Summary. A kinetic study of the conversion of blood cholesterol into hydrocortisone was carried out in two patients through prolonged infusions of cholesterol-4-14C. The following points appear to be established by our observations:1) The infused tracer behaved metabolically like endogenous cholesterol; it could therefore serve as a means of labeling plasma cholesterol for investigating its utilization by the adrenal cortex.2) At rest, about 80% of hydrocortisone derived from plasma cholesterol, the other 20% thus being synthesized in situ from acetate and other unlabeled precursors.3) Under ACTH stimulation the participation of plasma cholesterol in the synthesis of hydrocortisone was the same as at rest; the conversion of plasma cholesterol into hydrocortisone was thus proportional to the production of glucocorticosteroids by the adrenal glands.4) The specific activities of hydrocortisone allowed us to trace its adrenal precursors including adrenal cholesterol. The kinetics of the replacement of adrenal cholesterol by plasma cholesterol underlined the functional heterogeneity of the former. The experimental data were compatible with the following model: A fraction of plasma cholesterol entering the adrenal cell is immediately available for metabolism and conversion into steroid hormones, and another fraction turns over slowly, representing some form of storage.

This study reports the effects of the administration of pharmacologic doses of vitamin A on multiple parameters of thyroid function. Vitamin A decreased total T4 and T3 levels. With vitamin A treatment, there was a marked increase in the percentage dialyzable T3 and T4 both in vivo and in vitro. The serum-free T3 and T4 levels as measured by dialysis were on the whole normal in vitamin A-treated rats. Following thyroidectomy, the total T4 levels were still decreased, suggesting that vitamin A produced its effects by increasing peripheral clearance of thyroxine. Vitamin A did not alter basal thyroid stimulating hormone (TSH) or its response to thyroid releasing hormone, suggesting a relatively normal hypothalamic-pituitary-thyroid axis in vitamin A-treated animals. Vitamin A may decrease tissue responsiveness to thyroid hormones as evidenced by the tendency to decreased Na-K-ATPase activity in the livers from vitamin A-treated rats and the decreased growth hormone response to T3 in GH3 pituitary cultures as shown in this study and by the decreased basal metabolic rate found after vitamin A in previous studies. Vitamin A decreased thyroid gland size and increases 125I thyroid uptake. In vitro, vitamin A enhanced T4 to T3 conversion in hepatic homogenates.

A B S T R A C T The kinetics of plasma and adrenal cholesteral equilibration were analyzed in patients undergoing bilateral adrenalectomy for generalized mammary carcinoma. A biological model is proposed to help in the understanding of adrenal cholesterol physiology. It comprises two intracellular compartments: (1) A compartment of free adrenal cholesterol which is small (of the order of 17 mg) but turns over very fast; it is renewed approximately 8 times per day: 3 times by the inflow of free plasma cholesterol, and 5 times by the hydrolysis of esterified adrenal cholesterol, the contribution of adrenal cholesterol synthesis appearing to be relatively small. (2) A compartment of esterified adrenal cholesterol which is 20 times larger; it is constantly renewed by in situ esterification and hydrolysis with a daily fractional turnover rate of the order of 0.25. The direct and selective accumulation of plasma cholesteryl esters is practically absent. Only free adrenal cholesterol returns to plasma, mostly after conversion into steroid "hormones."However small the synthesis of adrenal cholesterol may be, it seems more important in the zona "reticularis." On the other hand, the inflow of plasma cholesterol and the turnover of the free adrenal compartment tend to be faster in the zona "fasciculata." The equilibration of plasma and adrenal cholesterol can proceed unmodified under conditions of ACTH suppression.

J Appl Physiol 28:42-49 (Jan) 1970 The equilibration of plasma and adrenal cholesterol was investigated during seven days after 14C-cholesterol admin¬ istration in 24 patients undergoing bilateral adrenalectomy for generalized mammary carcinoma. The specific activi¬ ties (SA) of free adrenal cholesterol increased very rapid¬ ly and tended toward those of free plasma cholesterol. They were higher than those for esterified plasma cho¬ lesterol during the first two days and followed the curve of total plasma cholesterol except for a constant mean

A study was made of changes induced by cholinergic agonists and antagonists in the K+, Na+, Ca2+ and Cl- content of saliva of 22 human subjects with denervated parotid salivary glands. At all stages after denervation there was an increased content of Na+ and Cl- in the secretion of the denervated gland as compared with that of the control glands: after administration of pilocarpine and carbacholine; after administration of a combination of atropine and pilocarpine; in 'paradoxical' salivation induced by atropine, scopolamine, metacine or chlorosyle; in spontaneous secretion; in reflex secretion when this was partially restored. The concentrations of Na+ and Cl- in the secretion of the denervated gland were disproportionately higher than would have been expected from the raised salivation rate. Secretions from the denervated glands by virtue of their increased content of Na+ and Cl- resembled so-called primary saliva. The increased output of Na+ and Cl- and high concentrations of these ions in the secondary saliva after denervation indicates that there is loss of the normal neural control over reabsorption of electrolytes in the epithelium of the glandular ducts. Further, that absence of this control results in disturbances of membrane ionic transport, of membrane permeability and of the metabolism of the gland.