<i>In vivo</i> and <i>in vitro</i> studies of thymulin in marginally zinc‐deficient mice

Dardenne, Mireille; Savino, Wilson; Wade, Sali; Kaiserlian, Dominique; Lemonnier, Daniel; Bach, Jean‐François

doi:10.1002/eji.1830140513

Cited by 62 publications

(30 citation statements)

References 15 publications

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“…Although we know of no previous reports on thymulin levels in rats, our find ings are consistent with studies in aged dogs, mice and humans [10,18,19]. Since serum levels of zinc were nor mal in our old and senescent rats the age-dependent fall of circulating thymulin in this species cannot be ascribed to zinc deficiency [20], This notion coupled to the fact that our old and senescent rats treated with GH and T4 showed an increase in maximum thymulin activity without a con comitant decrease in thymulin inhibitors suggests that our treatment stimulated thymulin activity mainly by raising the circulating levels of the peptide.…”

Section: Discussionsupporting

confidence: 79%

Effects of Growth Hormone and Thyroxine on Thymulin Secretion in Aging Rats

Goya

Sosa²,

Bevilacqua³

et al. 1993

Neuroendocrinology

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It is well-established that the activity of the endocrine thymus is under neuroendocrine control. In particular, growth hormone (GH) and thyroxine (T₄) have been shown to be capable of reconstituting thymus function in hormone-deficient animals. It was therefore of interest to assess the effect of combined administration of ovine GH (0.1 mg/100 g BW/day) and T₄ (10 µg/100 g BW/ day) on serum thymulin levels in young (5 months), old (21 months) and senescent (29-30 months) male Sprague-Dawley rats. Age-matched controls received 0.1 mg bovine serum albumin/100 g BW daily during the same period (14 days). Prolactin (Prl), GH, T₄ and triiodothyronine (T₃) were measured in serum by radioimmunoassay, whereas serum thymulin was determined by rosette bioassay. As expected, GH and T₄ were lower in the old and senescent controls whereas serum Prl displayed a slight age-related increase. No age changes were detected in serum T3. Hormone-treated animals showed supra-physiologic levels of both T4 and T3, but serum levels were comparable among the three treated age groups for each thyroid hormone. Endogenous GH levels were moderately elevated in the treated rats. In the control rats serum thymulin showed a marked reduction from 5 to 21 months of age but no further reduction was observed between 21 and 29-30 months. Hormone treatment induced a mean relative increase (% increase relative to age-matched controls) in serum thymulin of 44, 38 and 48% in young, old and senescent rats, respectively. Despite this stimulation, thymulin levels in the old and senescent treated groups were still significantly lower than the corresponding values in the young controls. It is concluded that (a) the activity of the endocrine thymus declines with age in male rats, and (b) in relative terms, aged rats possess a preserved capacity to increase thymulin secretion in response to combined administration of GH and T₄.

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Section: Discussionsupporting

confidence: 79%

Effects of Growth Hormone and Thyroxine on Thymulin Secretion in Aging Rats

Goya

Sosa²,

Bevilacqua³

et al. 1993

Neuroendocrinology

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“…Furthermore, decreased thymulin serum levels were reported in mice submitted to diets designed to trigger deficiency in zinc, iron, or vitamins (Dardenne et al, 1984;Kuvibidila et al, 1990;Chandra, 1992). At least regarding zinc deficiency, similar results were found in humans (Prasad et al, 1988).…”

Section: Decreased Thymic Endocrine Function In Malnourished Individualsmentioning

confidence: 52%

The thymus gland is a target in malnutrition

2002

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Malnutrition, secondary to deficiency in uptake of proteins, metal elements or vitamins, consistently results in changes in the thymus gland. The organ undergoes a severe atrophy due to apoptosis-induced thymocyte depletion, particularly affecting the immature CD4 þ CD8 þ cells, as well as a decrease in cell proliferation. Such a feature is apparently linked to a hormonal imbalance, involving decrease of leptin and consequent raise of glucocorticoid hormone levels in the serum. Interestingly, this picture can be reversed after appropriate diet rehabilitation. The thymic microenvironment is also affected in malnutrition: morphological changes in thymic epithelial cells were found, together with a decrease of thymic hormone production by these cells. Additionally, intrathymic contents of extracellular proteins, such as fibronectin, laminin and collagens, are increased in the thymuses from malnourished children. Conjointly, the bulk of data discussed herein clearly points to the notion that the thymus gland is a target in malnutrition. Nevertheless, further relevant information regarding the physiology of the thymus, including the cytokine=chemokine secretion as well as the positive and negative selection events driven by TCR=MHC-peptide interactions in malnutrition, remains to be defined. These are questions that need to be answered in order to have a better understanding of the immunodeficiency seen in malnourished individuals.

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“…Information gathered to date indicate that a 30-day period of suboptimal intake of zinc in the young adult mouse, which produced a 20 to 25% weight loss, reduced the thymus to a quarter normal size and depleted the lymphocytes and macrophages in the spleen 50 to 70% (399)(400)(401). Thymic atrophy, which is a benchmark of both zinc deficiency and protein-calorie deficiency, was also accompanied by loss in activity of thymulin, a thymic hormone dependent on zinc for function (402). Antibody-mediated responses to both T-cell dependent and Tcell independent antigens were reduced 50 to 70% as demonstrated by several labs (399)(400)(401).…”

Section: Neurological Function and Excessmentioning

confidence: 97%

Zinc: Health Effects and Research Priorities for the 1990s

Walsh¹,

Sandstead²,

Prasad³

et al. 1994

Environmental Health Perspectives

156

225

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This review critically summarizes the literature on the spectrum of health effects of zinc status, ranging from symptoms of zinc deficiency to excess exposure. Studies on zinc intake are reviewed in relation to optimum requirements as a function of age and sex. Current knowledge on the biochemical properties of zinc which are critical to the essential role of this metal in biological systems is summarized. Dietary and physiological factors influencing the bioavailability and utilization of zinc are considered with special attention to interactions with iron and copper status. The effects of zinc deficiency and toxicity are reviewed with respect to specific organs, immunological and reproductive function, and genotoxicity and carcinogenicity. Finally, key questions are identified where research is needed, such as the risks to human health of altered environmental distribution of zinc, assessment of zinc status in humans, effects of zinc status in relation to other essential metals on immune function, reproduction, neurological function, and the cardiovascular system, and mechanistic studies to further elucidate the biological effects of zinc at the molecular level. - There is considerable evidence that zinc deficiency in humans is a serious worldwide problem and outweighs the potential problem of accidental, self-imposed, or environmental exposure to zinc excess. Acute deficiency (1) and chronic deficiency (2) are well-known entities in human populations and are probably much more common than generally recognized. The importance of zinc for human health was first documented in 1963 (3) Telephone (617) (617) 638-4329. E-mail: ctwalsh~bu.edu renal disease, and other chronically debilitating diseases are now known to be predisposing factors for zinc deficiency in humans (4).Zinc deficiency is reflected in clinical syndromes which affect men and women of all ages and all socioeconomic and cultural classes in the United States. It is neither prevalent in any specific area of the United States nor associated with any specific or definitive biochemical marker, which can make its identification difficult and confusing. Its presence is manifested by a wide spectrum of symptoms, from acute, life threatening problems to mild subclinical or marginal disorders which may only vaguely disturb well being. The acute problems are often seen in profoundly ill patients treated in hospitals, whereas subclinical problems may be so vague that patients seek assistance outside traditional medical practice.Based upon clinical data and using traditional, epidemiologic techniques, Henkin and Aamodt (5) have reclassified zinc deficiency into three syndromes; these are a) acute, b) chronic, and c) subacute zinc deficiency. Acute zinc deficiency is relatively uncommon and follows parenteral hyperalimentation or oral L-histidine administration. Chronic zinc deficiency is more common, usually resulting from chronic dietary lack of zinc. Subacute or latent zinc deficiency is the most common of these syndromes. It is estimated that there are 4...

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In vivo and in vitro studies of thymulin in marginally zinc‐deficient mice

Cited by 62 publications

References 15 publications

Effects of Growth Hormone and Thyroxine on Thymulin Secretion in Aging Rats

Effects of Growth Hormone and Thyroxine on Thymulin Secretion in Aging Rats

The thymus gland is a target in malnutrition

Zinc: Health Effects and Research Priorities for the 1990s

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