Plasma ACTH and 17-hydroxycorticosteroid concentrations were measured at various intervals in patients recovering from prolonged pituitary suppression. Pituitary-adrenal recovery was found to follow a definite pattern requiring several months for completion. Initially, both ACTH and corticosteroid levels were relatively low, a situation similar to that seen in patients with hypopituitarism. Thereafter, plasma ACTH levels gradually increased until they were supernormal, but there was a lag of several

The primary event following the administration of adrenocorticotropic hormone (ACTH) is the immediate increase in steroid synthesis by the adrenal gland.1 Previous studies by numerous investigators suggested that this action of ACTH was the result of specific activation of enzymes.2' 3 However, studies showing that puromycin or chloramphenicol blocked the stimulation of corticosterone synthesis by ACTH suggested that protein synthesis was involved in this process.4 5 But

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The first of the three volumes of this encyclopaedic dictionary of dermatology was reviewed in this Journal in April 1971. The second volume covers eczema, including occupational dermatoses, seborrhoea.

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The transfer of lipoprotein-bound cholesterol into adrenal cells was examined. Adrenal glands from unstimulated or corticotropin stimulated hypophysectomized rats were incubated with high density lipoprotein (HDL) or low density lipoprotein LDL containing radiolabeled cholesterol. The rate of transfer of labeled cholesterol from HDL into the glands was two to three times greater than from LDL. Corticotropin stimulation increased the transfer of cholesterol from HDL but not LDL. The effects of corticotropin were not dependent on subsequent cholesterol utilization for steroidogenesis. The process of cholesterol transfer from HDL was linear with time over 2 hr at 370 and greatly reduced at 40. In addition, the transfer process became saturated above an HDL cholesterol concentration of 900 sg/ml. About 25% of the labeled adrenal cholesterol arising from HDL was recovered within the mitochondria. The labeled cholesterol within isolated mitochondria could undergo mitochondrial conversion to pregnenolone. Finally, the delipidated HDL apolipoproteins, apoA-I and apoA-II, when added to incubations containing less than saturating concentrations of HDL, stimulated transfer of labeled cholesterol from HDL to adrenal cells. These studies suggest that rat adrenal tissue possesses an HDL specific hormonally-responsive mechanism for accumulating extracellular cholesterol and that apoA-I and apoA-II have a significant function in the uptake process.The mechanisms responsible for transferring cholesterol from plasma into cells are of particular interest because of their possible role in atherosclerotic disease. Adrenal tissue may serve as a useful model for studying these mechanisms because studies in man (1, 2) and the rat (3, 4) showed that 80% or more of the cholesterol substrate for adrenal steroidogenesis may come from plasma. However, little is known about the process by which extracellular cholesterol enters the adrenal cells. Dexter et al. (4) have observed that the uptake process is stimulated by corticotropin (adrenocorticotrophic hormone, ACTH), and furthermore that the stimulatory effect of ACTH persists even when utilization of accumulating cholesterol is blocked by specific inhibitors.Serum cholesterol is lipoprotein bound, predominantly by the high density lipoprotein (HDL) and low density lipoprotein (LDL) fractions. In the rat (5), 60% of the circulating cholesterol is found in HDL and 30% in LDL, while in man 30% and 60% are found in HDL and LDL, respectively (6). In order to better understand the uptake of cholesterol by adrenal cells as well as ACTH regulation of the uptake process, we have examined the ability of HDL and LDL to serve as substrate for transfer of cholesterol to the adrenal. The observations reported here suggest that HDL is the preferred substrate for adrenal cholesterol uptake, and that uptake from HDL is regulated by ACTH. Furthermore, these studies suggest that the HDL apoproteins, apoA-I and apoA-II, play a role in the cholesterol uptake process. Table legends. Incubations were p...

A B S T R A C T Properties of adenyl cyclase of normal adrenals and of a corticosterone-producing adrenal cancer of the rat have been compared. Enzyme activity was found in all particulate fractions of both tissues. The cyclase of the tumor as well as of the adrenals was stimulated by adrenocorticotropic hormone (ACTH) over similar concentration ranges. Unexpectedly, the tumor enzyme was also stimulated by epinephrine, norepinephrine, and thyroid-stimulating hormone (TSH). These hormones produced a dose-related effect over a concentration span that was comparable with that for ACTH. The tumor cyclase was not responsive to angiotensin II, vasopressin, glucagon, insulin, growth hormone, parathyroid hormone, and thyrocalcitonin. ACTH was the only hormonal preparation that stimulated normal adrenal cyclase. These findings are compatible either with the possibility that the adenyl cyclase receptor of the tumor has undergone structural alteration with a consequent loss of specificity for ACTH or with the possibility that the tumor possesses several cyclase regulatory receptors.

The role of ACTH in various clinical disorders has been difficult to ascertain because the available assay methods have lacked the sensitivity necessary for valid quantitation of the hormone in the plasma of normal subjects (1-4). Even the method of Lipscomb and Nelson (5), the most sensitive practical bioassay procedure now available, usually requires the injection of at least 0.05 mU of ACTH per rat, if responses are to be elicited that will be statistically significant without the use of a prohibitive number of animals. It is usually impractical to inject more than 5 ml of crude human plasma into a single rat. Therefore, in order to be accurately measurable by this procedure, the concentration of ACTH in the plasma must be at least 0.05 mU per 5 ml, or 1 mU per 100 ml.Numerous studies indicate that normal plasma levels of ACTH are well below this concentration. Byr the adrenal ascorbic acid depletion assay method, Sydnor, Sayers, Brown, and Tyler (1) were unable to detect ACTH in plasma of normal subjects, even after attempting to extract the hormone with oxvcellulose in preparation for the bioassay. These workers concluded that blood ACTH concentrations of normal human subjects were less than 0.5 mU per 100 ml. Using a similar procedure, Fujita (3) estimated the normal level of ACTH to be about 1 mU per L, i.e., 0.1 mU per 100 ml. Cooper and Nelson (6) were able to detect ACTH in the plasma of only 3 of 10 patients before surgery, by a method that they