Dynamics of hormone levels and immune activity in sheep during fasting, subsequent immobilization and the recovery period

Penka Moneva; Ivan Yanchev; Marina Tsaneva; Krasimir Velikov; Dimitar Gudev

Penka Moneva

, Ivan Yanchev

, Marina Tsaneva, Krasimir Velikov

, Dimitar Gudev

Abstract: The object of this study was to investigate endocrine and immune responses during the four-day fast, subsequent immobilization and the recovery period in ewes. One-hundred Ile de France ewes were allocated into two groups (n=14) according to their baseline hematocrit level: group I – low hematocrit, group II – high hematocrit level. А third (n=10) control group was included, whose animals did not fast but were also stressed by immobilization. The effect of fasting in sheep with low and high hematocrit was examined via 4 days fasting, followed by 30 minutes of immobilization. The following parameters were measured: cortisol, growth hormone, T3, T4, estradiol-17β, N/L ratio, reticulocytes (%). Immediately before the beginning and after the end of fasting, as well as on the 7th and 20th day after fasting, the weight of the animals was recorded. Blood samples were taken via jugular venepunction before the fasting (baseline level), at 24 h of fasting, after 4 days of fasting before immobilization, immediately after immobilization, during recovery period - at d7 and d20 after fasting.
The results allow the following conclusions to be drawn: Stress exerts a specific tissue activity that, at normal levels of cortisol (in order to conserve energy), activates the immune defense by using specific mechanisms (most likely activation of 11 beta-hydroxy-steroid dehydrogenase of leukocytes) allowing activation of the inactive cortisol and realizing the redistributing effect of cortisol by binding to the leukocytes glucocorticoid receptors. The unchanged level of T3 under fasting conditions confirms our hypothesis of tissue-specific activity, because increased lipolysis during fasting is most likely associated with an increased level of reversible T3 at an unchanged level of total T3, which allows, with unchanged metabolic activity, to carry out the specific activating effect of T3 on lipid metabolism Growth hormone, like other hormones, most likely also carries out tissue-specific activity, allowing activation of lipolytic activity at unchanged growth hormone values. A directly proportional relationship between growth hormone level and hematocrit level was found, which is probably related to the stimulating effect of growth hormone on erythropoietin. An inverse relationship between T3 and growth intensity was established. The data allow us to assert that when a hormone has several biological effects and the maintenance of homeostasis in a certain stressful situation requires the suppression of one of the biological effects of the hormone and the stimulation of another, specific tissue mechanisms are used that allow the activation of a certain function against unchanged hormone level in the body.

Keywords: cortisol; fasting; GH; N/L ratio; sheep; stress; T3; T4

Citation: Moneva, P., Yanchev, I., Tsaneva, M., Velikov, K. & Gudev, D. (2025). Dynamics of hormone levels and immune activity in sheep during fasting, subsequent immobilization and the recovery period. Bulg. J. Agric. Sci., 31(3), 585–594.

References: (click to open/close)

Aris, J. P., Alvers, A. L., Ferraiuolo, R. A., Fishwick, L. K., Hanvivatpong, A., Hu, D., Kirlew, C., Leonard, M.T., Losin, K. J., Marraffini, M., Seo, A. Y., Swanberg, V., Westcott, J. L., Wood, M. S., Leeuwenburgh, C. & Dunn Jr., W. A. (2013). Autophagy and leucine promote chronological longevity and respiration proficiency during calorie restriction in yeast. Experimental Gerontology, 48(10), 1107–1119.
Cignarella, F., Cantoni, C., Ghezzi, L., Salter, A., Dorsett, Y., Chen, L., Fontana, L., Weinstock, G. M., Cross, A. H., Zhou, Y. & Piccio, L. (2018). Intermittent fasting confers protection in CNS autoimmunity by altering the gut microbiota. Cell Metab., 27(6),1222–35.
Crane, C., Akhter, N., Johnson, B. W., Iruthayanathan, M., Syed, F., Kudo, A., Zhou, Y. H., & Childs, G. V. (2007). Fasting and glucose effects on pituitary leptin expression: is leptin a local signal for nutrient status? J. Histochem. Cytochem., 55(10), 1059–1073.
Davis, A. K., Maney, D. L. & Maerz, J. C. (2008). The use of leukocyte profiles to measure stress in vertebrates: a review for ecologists. Funct. Ecol., 22(5), 760–772.
Devesa, J., Almengló, C. & Devesa, P. (2016). Multiple effects of growth hormone in the body: is it really the hormone for growth? Clinical Medicine Insights Endocrinology and Diabetes, 9, 47–71.
Dhabhar, F. S. (2002). Stress-induced augmentation of immune function – the role of stress hormones, leukocyte trafficking, and cytokines. Brain, Behavior and Immunity, 16(6), 785–798.
Dhabhar, F. S., Malarkey, W. B., Neri, E. & McEwen, B. S. (2012). Stress-induced redistribution of immune cells-from barracks to boulevards to battlefields: a tale of three hormones-Curt Richter Award winner. Psychoneuroendocrinology, 37(9), 1345–1368.
Di Francesco, A., Di Germanio, C., Bernier, M. & De Cabo, R. (2018). A time to fast. Science, 362(6416), 770–775.
Fazeli, P. K., Misra, M., Goldstein, M., Miller, K.K. & Klibanski, A. (2010). Fibroblast growth factor-21 may mediate growth hormone resistance in anorexia nervosa. J. Clin. Endocrinol. Metab., 95(1), 369-374.
Gahete, M. D., Córdoba-Chacón, J., Luque, R. M. & Kineman, R. D. (2013). The rise in growth hormone during starvation does not serve to maintain glucose levels or lean mass but is required for appropriate adipose tissue response in female mice. Endocrinology, 154(1), 263–269.
Goodrick, C. L., Ingram, D. K., Reynolds, M. A., Freeman, J. R. & Cider, N. (1990). Effects of intermittent feeding upon body weight and lifespan in inbred mice: interaction of genotype and age. Mechanisms of Ageing and Devevelopment, 55(1), 69–87.
Hickman, D. L. (2017). Evaluation of the neutrophil: lymphocyte ratio as an indicator of chronic distress in the laboratory mouse. Lab. Anim. (NY), 46(7), 303–307.
Hua, K. M., Hodgkinson, S. C. & Bass, J. J. (1995). Differential regulation of plasma levels of insulin-like growth factors-II and –I by nutrition, age and growth hormone treatment in sheep. Journal of Endocrinology, 147(3), 507–516.
Ibrishimov, N. & Lalov, H. (1984). Clinical and laboratory investigations in veterinary medicine. Publisher “Zemizdat”, Sofia, 231 (Bg).
Inagaki, T., Lin, V. Y., Goetz, R., Mohammadi, M., Mangelsdorf, D. J. & Kliewer, S. A. (2008). Inhibition of growth hormone signaling by the fasting-induced hormone FGF21. Cell Metab., 8(1), 77–83.
Jabbar, A., Chang, W.-K., Dryden, G. W. & McClave, S. A. (2003). Gut immunology and the differential response to feeding and starvation. Nutr. Clin. Pract., 18(6), 461–482.
Kim, B. H., Joo, Y., Kim, M.-S., Choe, H. K., Tong, Q. & Kwon, O. (2021). Effects of intermittent fasting on the circulating levels and circadian rhythms of hormones. Endocrinol. Metab., (Seoul), 36(4), 745–756.
Longo, V. D. & Mattson, M. P. (2014). Fasting: molecular mechanisms and clinical applications. Cell. Metab., 19(2), 181–192.
Mendelsohn, A. R. & Larrick, J. W. (2014). Prolonged fasting/refeeding promotes hematopoietic stem cell regeneration and rejuvenation Rejuvenation Research, 17(4), 385–389.
Mesnage, R., Grundler, F., Schwiertz, A., Le Maho, Y. & de Toledo, F. W. (2019). Changes in human gut microbiota composition are linked to the energy metabolic switch during 10 d of Buchinger fasting. Journal of Nutritional Science, 8, e36, 1–14.
Moller, L., Dalman, L., Norrelund, H., Billestrup, N., Frystyk, J., Moller, N. & Jorgensen, J. O. (2009). Impact of fasting on growth hormone signaling and action in muscle and fat. J. Clin. Endocrinol. Metab.,94(3), 965–972.
Moneva, P., Yanchev, I., Dyavolova, M. & Gudev, D. (2019). Discrepancy between plasma cortisol level and neutrophil-to-lymphocyte ratio in sheep during shearing. Bulg. J. Agric. Sci., 25(3), 564–569.
Nakamura, Y., Walker, B. R. & Ikuta, T. (2016) Systematic review and meta-analysis reveals acutely elevated plasma cortisol following fasting but not less severe calorie restriction. Stress, 19(2), 151–157.
Redman, L. M., Smith, S. R., Burton, J. H., Martin, C. K., Ilyasova, D. & Ravussin, E. (2018). Metabolic slowing and reduced oxidative damage with sustained caloric restriction support the rate of living and oxidative damage. Theories of Aging Cell Metabоlism, 27(4), 805–815.
Spaulding, S. W., Chopra, I. J., Sherwin, R. S. & Lyall, S. S. (1976). Effect of caloric restriction and dietary composition on serum T3 and reverse T3 in man. The J. Clin. Endocrinol. Metab., 42(1),197-200.
Takakuwa, T., Nakashima, Y., Koh, H., Nakane, T., Nakamae, H. & Hino, M. (2019). Short-term fasting induces cell cycle arrest in immature hematopoietic cells and increases the number of naïve t cells in the bone marrow of mice. Acta Haematol., 141(3), 189-198.
Thaiss, C. A., Zmora, N., Levy, M. & Elian, E. (2016). The microbiome and innate immunity. Nature, 535(7610), 65–74.
Trepanowski, J. F. & Bloomer, R. J. (2010). The impact of religious fasting on human health. Nutrition Journal, 9(57), 1–9.
Vagenakis, A., Burger, A., Portnay, G., Rudolph, M., O'Brain, J., Azizi, F., Arky, R., Nicod, P., Ingbar, S. & Braverman, L. (1975). Diversion of peripheral thyroxine metabolism from activating to inactivating pathways during complete fasting. The J. Clin. Endocrinol. Metab., 41(1), 191-194.
Venegas-Borsellino, C. & Martindale, R. G. (2018). From religion to secularism: the benefits of fasting. Current Nutrition Report, 19, 131–138.

Date published: 2025-06-24

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