This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Spinedi, E. Articles by Gaillard, R. C. Search for Related Content PubMed PubMed Citation Articles by Spinedi, E. Articles by Gaillard, R. C.

A Regulatory Loop Between the Hypothalamo-Pituitary-Adrenal (HPA) Axis and Circulating Leptin: A Physiological Role of ACTH

Neuroendocrine Unit (E.S.), IMBICE, 1900 La Plata, Argentina; and Division of Endocrinology, Diabetology and Metabolism (E.S., R.C.G.), University Hospital, CH 1011 Lausanne, Switzerland

Address all correspondence and requests for reprints to: Eduardo Spinedi, Ph.D., IMBICE (CIC-CONICET), Calle 526 e/10 y 11, Neuroendocrine Unit, P.O. Box 403, La Plata 1900, Argentina.

The product of the ob/ob gene, leptin, is known to be able to exert a modulatory role on HPA axis function. The aim of the present study was to determine whether endogenous ACTH and glucocorticoids exert any regulatory effect on leptin secretion. For this purpose bilaterally adrenalectomized (ADX) or sham operated (Sham) adult male rats were implanted with an indwelling i.v. catheter. A subgroup of ADX animals received, at the same time of surgery, a s.c. corticosterone (B) pellet (75 mg) (ADX + B). All animals were subjected to experimental designs 7 days after surgery. Our results indicate, as expected, that 7-day ADX animals have several fold increased basal ACTH plamsa levels and non detectable circulating B, whereas ADX + B rats showed basal plasma ACTH levels in the range of Sham values and plasma B concentrations of about 5 µg/dl. Interestingly, basal plasma leptin levels were significantly (P < 0.05) decreased by 7 days post ADX, and B replacement therapy (ADX + B) restored circulating leptin to Sham levels. Acute dexamethasone (Dxm; 30 µg/kg body weight, i.v.) treatment induced a very rapid decrease in plasma ACTH concentrations in both Sham and ADX rats, as well as a decrease in plasma B levels in Sham rats. Interestingly, Dxm test had no effect on plasma leptin levels in Sham animals; however, in ADX rats, the synthetic glucocorticoid increased plasma leptin concentrations, restoring the levels observed in Sham rats. This effect occurred at the same time when plasma ACTH levels were decreasing toward basal Sham values. These results clearly indicate that, beside the known effects of leptin on HPA axis function, circulating ACTH and glucocorticoid are able to modulate leptin secretion in plasma. The lack of circulating glucocorticoid and/or increased plasma ACTH concentrations, are responsible for decreasing leptin output, whereas decreased plasma ACTH concentrations allow an increase of leptin secretion in blood. Our data strongly support the existence of a closed, bi-directional, circuit between HPA axis function and adipose tissue metabolism. They further indicate the physiological relevance of different types of stress associated with many phenotypes of obesity.

This article has been cited by other articles:

				M. T. Foster, J. P. Warne, A. B. Ginsberg, H. F. Horneman, N. C. Pecoraro, S. F. Akana, and M. F. Dallman Palatable Foods, Stress, and Energy Stores Sculpt Corticotropin-Releasing Factor, Adrenocorticotropin, and Corticosterone Concentrations after Restraint Endocrinology, May 1, 2009; 150(5): 2325 - 2333. [Abstract] [Full Text] [PDF]

				J. Gay, E. Kokkotou, M. O'Brien, C. Pothoulakis, and K. P. Karalis Corticotropin-Releasing Hormone Deficiency Is Associated with Reduced Local Inflammation in a Mouse Model of Experimental Colitis Endocrinology, July 1, 2008; 149(7): 3403 - 3409. [Abstract] [Full Text] [PDF]

				H. Muller, N. Schweitzer, O. Johren, P. Dominiak, and W. Raasch Angiotensin II stimulates the reactivity of the pituitary-adrenal axis in leptin-resistant Zucker rats, thereby influencing the glucose utilization Am J Physiol Endocrinol Metab, September 1, 2007; 293(3): E802 - E810. [Abstract] [Full Text] [PDF]

				E. D Bruder, L. Jacobson, and H. Raff Plasma leptin and ghrelin in the neonatal rat: interaction of dexamethasone and hypoxia J. Endocrinol., June 1, 2005; 185(3): 477 - 484. [Abstract] [Full Text] [PDF]

				G. Mazzocchi, P. Rebuffat, A. Ziolkowska, G. P. Rossi, L. K. Malendowicz, and G. G. Nussdorfer G Protein Receptors 7 and 8 Are Expressed in Human Adrenocortical Cells, and Their Endogenous Ligands Neuropeptides B and W Enhance Cortisol Secretion by Activating Adenylate Cyclase- and Phospholipase C-Dependent Signaling Cascades J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3466 - 3471. [Abstract] [Full Text] [PDF]

				J. R. Levy and W. Stevens Plasma hyperosmolality stimulates leptin secretion acutely by a vasopressin-adrenal mechanism Am J Physiol Endocrinol Metab, August 1, 2004; 287(2): E263 - E268. [Abstract] [Full Text] [PDF]

				G. Mazzocchi, L. K. Malendowicz, F. Aragona, R. Spinazzi, and G. G. Nussdorfer Cholecystokinin (CCK) Stimulates Aldosterone Secretion from Human Adrenocortical Cells via CCK2 Receptors Coupled to the Adenylate Cyclase/Protein Kinase A Signaling Cascade J. Clin. Endocrinol. Metab., March 1, 2004; 89(3): 1277 - 1284. [Abstract] [Full Text] [PDF]

				S.-C. Liao, M.-B. Lee, Y.-J. Lee, and T.-S. Huang Hyperleptinemia in Subjects With Persistent Partial Posttraumatic Stress Disorder After a Major Earthquake Psychosom Med, January 1, 2004; 66(1): 23 - 28. [Abstract] [Full Text] [PDF]

				Y. Ueta, Y. Ozaki, J. Saito, and T. Onaka Involvement of Novel Feeding-Related Peptides in Neuroendocrine Response to Stress Experimental Biology and Medicine, November 1, 2003; 228(10): 1168 - 1174. [Abstract] [Full Text] [PDF]

				M. E. Gemmill, R. L. Eskay, N. L. Hall, L. W. Douglass, and T. W. Castonguay Leptin Suppresses Food Intake and Body Weight in Corticosterone-Replaced Adrenalectomized Rats J. Nutr., February 1, 2003; 133(2): 504 - 509. [Abstract] [Full Text] [PDF]

				M. Friedberg, E. Zoumakis, N. Hiroi, T. Bader, G. P. Chrousos, and Z.'e. Hochberg Modulation of 11{beta}-Hydroxysteroid Dehydrogenase Type 1 in Mature Human Subcutaneous Adipocytes by Hypothalamic Messengers J. Clin. Endocrinol. Metab., January 1, 2003; 88(1): 385 - 393. [Abstract] [Full Text] [PDF]

				R. FAGGIONI, K. R. FEINGOLD, and C. GRUNFELD Leptin regulation of the immune response and the immunodeficiency of malnutrition FASEB J, December 1, 2001; 15(14): 2565 - 2571. [Abstract] [Full Text] [PDF]

				K. Proulx, S. Clavel, G. Nault, D. Richard, and C.-D. Walker High Neonatal Leptin Exposure Enhances Brain GR Expression and Feedback Efficacy on the Adrenocortical Axis of Developing Rats Endocrinology, November 1, 2001; 142(11): 4607 - 4616. [Abstract] [Full Text] [PDF]

				K. Arvaniti, D. Richard, F. Picard, and Y. Deshaies Lipid deposition in rats centrally infused with leptin in the presence or absence of corticosterone Am J Physiol Endocrinol Metab, October 1, 2001; 281(4): E809 - E816. [Abstract] [Full Text] [PDF]

				N. Cherradi, A. M. Capponi, R. C. Gaillard, and F. P. Pralong Decreased Expression of Steroidogenic Acute Regulatory Protein: A Novel Mechanism Participating in the Leptin-Induced Inhibition of Glucocorticoid Biosynthesis Endocrinology, August 1, 2001; 142(8): 3302 - 3308. [Abstract] [Full Text] [PDF]

				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]

				G. Mazzocchi, L. K. Malendowicz, L. Gottardo, F. Aragona, and G. G. Nussdorfer Orexin A Stimulates Cortisol Secretion from Human Adrenocortical Cells through Activation of the Adenylate Cyclase-Dependent Signaling Cascade J. Clin. Endocrinol. Metab., February 1, 2001; 86(2): 778 - 782. [Abstract] [Full Text]

				P. Chiodera, R. Volpi, L. Capretti, S. Cataldo, G. Speroni, and V. Coiro Effect of Systemic Oxytocin Administration on Dexamethasone-Induced Leptin Secretion in Normal and Obese Men J. Clin. Endocrinol. Metab., October 1, 2000; 85(10): 3683 - 3686. [Abstract] [Full Text]

				R. Faggioni, A. Moser, K. R. Feingold, and C. Grunfeld Reduced Leptin Levels in Starvation Increase Susceptibility to Endotoxic Shock Am. J. Pathol., May 1, 2000; 156(5): 1781 - 1787. [Abstract] [Full Text] [PDF]

				J. Iqbal, S. Pompolo, R. V. Considine, and I. J. Clarke Localization of Leptin Receptor-Like Immunoreactivity in the Corticotropes, Somatotropes, and Gonadotropes in the Ovine Anterior Pituitary Endocrinology, April 1, 2000; 141(4): 1515 - 1520. [Abstract] [Full Text] [PDF]

				M. Renz, E. Tomlinson, B. Hultgren, N. Levin, Q. Gu, R. A. Shimkets, D. A. Lewin, and T. A. Stewart Quantitative Expression Analysis of Genes Regulated by Both Obesity and Leptin Reveals a Regulatory Loop between Leptin and Pituitary-derived ACTH J. Biol. Chem., March 31, 2000; 275(14): 10429 - 10436. [Abstract] [Full Text] [PDF]

				Z. N. Kain, Z. Zimolo, and G. Heninger Leptin and the Perioperative Neuroendocrinological Stress Response J. Clin. Endocrinol. Metab., July 1, 1999; 84(7): 2438 - 2442. [Abstract] [Full Text]