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I. INTRODUCTION ALTHOUGH it is almost thirty years since abnormalities of blood cholesterol content were observed to follow deranged thyroid activity (1), the mechanism responsible for these changes remains unknown. Moreover, the obscurity surrounding this interesting thyroid-blood cholesterol relationship has persisted, despite the clinical recognition (2) of a possible association between the hypercholesteremia of the hypothyroid state and the premature atherosclerosis believed by many to occur in this disease. It appeared important to investigate some of the underlying processes concerned with the altered blood cholesterol level in both the hyperthyroid and hypothyroid states. By using various new techniques we have been able to discover that the underlying fault in cholesterol metabolism in the hyperthyroid state is one in which an increase occurs, not only in the rate of manufacture, but also in the rate of excretion and destruction of cholesterol. We have also found that, conversely, the same proces...

IT HAS been abundantly demonstrated that the liver rapidly metabolizes hydrocortisone (compound F) both in vivo and in vitro (1–8). Alterations are effected both in the side chain at C17 and in saturation of double bonds in ring A. Bile has been demonstrated to be an excretory pathway for metabolites of hydrocortisone, but the nature of these substances in bile has not been clearly characterized (8, 9). The work reported here represents data gathered by a study of this problem in the isolated perfused rat liver. MATERIALS AND METHODS A perfusion apparatus for the isolated rat liver was employed which has been described in detail in previous publications (10, 11). Hydrocortisone was determined in plasma by the Silber-Porter method (12). Hydrocortisone was determined in bile by the same chloroform extraction as used in dealing with plasma. When H2SO4 was added however, a cherry-red interfering substance developed in both the blank (extract plus H2SO4) and the sample (extract plus phenylhydrazine plus H2SO4)...

Administration of either a lyophilized or gel preparation of corticotropin in sufficient amounts is capable of lowering the fasting and postprandial elevation of the plasma triglyceride of the hyperlipemic as well as the normolipemic subject, regardless of whether the subject exhibits a behavior pattern of the A or B type. This hypolipemic effect of the corticotropin preparation was not found to be due to its possible lipotropin or growth hormone content. On the basis of these results, it is concluded that corticotropin can serve as a hypolipemic agent in man. The administration of a specially prepared and essentially pure corticotropin replicated the hypolipemic effects of the commercial preparation of ACTH. Administration also of either hydrocortisone or epinephrine failed to effect the hypolipemic influence observed after injection of corticotropin.

DESPITE the profound influence of thyroid activity upon cholesterol metabolism (Rosenman, Friedman and Byers, 1951, 1952; Friedman, Byers and Rosenman, 1952; Byers, Friedman, and Rosenman, in press), there is little evidence that similar influence is exerted by other endocrine glands. More recently, however, changes in serum cholesterol have been described following administration of adrenocorticotrophic and adrenocortical hormones (Conn, Vogel, Louis and Fajans, 1950; Adlersberg, SchaefTer and Drachman, 1950). It therefore was believed important to determine whether these and other hormones altered hepatic synthesis of cholesterol. Previous studies from this laboratory clearly have shown that the liver is the main source of the plasma cholesterol content (Friedman, Byers and Michaelis, 1951), and that the biliary concentration of cholesterol is a reliable index of the rate of hepatic synthesis of this substance (Byers and Friedman, 1952). Therefore, it is believed that studies of the effects of various s...