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J Clin Endocrinol Metab. 2011 Nov;96(11):3416-23. doi: 10.1210/jc.2011-1665. Epub 2011 Aug 24.

Energy deprivation alters in a leptin- and cortisol-independent manner circulating levels of activin A and follistatin but not myostatin in healthy males.

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Division of Endocrinology, Diabetes, and Metabolism, Harvard Medical School and Harvard School of Public Health, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, Massachusetts 02215, USA.



Activin A, myostatin, and follistatin have recently emerged as important regulatory molecules of reproduction and the musculoskeletal system. Little is known, however, about their day/night patterns of secretion and their physiological regulation by energy availability.


The objective of the study was to explore day/night patterns of secretion and assess whether energy deprivation alters circulating levels of activin A, myostatin, follistatin, and cortisol and to examine whether leptin may mediate this effect. DESIGN, SETTING AND PATIENTS, AND INTERVENTIONS: Seven healthy lean men (aged 23.2 ± 3.7 yr, body mass index 23.6 ± 1.7 kg/m(2)) were studied for 72 h under three different conditions: on their baseline/isocaloric diet and in a complete fasting state with administration of either placebo or metreleptin. The two fasting studies were randomized and double blinded. Blood samples were obtained every 15 min from 0800 h on d 3 until 0800 h on d 4 and pooled hourly.


Serum concentrations of activin A, myostatin, follistatin, cortisol, and leptin were measured.


In contrast to cortisol, we demonstrated no day/night pattern of activin A, myostatin, and follistatin secretion. Activin A concentrations decreased significantly in response to energy deprivation (P < 0.01). Follistatin and cortisol concentrations increased significantly (P < 0.01 and P < 0.01, respectively). Myostatin remained unaffected (P = 0.40). Leptin administration reversed cortisol response (P < 0.01) but failed to alter activin A, follistatin, or myostatin concentrations.


Unlike cortisol, there is no day/night variation in the concentrations of activin A, myostatin, and follistatin in healthy young males. Although energy deprivation-induced cortisol changes are leptin mediated, the changes in follistatin and activin A concentrations occur through a leptin-independent pathway.

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