THE EFFECT OF CORTICOTROPIN ON THE FORMATION OF CORTICOSTEROIDS IN VITRO

1961 ◽  
Vol 39 (1) ◽  
pp. 23-29 ◽  
Author(s):  
R. F. M. Barker ◽  
D. de Wied

The effect of endogenous corticotropin on the formation of corticoids in vitro was evaluated under different experimental conditions.Corticotropin, added in vitro to the adrenals of rats exposed to a strange environment, only moderately increased corticoid production, whereas the same amounts of corticotropin markedly stimulated the steroid formation of adrenals of "non-stressed" and hypophysectomized rats. Thus, the presence of endogenous corticotropin apparently interfered with the activity of added hormone.The adrenal response to corticotropin after preincubation was more pronounced than that of non-preincubated glands. It appeared that the preincubation medium contained corticotropin-inactivating material which could be destroyed by heating. This suggests that the preincubation medium contains an enzyme that inactivates corticotropin. Presumably, this enzyme leaks into the medium from the cut surface of the adrenal gland.

1961 ◽  
Vol 37 (2) ◽  
pp. 279-287 ◽  
Author(s):  
D. de Wied

ABSTRACT Intact, sham-operated, hypophysectomized rats and rats bearing extensive lesions in the median eminence were stressed by ether anaesthesia. The pituitary-adrenal response to the stress was determined on the in vitro steroidogenesis by adrenal gland slices of the left gland and on adrenal weight changes in the left and right gland. The absence of compensatory adrenal hypertrophy which normally occurs following the removal of the left gland, was used as an index of the inhibition of the secretion of ACTH (corticotrophin) from the adenohypophysis in the lesioned rats. Following ether stress, corticoid production in vitro of the left adrenal gland rose considerably in intact rats. Adrenal response to stress of sham-operated animals was almost similar to that of intact rats at 4, 66 and 162 hours but significantly depressed at 18 hours following operation. Hypophysectomized and lesioned rats, however, failed to exhibit an increased steroidogenesis in vitro following ether stress at the four time intervals studied. Pitressin markedly stimulated corticoidogenesis of adrenals of lesioned rats at 18. 66 and 162 hours following the production of lesions. The weight of the left adrenal gland of lesioned and hypophysectomized rats decreased gradually during the period studied; that of the latter group decreased at a faster rate. Adrenal hypertrophy, usually observed some time after placement of a lesion, did not occur in the lesioned rats of the present experiments. Weight increase of the right adrenal removed one week following extirpation of the left gland, was similar in intact and sham-operated rats, whereas this compensatory adrenal hypertrophy was absent in hypophys-ectomized as well as in lesioned animals.


1960 ◽  
Vol 38 (1) ◽  
pp. 1069-1075
Author(s):  
O. J. Lucis ◽  
E. H. Venning

Porcine, monkey, and human growth hormone have no effect on the in vitro secretion of aldosterone by the rat adrenal gland. When monkey growth hormone is injected into hypophysectomized rats, the adrenals of these animals secrete, under in vitro conditions, increased amounts of aldosterone with no change in the secretion rate of corticosterone. The plasma of these rats contains a substance which appears to stimulate the secretion of aldosterone in the adrenals of normal rats.


1965 ◽  
Vol 50 (1) ◽  
pp. 55-64 ◽  
Author(s):  
M. Staehelin ◽  
P. Barthe ◽  
P. A. Desaulles

ABSTRACT The adrenal gland response to natural or synthetic adrenocorticotrophic hormone was studied at various periods after hypophysectomy. Adrenal ascorbic acid depletion was observed following the administration of ACTH at all intervals up to 10 days. In contrast, the capacity to respond to ACTH by an increase in corticosterone secretion was rapidly lost. Experiments with rat adrenal slices in vitro showed that the capacity to form corticosteroids following the addition of ACTH or 3′,5′-cyclic-AMP is rapidly lost after hypophysectomy, but that the adrenal slices are still capable of producing corticosterone if NADP and glucose-6-phosphate are added to the medium. It is concluded that the adrenal gland is still capable of responding to the action of ACTH for a considerable time after hypophysectomy, but that due to a metabolic block prior to the formation of NADPH, the adrenal is no longer capable of reacting by a further increase in corticosterone production. In addition, it was found that the effects of ACTH on blood flow and ascorbic acid output were parallel. Both effects were dose-dependent, but independent of any concomitant corticosterone secretion, and persisted during the whole period studied after hypophysectomy.


1955 ◽  
Vol 33 (1) ◽  
pp. 677-680
Author(s):  
L.-P. Dugal ◽  
A. Desmarais ◽  
P. M. Gagnon

Modification of the response of the adrenal gland to ACTH was observed in hypophysectomized rats exposed to cold with or without ascorbic acid treatment. Changes in weight and metabolic activity of the gland were used to measure the adrenal response. All comparisons were made between the left and the right adrenal of each animal before and after treatment. The results obtained show that cold stress increases the response of the adrenal to a standard dose of two units of ACTH; they also indicate that ascorbic acid administration increases so much the responsiveness of the adrenal gland to ACTH at room temperature that such a response is not enhanced by exposure to cold.


1955 ◽  
Vol 33 (4) ◽  
pp. 677-680
Author(s):  
L.-P. Dugal ◽  
A. Desmarais ◽  
P. M. Gagnon

Modification of the response of the adrenal gland to ACTH was observed in hypophysectomized rats exposed to cold with or without ascorbic acid treatment. Changes in weight and metabolic activity of the gland were used to measure the adrenal response. All comparisons were made between the left and the right adrenal of each animal before and after treatment. The results obtained show that cold stress increases the response of the adrenal to a standard dose of two units of ACTH; they also indicate that ascorbic acid administration increases so much the responsiveness of the adrenal gland to ACTH at room temperature that such a response is not enhanced by exposure to cold.


1960 ◽  
Vol 38 (10) ◽  
pp. 1069-1075 ◽  
Author(s):  
O. J. Lucis ◽  
E. H. Venning

Porcine, monkey, and human growth hormone have no effect on the in vitro secretion of aldosterone by the rat adrenal gland. When monkey growth hormone is injected into hypophysectomized rats, the adrenals of these animals secrete, under in vitro conditions, increased amounts of aldosterone with no change in the secretion rate of corticosterone. The plasma of these rats contains a substance which appears to stimulate the secretion of aldosterone in the adrenals of normal rats.


1992 ◽  
Vol 126 (4) ◽  
pp. 363-368 ◽  
Author(s):  
Sandra H West ◽  
Jack R Bassett

From in vitro studies a circadian variation in adrenal gland response to ACTH was observed. Regulation of this circadian rhythm in adrenal responsiveness was localized to the cellular level; involving variation in either receptor density or affinity. In the present study the circadian variation in adrenal gland responsiveness was studied using an in vitro approach. Levels of corticosterone secretion during the active and inactive phases were determined using incubated rat adrenal slices in the presence and absence of submaximal stimulation by the synthetic ACTH peptide, ACTH(1–24). Initially, a circadian difference in adrenal responsiveness appeared to exist in all groups except the betamethasone pretreated. However, data expressed in terms of corticosterone secretion/mg adrenal weight proved to be misleading due to the presence of an apparent circadian pattern in adrenal gland weight; the adrenal glands from animals in the dark being significantly less in weight than those from animals in the light phase. When the data were expressed in terms of actual gland output, no circadian variation in adrenal response to exogenous ACTH(1–24) stimulation was apparent. In conclusion, the present study does not support the concept of a circadian variation in the adrenal response to ACTH(1–24) stimulation resulting from a variation in the responsiveness of the adrenal cells themselves. However, the present study does not preclude the possibility of a circadian variation due to modulation of adrenal responsiveness by humoral factor(s) other than ACTH.


1967 ◽  
Vol 54 (4) ◽  
pp. 645-662 ◽  
Author(s):  
Å. Hjalmarson ◽  
K. Ahrén

ABSTRACT The effect of growth hormone (GH) in vitro on the rate of intracellular accumulation of the non-utilizable amino acid α-aminoisobutyric acid (AIB) was studied in the intact rat diaphragm preparation. Bovine or ovine GH (25 μg/ml incubation medium) markedly stimulated the accumulation of AIB-14C by diaphragms from hypophysectomized rats, while there was no or only a very slight effect on diaphragms from normal rats. In diaphragms from rats with the pituitary gland autotransplanted to the kidney capsule GH in vitro stimulated the accumulation of AIB-14C significantly more than in diaphragms from normal rats but significantly less than in diaphragms from hypophysectomized rats. Injections of GH intramuscularly for 4 days to hypophysectomized rats made the diaphragms from these rats less sensitive or completely insensitive to GH in vitro. These results indicate strongly that the relative insensitivity to GH in vitro of diaphragms from normal rats is due to the fact that the muscle tissues from these rats has been exposed to the endogenously secreted GH. The results show that GH can influence the accumulation of AIB-14C in the isolated rat diaphragm in two different ways giving an acute or »stimulatory« effect and a late or »inhibitory« effect, and that it seems to be a time-relationship between these two effects of the hormone.


1968 ◽  
Vol 57 (3_Suppl) ◽  
pp. S19-S35 ◽  
Author(s):  
Å. Hjalmarson

ABSTRACT In vitro addition of bovine growth hormone (GH) to intact hemidiaphragms from hypophysectomized rats has previously been found to produce both an early stimulatory effect lasting for 2—3 hours and a subsequent late inhibitory effect during which the muscle is insensitive to further addition of GH (Hjalmarson 1968). These effects on the accumulation rate of α-aminoisobutyric acid (AIB) and D-xylose have been further studied. In presence of actinomycin D (20 μg/ml) or puromycin (100 μg/ml) the duration of the stimulatory effect of GH (25 μg/ml) was prolonged to last for at least 4—5 hours and the late inhibitory effect was prevented. Similar results were obtained when glucose-free incubation medium was used. Preincubation of the diaphragm at different glucose concentrations (0—5 mg/ml) for 3 hours did not change the GH sensitivity. Addition of insulin at start of incubation could not prevent GH from inducing its late inhibitory effect, while dexamethasone seemed to potentiate this effect of GH. Furthermore, adrenaline was found to decrease the uptake of AIB-14C and D-xylose-14C in the diaphragm, but not to change the sensitivity of the muscle to GH. Preincubation of the diaphragm for 3 hours with puromycin in a concentration of 200 μg/ml markedly decreased the subsequent basal uptake of both AIB-14C and D-xylose-14C, in the presence of puromycin, and abolished the stimulatory effect of GH on the accumulation of AIB-14C. However, the effect of GH on the accumulation of D-xylose-14C was unchanged. The present observations are discussed and evaluated in relation to various mechanisms of GH action proposed to explain the dual nature of the hormone.


1968 ◽  
Vol 57 (1) ◽  
pp. 23-32 ◽  
Author(s):  
Hironori Nakajima ◽  
Mitsunori Murala ◽  
Masumitsu Nakata ◽  
Takeshi Naruse ◽  
Seiji Kubo

ABSTRACT The in vitro resin uptake of 3H-prednisolone was used for the determination of blood cortisol after addition of radioactive prednisolone followed by Amberlite CG 400 Type 1 to the test serum, and incubation of the mixture. The radioactivity of the supernatant was compared before and after the addition of the resin. The principle of this method is similar to that of the 131I-triiodothyronine resin uptake for the thyroid function test. The tests for the specificity, reproducibility and sensitivity gave satisfactory results. The mean basal value ± SD of the 3H-prednisolone resin uptake was 35.3 ± 9.2% in normal subjects, and 27.1 ± 4.8% in pregnant women. This method was valid in various adrenal function tests, i. e. the adrenal circadian rhythm, corticotrophin (ACTH) test, dexamethasone suppression test and the adrenal response to lysine-8-vasopressin. It proved to be a sensitive indicator of the adrenal function. These results suggest that this method should be useful for a routine adrenal function test.


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