Adrenal Cortex
A. Relationship between medullary and cortical cells
B. Paracrine control of adrenocortical function by the adrenal medulla
C. Gap junctions in the adrenal cortex
D. Summary
III. Innervation of the Adrenal Cortex
A. Evidence for a nerve supply to the adrenal cortex
B. The source of adrenocortical innervation
C. Regulation of adrenocortical innervation
D. Role of the splanchnic nerve in regulating adrenocortical neural function
E. Influence of adrenal innervation on adrenocortical function
F. Effects of neurotransmitter substances on adrenocortical function
G. Summary
IV. The Vascular System of the Adrenal Gland
A. Regulation of blood flow
B. Relationship between blood flow and steroid secretion
C. Effects of vascular endothelial cell products on steroid secretion
D. Summary
V. The Intraadrenal CRH/ACTH System
A. Extrapituitary effect of CRH
B. Intraadrenal ACTH
C. Intraadrenal CRH and CRH receptors
D. Feedback mechanisms
E. Summary
VI. Immune Cells and Cytokines in the Adrenal Gland
A. Source of cytokines within the adrenal
B. Cytokines that influence the adrenal cortex
C. Summary
VII. Peptide Growth Factors and the Adrenal Cortex
A. FGFs
B. IGFs
C. TGFß
D. Summary
VIII. The Intraadrenal Renin-Angiotensin System (RAS)
A. The role of the RAS in adrenocortical function
B. Renin
C. Angiotensinogen
D. Angiotensin-converting enzyme and the production of angiotensin II
E. What is the functional significance of the intraadrenal RAS?
F. How can the angiotensin II produced by the tissue RAS be distinguished from the systemic system?
G. Summary
IX. Clinical Implications
A. Cortisol
B. Aldosterone
C. Adrenal androgens
D. Summary
X. Conclusions




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 J. Clin. Endocrinol. Metab.Home page
E. Charmandari, G. Eisenhofer, S. L. Mehlinger, A. Carlson, R. Wesley, M. F. Keil, G. P. Chrousos, M. I. New, and D. P. Merke
Adrenomedullary Function May Predict Phenotype and Genotype in Classic 21-Hydroxylase Deficiency
J. Clin. Endocrinol. Metab., July 1, 2002; 87(7): 3031 - 3037.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
C. C. Zouboulis, H. Seltmann, N. Hiroi, W. Chen, M. Young, M. Oeff, W. A. Scherbaum, C. E. Orfanos, S. M. McCann, and S. R. Bornstein
Corticotropin-releasing hormone: An autocrine hormone that promotes lipogenesis in human sebocytes
PNAS, May 14, 2002; 99(10): 7148 - 7153.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
S. Lenglet, E. Louiset, C. Delarue, H. Vaudry, and V. Contesse
Activation of 5-HT7 Receptor in Rat Glomerulosa Cells Is Associated with an Increase in Adenylyl Cyclase Activity and Calcium Influx through T-Type Calcium Channels
Endocrinology, May 1, 2002; 143(5): 1748 - 1760.
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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
K. Kojima, Y. Naruse, N. Iijima, N. Wakabayashi, S. Mitsufuji, Y. Ibata, and M. Tanaka
HPA-axis responses during experimental colitis in the rat
Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2002; 282(5): R1348 - R1355.
[Abstract] [Full Text] [PDF]

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 ANN INTERN MEDHome page
D. P. Merke, S. R. Bornstein, N. A. Avila, and G. P. Chrousos
Future Directions in the Study and Management of Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency
Ann Intern Med, February 19, 2002; 136(4): 320 - 334.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
N. Zuckerman-Levin, D. Tiosano, G. Eisenhofer, S. Bornstein, and Z.'e. Hochberg
The Importance of Adrenocortical Glucocorticoids for Adrenomedullary and Physiological Response to Stress: A Study in Isolated Glucocorticoid Deficiency
J. Clin. Endocrinol. Metab., December 1, 2001; 86(12): 5920 - 5924.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
J. Preil, M. B. Muller, A. Gesing, J. M. H. M. Reul, I. Sillaber, M. M. van Gaalen, J. Landgrebe, F. Holsboer, M. Stenzel-Poore, and W. Wurst
Regulation of the Hypothalamic-Pituitary-Adrenocortical System in Mice Deficient for CRH Receptors 1 and 2
Endocrinology, November 1, 2001; 142(11): 4946 - 4955.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
H. Lefebvre, P. Compagnon, V. Contesse, C. Delarue, C. Thuillez, H. Vaudry, and J.-M. Kuhn
Production and Metabolism of Serotonin (5-HT) by the Human Adrenal Cortex: Paracrine Stimulation of Aldosterone Secretion by 5-HT
J. Clin. Endocrinol. Metab., October 1, 2001; 86(10): 5001 - 5007.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
O. Johren, S. J. Neidert, M. Kummer, A. Dendorfer, and P. Dominiak
Prepro-Orexin and Orexin Receptor mRNAs Are Differentially Expressed in Peripheral Tissues of Male and Female Rats
Endocrinology, August 1, 2001; 142(8): 3324 - 3331.
[Abstract] [Full Text] [PDF]

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 FASEB J.Home page
A. SLOMINSKI, J. WORTSMAN, A. PISARCHIK, B. ZBYTEK, E. A. LINTON, J. E. MAZURKIEWICZ, and E. T. WEI
Cutaneous expression of corticotropin-releasing hormone (CRH), urocortin, and CRH receptors
FASEB J, August 1, 2001; 15(10): 1678 - 1693.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
N. Hiroi, G. P. Chrousos, B. Kohn, A. Lafferty, M. Abu-Asab, S. Bonat, A. White, and S. R. Bornstein
Adrenocortical-Pituitary Hybrid Tumor Causing Cushing's Syndrome
J. Clin. Endocrinol. Metab., June 1, 2001; 86(6): 2631 - 2637.
[Abstract] [Full Text] [PDF]

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 Endocr. Rev.Home page
A. Lacroix, N. N'Diaye, J. Tremblay, and P. Hamet
Ectopic and Abnormal Hormone Receptors in Adrenal Cushing's Syndrome
Endocr. Rev., February 1, 2001; 22(1): 75 - 110.
[Abstract] [Full Text]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
Y. M. Ulrich-Lai, C. A. Harding-Rose, A. Guo, W. R. Bowles, and W. C. Engeland
ACTH inhibits the capsaicin-evoked release of CGRP from rat adrenal afferent nerves
Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2001; 280(1): R137 - R142.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
S. R. Bornstein, H. Tian, A. Haidan, A. Bottner, N. Hiroi, G. Eisenhofer, S. M. McCann, G. P. Chrousos, and S. Roffler-Tarlov
Deletion of tyrosine hydroxylase gene reveals functional interdependence of adrenocortical and chromaffin cell system in vivo
PNAS, December 19, 2000; 97(26): 14742 - 14747.
[Abstract] [Full Text] [PDF]

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 NEJMHome page
D. P. Merke, G. P. Chrousos, G. Eisenhofer, M. Weise, M. F. Keil, A. D. Rogol, J. J. V. Wyk, and S. R. Bornstein
Adrenomedullary Dysplasia and Hypofunction in Patients with Classic 21-Hydroxylase Deficiency
N. Engl. J. Med., November 9, 2000; 343(19): 1362 - 1368.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
A. Bottner, A. Haidan, G. Eisenhofer, K. Kristensen, A. L. Castle, W. A. Scherbaum, H. Schneider, G. P. Chrousos, and S. R. Bornstein
Increased Body Fat Mass and Suppression of Circulating Leptin Levels in Response to Hypersecretion of Epinephrine in Phenylethanolamine-N-Methyltransferase (PNMT)-Overexpressing Mice
Endocrinology, November 1, 2000; 141(11): 4239 - 4246.
[Abstract] [Full Text] [PDF]

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 Physiol. Rev.Home page
A. Slominski, J. Wortsman, T. Luger, R. Paus, and S. Solomon
Corticotropin Releasing Hormone and Proopiomelanocortin Involvement in the Cutaneous Response to Stress
Physiol Rev, July 1, 2000; 80(3): 979 - 1020.
[Abstract] [Full Text] [PDF]

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 Endocr. Rev.Home page
P. C. White and P. W. Speiser
Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency
Endocr. Rev., June 1, 2000; 21(3): 245 - 291.
[Abstract] [Full Text]

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 EndocrinologyHome page
C. Le Roy, J. Y. Li, D. M. Stocco, D. Langlois, and J. M. Saez
Regulation by Adrenocorticotropin (ACTH), Angiotensin II, Transforming Growth Factor-{beta}, and Insulin-Like Growth Factor I of Bovine Adrenal Cell Steroidogenic Capacity and Expression of ACTH Receptor, Steroidogenic Acute Regulatory Protein, Cytochrome P450c17, and 3{beta}-Hydroxysteroid Dehydrogenase
Endocrinology, May 1, 2000; 141(5): 1599 - 1607.
[Abstract] [Full Text] [PDF]

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 Endocr. Rev.Home page
J. P. Hinson, S. Kapas, and D. M. Smith
Adrenomedullin, a Multifunctional Regulatory Peptide
Endocr. Rev., April 1, 2000; 21(2): 138 - 167.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
S. A. Murray, K. Davis, L. M. Fishman, and S. R. Bornstein
{alpha}1 Connexin 43 Gap Junctions Are Decreased in Human Adrenocortical Tumors
J. Clin. Endocrinol. Metab., February 1, 2000; 85(2): 890 - 895.
[Abstract] [Full Text]

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 Proc. Natl. Acad. Sci. USAHome page
M.-L. Wong, M. A. Kling, P. J. Munson, S. Listwak, J. Licinio, P. Prolo, B. Karp, I. E. McCutcheon, T. D. Geracioti Jr., M. D. DeBellis, et al.
Pronounced and sustained central hypernoradrenergic function in major depression with melancholic features: Relation to hypercortisolism and corticotropin-releasing hormone
PNAS, January 4, 2000; 97(1): 325 - 330.
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 EndocrinologyHome page
D. Renshaw, L. M. Thomson, M. Carroll, S. Kapas, and J. P. Hinson
Actions of Neuropeptide Y on the Rat Adrenal Cortex
Endocrinology, January 1, 2000; 141(1): 169 - 173.
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 EndocrinologyHome page
F.-J. Lai, S.-J. Shin, Y.-J. Lee, S.-R. Lin, W.-Y. Jou, and J.-H. Tsai
Up-Regulation of Adrenal Cortical and Medullary Atrial Natriuretic Peptide and Gene Expression in Rats with Deoxycorticosterone Acetate-Salt Treatment
Endocrinology, January 1, 2000; 141(1): 325 - 332.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
Corticotropin-Releasing Hormone: A Potent Androgen Secretagogue in Girls with Hyperandrogenism after Precocious Pubarche
J. Clin. Endocrinol. Metab., December 1, 1999; 84(12): 4602 - 4606.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
G. W. Wolkersdörfer, T. Lohmann, C. Marx, S. Schröder, R. Pfeiffer, H.-D. Stahl, W. A. Scherbaum, G. P. Chrousos, and S. R. Bornstein
Lymphocytes Stimulate Dehydroepiandrosterone Production through Direct Cellular Contact with Adrenal Zona Reticularis Cells: A Novel Mechanism of Immune-Endocrine Interaction
J. Clin. Endocrinol. Metab., November 1, 1999; 84(11): 4220 - 4227.
[Abstract] [Full Text]

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 Pharmacol. Rev.Home page
G. G. Nussdorfer, G. P. Rossi, L. K. Malendowicz, and G. Mazzocchi
Autocrine-Paracrine Endothelin System in the Physiology and Pathology of Steroid-Secreting Tissues
Pharmacol. Rev., September 1, 1999; 51(3): 403 - 438.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
T. Tajima, X.-M. Ma, S. R. Bornstein, and G. Aguilera
Prenatal Dexamethasone Treatment Does Not Prevent Alterations of the Hypothalamic Pituitary Adrenal Axis in Steroid 21-Hydroxylase Deficient Mice
Endocrinology, July 1, 1999; 140(7): 3354 - 3362.
[Abstract] [Full Text]

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 FASEB J.Home page
S. R. BORNSTEIN, T. TAJIMA, G. EISENHOFER, A. HAIDAN, and G. AGUILERA
Adrenomedullary function is severely impaired in 21-hydroxylase-deficient mice
FASEB J, July 1, 1999; 13(10): 1185 - 1194.
[Abstract] [Full Text]

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 ANN INTERN MEDHome page
S. R. Bornstein, C. A. Stratakis, and G. P. Chrousos
Adrenocortical Tumors: Recent Advances in Basic Concepts and Clinical Management
Ann Intern Med, May 4, 1999; 130(9): 759 - 771.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
S. R. Bornstein and G. P. Chrousos
Adrenocorticotropin (ACTH)- and Non-ACTH-Mediated Regulation of the Adrenal Cortex: Neural and Immune Inputs
J. Clin. Endocrinol. Metab., May 1, 1999; 84(5): 1729 - 1736.
[Full Text]

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 EndocrinologyHome page
M. M. Weber, C. Fottner, P. Schmidt, K. M. H. Brodowski, K. Gittner, H. Lahm, D. Engelhardt, and E. Wolf
Postnatal Overexpression of Insulin-Like Growth Factor II in Transgenic Mice Is Associated with Adrenocortical Hyperplasia and Enhanced Steroidogenesis
Endocrinology, April 1, 1999; 140(4): 1537 - 1543.
[Abstract] [Full Text]

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 HypertensionHome page
U. Hilbers, J. Peters, S. R. Bornstein, F. M. A. Correa, O. Johren, J. M. Saavedra, and M. Ehrhart-Bornstein
Local Renin-Angiotensin System Is Involved in K+-Induced Aldosterone Secretion from Human Adrenocortical NCI-H295 Cells
Hypertension, April 1, 1999; 33(4): 1025 - 1030.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
G. A. Hines and R. Azziz
Impact of Architectural Disruption on Adrenocortical Steroidogenesis In Vitro
J. Clin. Endocrinol. Metab., March 1, 1999; 84(3): 1017 - 1021.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
A. Glasow, A. Haidan, U. Hilbers, M. Breidert, J. Gillespie, W. A. Scherbaum, G. P. Chrousos, and S. R. Bornstein
Expression of Ob Receptor in Normal Human Adrenals: Differential Regulation of Adrenocortical and Adrenomedullary Function by Leptin
J. Clin. Endocrinol. Metab., December 1, 1998; 83(12): 4459 - 4466.
[Abstract] [Full Text]

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 NEJMHome page
H. S. Willenberg, C. A. Stratakis, C. Marx, M. Ehrhart-Bornstein, G. P. Chrousos, and S. R. Bornstein
Aberrant Interleukin-1 Receptors in a Cortisol-Secreting Adrenal Adenoma Causing Cushing's Syndrome
N. Engl. J. Med., July 2, 1998; 339(1): 27 - 31.
[Full Text] [PDF]


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