| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Departments of Clinical Biochemistry and Medicine (A.P.C., B.G.C., G.S.H.Y., K.S., S.J.P., D.H., S.O.), Cambridge Institute for Medical Research, Addenbrooke’s Hospital, Cambridge CB2 2XY, United Kingdom; and Paradigm Therapeutics (R.R.T.), Cambridge CB4 0WA, United Kingdom
Address all correspondence and requests for reprints to: Stephen O’Rahilly, University Departments of Medicine and Clinical Biochemistry, Box 232, Addenbrooke’s Hospital, Cambridge CB2 2QR, United Kingdom. E-mail: sorahill{at}hgmp.mrc.ac.uk.
The mature adrenal cortex is dependent upon proopiomelanocortin (POMC)-derived peptides for the maintenance of its size, structure, and endocrine function. Recent studies in mice genetically deficient in POMC have suggested that early exposure to POMC-derived peptides might also be necessary for the development of a functionally competent adrenal. We examined adrenal morphology and function in an independent line of mice lacking all POMC-derived peptides (Pomc–/–). Adrenal glands were found in all mice, although the glands of Pomc–/– mice had markedly reduced weight compared with control animals (0.5 ± 0.1 vs. 2.1 ± 0.1 mg, respectively; P < 0.05) and had disrupted cortical architecture. In Pomc–/– mice, plasma corticosterone was undetectable, and plasma aldosterone was significantly reduced compared with wild-type mice (498 ± 88 vs. 1845 ± 168 nmol/liter, respectively; P < 0.001). Heterozygous mice (Pomc+/–) had smaller adrenal glands with significantly lower levels of corticosterone both basally and in response to CRH and ACTH than wild-type mice, indicating that two functional copies of the Pomc gene are necessary to support the fully normal function of the hypothalamic-pituitary-adrenal axis. Three-month-old Pomc–/– mice were treated for 10 d with a highly specific ACTH analog. This treatment restored adrenal weight, cortical morphology, and plasma corticosterone to the levels seen in wild-type littermates. In conclusion, murine adrenal glands can develop without exposure to endogenous POMC-derived peptides during fetal and neonatal life. Although such glands are atrophic and hypofunctional, exposure to ACTH alone can restore their size, morphology, and corticosterone secretion.
This article has been cited by other articles:
 |
|
 |
|
  J. M. C. Connell, S. M. MacKenzie, E. M. Freel, R. Fraser, and E. Davies A Lifetime of Aldosterone Excess: Long-Term Consequences of Altered Regulation of Aldosterone Production for Cardiovascular Function Endocr. Rev., April 1, 2008; 29(2): 133 - 154. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Janes, K. M. E. Chu, A. J. L. Clark, and P. J. King Mechanisms of Adrenocorticotropin-Induced Activation of Extracellularly Regulated Kinase 1/2 Mitogen-Activated Protein Kinase in the Human H295R Adrenal Cell Line Endocrinology, April 1, 2008; 149(4): 1898 - 1905. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J Manolopoulou, M Bielohuby, S J Caton, C E Gomez-Sanchez, I Renner-Mueller, E Wolf, U D Lichtenauer, F Beuschlein, A Hoeflich, and M Bidlingmaier A highly sensitive immunofluorometric assay for the measurement of aldosterone in small sample volumes: validation in mouse serum J. Endocrinol., February 1, 2008; 196(2): 215 - 224. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-B. Linhart and J. A. Majzoub Pomc Knockout Mice Have Secondary Hyperaldosteronism Despite an Absence of Adrenocorticotropin Endocrinology, February 1, 2008; 149(2): 681 - 686. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Tolle and M. J. Low In Vivo Evidence for Inverse Agonism of Agouti-Related Peptide in the Central Nervous System of Proopiomelanocortin-Deficient Mice Diabetes, January 1, 2008; 57(1): 86 - 94. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Chida, S. Nakagawa, S. Nagai, H. Sagara, H. Katsumata, T. Imaki, H. Suzuki, F. Mitani, T. Ogishima, C. Shimizu, et al. Melanocortin 2 receptor is required for adrenal gland development, steroidogenesis, and neonatal gluconeogenesis PNAS, November 13, 2007; 104(46): 18205 - 18210. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Michailidou, A. P Coll, C. J Kenyon, N. M Morton, S. O'Rahilly, J. R Seckl, and K. E Chapman Peripheral mechanisms contributing to the glucocorticoid hypersensitivity in proopiomelanocortin null mice treated with corticosterone J. Endocrinol., July 1, 2007; 194(1): 161 - 170. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Davies, S. Omer, J. C. Buckingham, J. F. Morris, and H. C. Christian Expression and Externalization of Annexin 1 in the Adrenal Gland: Structure and Function of the Adrenal Gland in Annexin 1-Null Mutant Mice Endocrinology, March 1, 2007; 148(3): 1030 - 1038. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. T. To, S. Hahner, G. Nica, K. B. Rohr, M. Hammerschmidt, C. Winkler, and B. Allolio Pituitary-Interrenal Interaction in Zebrafish Interrenal Organ Development Mol. Endocrinol., February 1, 2007; 21(2): 472 - 485. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Smart, V. Tolle, V. Otero-Corchon, and M. J. Low Central Dysregulation of the Hypothalamic-Pituitary-Adrenal Axis in Neuron-Specific Proopiomelanocortin-Deficient Mice Endocrinology, February 1, 2007; 148(2): 647 - 659. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. P Coll, M. Fassnacht, S. Klammer, S. Hahner, D. M Schulte, S. Piper, Y C L. Tung, B. G Challis, Y. Weinstein, B. Allolio, et al. Peripheral administration of the N-terminal pro-opiomelanocortin fragment 1-28 to Pomc-/- mice reduces food intake and weight but does not affect adrenal growth or corticosterone production. J. Endocrinol., August 1, 2006; 190(2): 515 - 525. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Lee, L. R. Giles, W. L. Bryden, J. A. Downing, D. C. Collins, and P. C. Wynn The effect of active immunization against adrenocorticotropic hormone on cortisol, {beta}-endorphin, vocalization, and growth in pigs J Anim Sci, October 1, 2005; 83(10): 2372 - 2379. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Zwermann, D. M Schulte, M. Reincke, and F. Beuschlein ACTH 1-24 inhibits proliferation of adrenocortical tumors in vivo Eur. J. Endocrinol., September 1, 2005; 153(3): 435 - 444. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Su, L. C. Carey, N. K. Valego, and J. C. Rose Developmental Changes in Adrenocorticotrophin (ACTH)-Induced Expression of ACTH Receptor and Steroid Acute Regulatory Protein mRNA in Ovine Fetal Adrenal Cells Reproductive Sciences, September 1, 2005; 12(6): 416 - 420. [Abstract] [PDF]
|
|
|
|
|
|
A. P. Coll, B. G. Challis, M. Lopez, S. Piper, G. S.H. Yeo, and S. O'Rahilly Proopiomelanocortin-Deficient Mice Are Hypersensitive to the Adverse Metabolic Effects of Glucocorticoids Diabetes, August 1, 2005; 54(8): 2269 - 2276. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. K. Valego, Y. Su, L. C. Carey, S. F. Young, S. B. Tatter, J. Wang, and J. C. Rose Hypothalamic-pituitary disconnection in fetal sheep blocks the peripartum increases in adrenal responsiveness and adrenal ACTH receptor expression Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2005; 289(2): R410 - R417. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M C Connell and E. Davies The new biology of aldosterone J. Endocrinol., July 1, 2005; 186(1): 1 - 20. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Karpac, D. Ostwald, S. Bui, P. Hunnewell, M. Shankar, and U. Hochgeschwender Development, Maintenance, and Function of the Adrenal Gland in Early Postnatal Proopiomelanocortin-Null Mutant Mice Endocrinology, June 1, 2005; 146(6): 2555 - 2562. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. D. Hammer, K. L. Parker, and B. P. Schimmer Minireview: Transcriptional Regulation of Adrenocortical Development Endocrinology, March 1, 2005; 146(3): 1018 - 1024. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
