metallothionein and Endocrine-System-Diseases

The essentiality of zinc for humans was recognized in the early 1960s. The causes of zinc deficiency include malnutrition, alcoholism, malabsorption, extensive burns, chronic debilitating disorders, chronic renal disease, certain diuretics, the use of chelating agents such as penicillamine for Wilson's disease, and genetic disorders such as acrodermatitis enteropathica and sickle cell disease. The requirement of zinc is increased in pregnancy and during the growing age period. The clinical manifestations in severe cases of zinc deficiency included bullous-pustular dermatitis, alopecia, diarrhoea, emotional disorder, weight loss, intercurrent infections, hypogonadism in males and it is fatal if untreated. A moderate deficiency of zinc is characterized by growth retardation and delayed puberty in adolescents, hypogonadism in males, rough skin, poor appetite, mental lethargy, delayed wound healing, taste abnormalities and abnormal dark adaptation. In mild cases of zinc deficiency in human subjects, we have observed oligospermia, slight weight loss and hyperammonaemia. Zinc is a growth factor. As a result of its deficiency, growth is affected adversely in many animal species and in man. Inasmuch as zinc is needed for protein and DNA synthesis and cell division, it is believed that the growth effect of zinc is related to its effect on protein synthesis. Testicular functions are affected adversely as a result of zinc deficiency in both humans and experimental animals. This effect of zinc is at the end organ level and the hypothalamic--pituitary axis is intact in zinc-deficient subjects. Inasmuch as zinc is intimately involved in a cell division, its deficiency may adversely affect testicular size and thus its function. In mice, the incidence of degenerate oocytes, and hypohaploidy and hyperhaploidy in metaphase II oocytes were increased due to zinc deficiency. Zinc at physiological concentrations reduced prolactin secretion from the pituitary in vitro and it has been suggested that this trace element may have a role in the in vivo regulation of prolactin release. Thymopoietin, a hormone needed for T-cell maturation, has also been shown to be zinc dependent. It is clear that zinc may have several roles in biochemical and hormonal functions of various endocrine organs. Future research in this area is very much needed.

Topics: Adrenal Gland Diseases; Animals; Biological Availability; Cell Membrane; Endocrine System Diseases; Enzymes; Ethanol; Female; Gastrointestinal Diseases; Glucose; Gonads; Humans; Immunity; Metallothionein; Nucleic Acids; Nutritional Physiological Phenomena; Pregnancy; Pregnancy Complications; Prolactin; Thymopoietins; Thyroid Diseases; Wound Healing; Zinc

Northern blot analysis was used to investigate the effect of dexamethasone (Dex) or zinc on messenger RNA (mRNA) levels of metallothionein-IIa (MT-IIa) in fibroblasts from a patient with cortisol hyperreactive syndrome and from three normal subjects. Dex was seen to increase MT-IIa mRNA levels and brought them to a maximum after 12 h. Zinc also increased the levels of MT-IIa mRNA and brought them to a maximum at 8 h after the addition. Dex as well as zinc caused a dose-related increase in MT-IIa mRNA levels. Dex had a maximal inductive effect on MT-IIa at a concentration of 10(-6) mol/L and zinc at a concentration of 10(-4) mol/L. There was no significant difference in the levels of basal expression of the MT-IIa gene between the patient's and normal fibroblasts. But in three separate experiments induction of MT-IIa gene by Dex obtained for the patient's fibroblasts was almost twice as much as that for normal fibroblasts. On the other hand, there were no significant difference in induction by zinc between the patient's and normal fibroblasts. These data indicated that the patient's cells were hyperreactive to glucocorticoids as seen from the effect of Dex on the MT-IIa mRNA levels.

Topics: Adrenal Glands; Cycloheximide; Dexamethasone; Endocrine System Diseases; Fibroblasts; Humans; Hydrocortisone; Kinetics; Metallothionein; RNA, Messenger; Syndrome; Zinc