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Search for other papers by T. H. SIMPSON in
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Search for other papers by R. S. WRIGHT in
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SUMMARY
The capacity of the interrenal tissue of the elasmobranch fish Squalus acanthias L., Scyliorhinus canicula L. and Galeus melastomus Rafinesque to synthesize corticosteroids in vitro has been examined and found to be augmented by the presence of NADPH or its generating system.
Homogenates of cold-stored interrenal tissue from all three species converted [4-14C]pregnenolone to labelled progesterone, corticosterone and 11-deoxycorticosterone. Homogenates from freshly killed S. canicula formed, additionally, 1α-hydroxycorticosterone. No indication of the synthesis of aldosterone, of 17α-hydroxycorticosteroids or of C19 steroids was obtained.
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SUMMARY
Corticotrophin (ACTH), hydrocortisone or prednisolone trimethylacetate were administered daily to sows from 24 hr. before oestrus or from day 14 of the cycle until the end of oestrus. Treatment beginning on day 14 delayed the peak in urinary oestrogen excretion normally seen, postponed the onset of oestrus by 1–3 days and shortened the duration of oestrus. Treatment begun before oestrus did not appear to alter the pattern of oestrogen excretion but shortened the duration of oestrus. Administration of ACTH, but not that of corticosteroids, also interfered with ovulation.
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Search for other papers by J. G. PHILLIPS in
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SUMMARY
Cyclical changes in the activity of adrenocortical tissue are a wellestablished phenomenon in many amphibian species but up to now they have been studied by observing changes in cytology or enzyme activity, e.g. steroid-3β-ol dehydrogenase. The present study was designed to provide a measure of corticosteroid secretion throughout the seasons using the in-vitro approach. Concomitant histological changes are also recorded and together provide evidence that the adrenal tissue of Rana rugulosa shows maximum activity in the spring spawning season and reaches a minimum in winter.
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SUMMARY
The monoamine oxidase inhibitor mebanazine (Actomol) was found to reduce the growth of cartilage, and the normal increase in body weight and pituitary weight in growing male rats. The inhibitory effect of mebanazine on cartilage growth is only partially overcome by concomitant injection of growth hormone. The inhibitory effect on growth is much greater when mebanazine is injected together with hydrocortisone; it exceeds by far the sum of the effects of mebanazine or hydrocortisone alone (augmentative synergism).
Mebanazine also inhibits cartilage growth in normal rats receiving metyrapone (Metopirone—which inhibits corticosteroid production) and in adrenalectomized animals receiving hydrocortisone. Mebanazine stimulates involution of the thymus and depletion of ascorbic acid from the adrenal glands of rats. This shows that mebanazine releases adrenocorticotrophic hormone in normal rats and in rats receiving high doses of hydrocortisone.
Our results thus suggest that the inhibitory effect of mebanazine on growth is twofold: it potentiates a corticosteroid which itself is a growth inhibitor and in addition blocks the release of growth hormone from the pituitary by a specific mechanism inherent in the action of mebanazine as an enzyme blocker.
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Search for other papers by RUTH A. LEONARD in
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SUMMARY
After the injection of cortisol into the toad Xenopus laevis, the concentration of steroid in the main circulatory system was much higher than that in the limb muscles. The concentration of corticosteroids in the blood fell at a faster rate than that in muscle. The particulate fraction of toad muscle homogenate bound added cortisol and some of it was not removed by repeated washing of the tissue with fresh medium. Bound steroid was not confined to any one subcellular fraction. The small particle fraction ('microsomes') contained the greatest proportion of steroid and the highest steroid concentration. The loss of corticosteroids from intact and washed particle preparations of toad gastrocnemius was not influenced by temperature over the range of 17–37°.
Copper, zinc and manganese (between 26 and 31 mm) inhibited the release of cortisol bound to muscle particles; p-chloromercuribenzoate (2 mm) and anoxia had no effect. A variation in pH from 2 to 10 made little difference to the rate of steroid release by muscle particles suspended in 0·15 m-KC1. The results suggest that the release of strongly bound steroids from muscle does not involve an enzymic mechanism.
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We have studied 16 patients with anorexia nervosa (11 with a stabilised weight loss and 5 in the weight-losing phase), 11 healthy controls, and 10 patients with Cushing's syndrome, by measuring plasma cortisol (by enzyme-immunoassay), ACTH (by RIA), corticosteroid (Type I-mineralocorticoid and Type II-glucocorticoid) receptors in mononuclear leukocytes (by radio-receptor assay), and lymphocyte subpopulations (by cytofluorimetry). In anorexic patients with a stabilised weight loss and in Cushing's syndrome the mean value of both Type I and Type II corticosteroid receptors in mononuclear leukocytes was significantly lower than in controls. The correlation between Type II receptors and plasma cortisol was inverse in stabilised anorexia nervosa and in Cushing's syndrome, and direct in healthy controls. Anorexic patients in the weight-losing phase showed a significant increase in plasma cortisol levels and a normal number of Type II receptors. From these results we hypothesise that in anorexia nervosa there is a progression from an increase in plasma cortisol in the weight-losing phase, to a concomitant decrease in Type II receptors when the disease is stabilised.
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Stilboestrol treatment increases the urinary excretion of corticosteroids in male guinea-pigs (Zondek & Burstein, 1952). This effect is presumably caused by stimulation of the output of adrenocorticotrophin (ACTH) from the hypophysis, but this has not been proved. The following experiments in hypophysectomized animals show that the effect is not produced in the absence of the hypophysis.
Four-month-old guinea-pigs of a randomly bred strain, anaesthetized intraperitoneally with 25 mg. tribromoethanol/kg. (Avertin, Winthrop Laboratories, New York) were hypophysectomized by the parapharyngeal approach (McPhail, 1934). The animals were allowed to recover in a warm (21–24°) draught-free room. Each animal was fed by pipette with warm milk 3 times a day until able to feed independently on cabbage and diet SG 1 (Dixon's, Ware). Cortisone was given daily (20 mg./kg., s.c.) for 1 week after the operation and the drinking water was replaced by a NaCl solution.
Guinea-pigs successfully hypophysectomized showed a smaller
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SUMMARY
The removal of a large clear cell adenoma (67 g.) from a patient in the Cardiff Royal Infirmary presented an opportunity to investigate the relative importance of alternative metabolic pathways to cortisol in adrenal tissue consisting primarily of a single cell type. Experiments were performed in which chopped tumour tissue was incubated simultaneously with [4-14C]pregnenolone and [7α-3H]progesterone for periods of time ranging from 5 to 120 min.
The conversion of these precursors to a variety of corticosteroids and intermediates was determined by radioisotope dilution techniques. From the results obtained, it was concluded that progesterone played only a minor role in the transformation of pregnenolone to cortisol in this tissue. It appeared that a large proportion of any progesterone formed from pregnenolone is rapidly metabolized to the 17-deoxycorticosteroids.
Search for other papers by G. P. VINSON in
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SUMMARY
Minced rat adrenal glands were incubated in vitro with [4-14C]progesterone and [16-3H]pregnenolone separately and together for 4 and 6 hr. periods. The yields of corticosterone, 11-deoxycorticosterone, and 18-hydroxy-11-deoxycorticosterone from both precursors, and of progesterone from [16-3H]pregnenolone, were estimated. In three incubations the change of these yields with time was also investigated. The results obtained suggest that in contrast to the human adrenal, and possibly those of other species, there is no distinction between the roles of progesterone and pregnenolone as precursors of corticosteroids in the rat adrenal gland. They suggest also that in the normal rat adrenal gland pregnenolone is transformed as follows:
Search for other papers by L. P. HEDNER in
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The reduction in plasma corticosteroid levels in man after administration of prednisolone, 16-methyleneprednisolone, triamcinolone and dexamethasone at four dose levels has been investigated. Homogeneous response variances and rectilinear log dose-response relationships were found for all of the preparations, thus providing a valid basis for a bioassay of the hypothalamus-pituitary depressing effect of these glucocorticosteroids. With respect to this effect, the relative potencies for the preparations in the order mentioned above were 1:0·64:1·63:17·5, and the index of precision for the log dose-response lines ranged from 0·19 to 0·39.
The requirements of the method are discussed and a comparison made with corresponding results obtained with other methods.
