I 202 HANDBOOK OF PHYSIOLOGY ^ CIRCULATION II 



that the primary effect on circulating lipids is due to 

 cortisone (31, 182). It has to be borne in mind, 

 however, that data derived on adrenalectomized 

 animals are complicated by the fact that simul- 

 taneously with the depletion of cortical hormones 

 there is also a lack of medullary catecholamines, and 

 these, too, have an effect on lipid metabolism. 



Aldosterone, the adrenal hormone affecting elec- 

 trolyte metabolism, apparentlv has no effect on the 

 circulating lipids, but may affect the vascular wall 

 according to some recent data (80). 



The pituitarv adrenocorticotropic hormone 

 (ACTH) has an effect similar to, but less marked than, 

 cortisone. In man, the administration of either corti- 

 sone or ACTH produces an initial depression of 

 serum cholesterol levels with a subsequent rise on 

 continued administration (144). In the dog, the 

 response of the serum lipids to corticosteroids, 

 particularly' cortisone, is relatively mild. In the rabbit 

 and the rat, the effects of ACTH and corticosteroids 

 are qualitatively similar but much more pronounced. 

 The serum cholesterol elevation resulting from corti- 

 sone treatment is especially marked in the free 

 cholesterol fraction. Phospholipids are elevated 

 concomitantly, resulting in a normal C/P ratio, 

 despite elevated cholesterol levels. Triglycerides are 

 also increased, rendering the serum lactescent (7). 

 In the chick, the active steroid is 1 7-hydroxycorti- 

 costerone (compound F). It has lipid effects similar 

 to those described in the rabbit for cortisone. 



Atherosclerosis has not been induced in dogs, 

 rabbits, or chicks by the administration of adrenal 

 cortical hormones despite the lipid changes they 

 produce. If these steroids are given in the presence of 

 an atherogenic diet, the effect on the circulating 

 lipids is variable depending upon the species, but 

 the effect on atherogenesis is similar — corticoids 

 depress cholesterol-induced atherogenesis. 



It has been postulated that the atherosclerosis- 

 depressing action of these steroids is due to their 

 decreasing the permeability of the vascular endo- 

 thelium. Adlersberg's group has shown that when 

 hyaluronidase — a substance which increases cell 

 permeability — is given simultaneously with cortisone 

 the atherosclerosis-inhibiting action of the corticos- 

 teroids is overcome and atherosclerosis proceeds as 

 in the controls (166). 



Some authors produced increased arteriosclerosis 

 and secondarily atherosclerosis by the administration 

 of ACTH in rats (171, 172) and dogs (100). It is 

 possible that these effects are due to the action of the 



hormone on the vascular ground substance (muco- 

 polysaccharides) and fibroblasts (102). 



No specific data are available implicating the 

 adrenal cortical hormones in blood coagulation or 

 clot lysis. 



adrenal medullary hormones. /-Epinephrine is 

 the adrenal medullary hormone most extensively 

 studied. It influences lipid metabolism and produces 

 damage of the vascular wall in the form of medial 

 necrosis and calcification. The other catecholamines 

 probably act in a similar manner. Both of these 

 actions of /-epinephrine may produce arterio- and 

 atherosclerosis. In addition, /-epinephrine, being a 

 pressor agent, may further increase atherogenesis due 

 to the arterial hvpertension which ensues on chronic 

 endogenous overproduction or by protracted exog- 

 enous administration of the hormone (126). 



In the older literature disparate data on the 

 circulating lipids after catecholamine administration 

 have been described. Some observers noted a transient 

 hyperlipemia, probably due to an action on mobiliza- 

 tion and transport (33, 45, 60, 71). Others observed a 

 decrease in serum cholesterol, phospholipid, and total 

 lipids (39, 71). Recently, Shafrir el a!. (143) clarified 

 some of these discrepancies. They showed that a single 

 subcutaneous injection of /-epinephrine in dogs 

 produces a prompt, transient elevation of serum-free 

 fatty acids and a delayed elevation of /i-lipoproteins. 

 Prolonged daily /-epinephrine administration, how- 

 ever, produced a marked increase in cholesterol 

 levels, with a smaller concomitant rise in phos- 

 pholipids. This epinephrine reaction was abolished by 

 adrenalectomy and restored by cortisone treatment. 



anterior pituitary hormones. Pituitary growth 

 hormone (somatotropin) influences lipid mobilization 

 and transport as well as the distribution of lipid 

 between the liver and fat depots (85). Information 

 on the influence of this hormone on circulating 

 serum lipids is scant and the effects are variable in 

 different species. However, this may be due, in part 

 at least, to the fact that there are differences, both 

 physiological and chemical, in the nature of growth 

 hormone preparations obtained from different animal 

 species (19). Some stimulation of fibroblast growth 

 with this hormone has been described (102). No data 

 are available indicating any possible effect of this 

 hormone on atherogenesis. 



Recently, Rudman et al. (134) demonstrated the 

 existence of a separate and distinct hyperlipemia- 

 producing hormone of the anterior pituitary. 



