Factors influencing serum copper and ceruloplasmin oxidative activity in the rat.

MEYER, B. J., A. C. MEYER AND M. K. HORWITT. Fuctovs zh$uencing serum copper and cevuloplasmin oxidative activity in the rat. Am. J. Physiol. 194(3): @I-584* 19.58. -The effect of turpentine, estradiol benzoate and epinephrine hydrochloride on the copper concentration and paraphenylenediamine oxidase activity of serum were studied in the male albino rat. All three of these substances raised the serum copper level and paraphenylenediamine oxidase activity in both ‘control’ and ‘adrenalectomized’ animals, turpentine being the most active. The average serum copper level is approximately the same for normal humans and rats, while the phenylenediamine oxidase activity of normal human serum is about 2-3 times as high as that of rat serum. The data are discussed with relation to the known facts about serum copper in normal subjects and mental patients. IETARY intake, tissue stores and exD cretory mechanisms are important in the regulation of serum copper concentration, but we know relatively little about the physiological control of these factors. In contrast with serum iron, the serum copper concentration is kept surprisingly constant in the normal animal and human being (1-3). In man, as well as in the albino rat, 95 % or more of the serum copper is bound to a protein, ceruloplasmin, which behaves like a. serum globulin (4, 5). In vitro, ceruloplasmin exhibits weak oxidative activity toward.s a variety of artificial substrates, including paraphenylenediamine (ppd), adrenaline, ascorbic acid and dopa (6, 7). However, apart from suggestive evidence, it has not been proven that ceruloplasmin has any enzymatic function in the in tat t organism. Even if we accept the hypothesis that it is an enzyme, we still know nothing about its normal substrate. Blood ceruloplasmin levels are highly sensitive to stress conditions (S-I I). There is evidence that the endocrines are intimately related to the control of the serum ceruloplasmin Received for publication December 12, 1957. l Supported by grants-in-aid from the Illinois Mental Health Fund and the National Institutes of Health (AI I 26). concentration. Females have a higher ceruloplasmin level than males (2), and during pregnancy this concentration increases (9, IO, 12). Recently it was reported that estrogen increased the serum copper concentration in human subjects (13) and hypercupremia has been noted in patients with Addison’s disease (8, 14). However, corticotropin and cortisone did not influence the hypercupremia produced by turpentine in intact rats (IS). It has been suggested that the plasma copper concentration depends upon the functional state of the thyroid gland, as thyrotoxicosis raises the blood copper level (8, 9). However, hypothyroidism is associated with normal plasma copper concentrations (8, 9, 16) and no significant correlation was noticed between serum copper concentration and basal metabolic rate (3, 16). This study is an attempt to determine whether the adrenals play a role in the control of the serum copper level.