IU ACTH Research Articles

The effects of short-term undernutrition and adrenocortical stimulation on wool growth

SUMMARYSeven daily doses of 60 or 120 mg cortisol administered to mature sheep given a maintenance ration depressed wool fibre diameter by approximately 10%. Similar treatment with 120 mg cortisol for 14 days produced a more severe and prolonged effect, though fibre diameter was unaffected by a series of seven injections of 40 IU ACTH given every second day.Fourteen days at 10% of maintenance and 14 days' cortisol treatment were applied to mature sheep fed either continually at 150% maintenance, or at 75% followed by 150% maintenance. Cortisol treatment was associated with a significant reduction in fibre diameter only in the animals fed at 150% maintenance. Restriction to 10% maintenance for 14 days had no such effect. Approximately 20% of fibres were shed following cortisol treatment in both nutritional groups, but a marked ‘break’ in the fleece occurred only in the 75% maintenance group.A low plane of nutrition is confirmed as a major factor predisposing to ‘tenderness’ and ‘break’, and short-term adrenocortical stimulation is shown to be sufficient to produce the reduction in fibre diameter and increased fibre shedding associated with these faults. However, semi-starvation (represented by restriction to 10% of maintenance) appears to have played a relatively minor role in their development.

Adrenocorticotropin Alteration of Bovine Peripheral Plasma Concentrations of Cortisol, Corticosterone, and Progesterone ,

Seven Holstein cows, 60 to 90 days postpartum, received either 200 IU ACTH (n=4) or saline (n=3) intravenously with treatments reversed 2 days later. Blood samples (30ml) were collected from indwelling jugular catheters at −60, 0 pre-injection, and 5, 15, 30, 45, 60, 120, 180, and 240min postinjection. Solvent extraction, purification by Sephadex LH-20 column chomatography and competitive protein-binding analyses were used to isolate and quantify plasma cortisol, corticosterone, and progesterone. Mean cortisol (ng/ml) at the respective sampling times was 3.1 vs. 3.6 (saline vs. ACTH), 4.9 vs. 4.1, 5.9 vs. 33.7, 8.8 vs. 30.0, 4.8 vs. 45.8, 3.3 vs. 28.8, 3.2 vs. 31.3, 4.4 vs. 36.6, 2.6 vs. 26.8 and 5.2 vs. 34.7. Both the magnitude of the cortisol response and the interval to maximum response to ACTH varied among cows (P<.01). Adrenocorticotropin elicited a corticosterone increase (P<.01) concurrently with the cortisol increase, but it was of lower magnitude, reaching 7.6ng/ml at 30min. Mean progesterone at the respective times was 1.7 vs. 2.1, 2.4 vs. 2.0, 2.0 vs. 3.1, 2.0 vs. 4.5, 2.2 vs. 4.2, 2.5 vs. 4.2, 2.2 vs. 3.9, 2.3 vs. 2.4, 2.6 vs. 2.8 and 2.2 vs. 2.0ng/ml, and the increase due to ACTH administration was significant (P<.025) between 15 to 60min post-injection. Results suggest that the adrenal contributes a significant proportion of plasma progesterone.

Lack of hypertrophy of the adrenal in exencephalic fetal rats subjected to hypervitaminosis A and then to maternal adrenalectomy.

Mother rats were treated daily with 30,000 USP units of vitamin A on the 8th, 9th and 10th days of gestation. Subsequently, some of them were adrenalectomized on the 20th day of gestation or were subjected to laparotomy for the injection of 1 IU of ACTH to each exencephalic fetus on the 21st day of gestation. Autopsy was performed on the 22nd day of gestation. Maternal hypervitaminosis A induced exencephaly in some fetuses in which the growth of the adrenal was retarded despite the presence of the anterior pituitary. Maternal adrenalectomy did not cause a significant hypertrophy of the fetal adrenal in exencephalics but did in non-exencephalics in the same litter. The adrenals of exencephalics given ACTH were enlarged significantly. The observations suggest that the fetal brain-pituitary region plays an essential role in the mechanism of hypertrophy of the fetal adrenal following maternal adrenalectomy. (Endocrinology 88: 1526, 1971) T ADRENALS of anencephalic or hydrocephalic human fetuses are invariably small, regardless of the presence or absence of the anterior pituitary (1). Similar retardation of the adrenal growth has been observed in fetal rats under various experimental conditions such as complete removal of the hypothalamus by decerebration of a fetus (2), destruction of the fetal hypothalamic area with an electrocoagulator, compression of the fetal brain by intracranial paraffin injection, and induction of fetal exencephaly by hypervitaminosis A (3). These observations suggest that the brain, including the hypothalamus, is necessary for the growth of the adrenal during prenatal life. However, such observations still do not necessarily rule out the possibilities of partial autonomy of the fetal pituitary-adrenal axis or some influence of maternal CRF on the axis. The present studies were carried out to compare the extent of retardation of the adrenal growth in the absence of the pituitary with that which occurs when the brain is defective and to examine to what extent the adrenal of a fetus in which the brain was destroyed could enlarge following maternal adrenalectomy. The defect of the fetal brain was induced by maternal hypervitaminosis A. Materials and Methods Rats of the Wistar strain were used. They were given a commercial diet (Oriental pellets NMF) and water, both ad lib. Days of gestation were counted from the day following an overnight matReceived June 2, 1970. ing, which was counted as the 1st day of gestation. The experimental groups and designs were: Group 1. Mother rats were subjected to midventral laparotomy under ether anesthesia on the 20th day of gestation in order to decapitate surgically 3 or 4 fetuses in utero in each litter by the method of Domm and Leroy (4) for the purpose of hypophysectomy. Two days later, at autopsy, these decapitated fetuses were matched at random with intact litter-mate fetuses of the same sex. Group 2. Mother rats were adrenalectomized on the 20th day of gestation via the dorsolumbar approach. Subsequently, on the same day, they were subjected to laparotomy and 2 or 3 fetuses in each litter were decapitated. Two days later, autopsy was performed. Group 3. Mother rats were treated daily with 30,000 USP units of vitamin A palmitate (Sigma Chemical Co.) suspended in 0.6 ml of saline by a stomach tube on the 8th, 9th and 10th days of gestation. Autopsy was performed on the 22nd day of gestation. Litters in which all or none of the fetuses showed exencephaly were discarded. In each litter used, exencephalic fetuses were matched at random with non-exencephalic fetuses of the same sex. The remaining odd fetuses were discarded. Group 4. Mother rats were treated with vitamin A as in group 3. They were subjected to adrenalectomy on the 20th day of gestation. Exencephalic fetuses were paired with litter-mate non-exencephalic fetuses in the same way as in group 3. Group 5. Mother rats were treated with vitamin A as in group 3. They were subjected to laparotomy on the 21st day of gestation for the injection of

Effect of nicotinic acid on ACTH and noradrenaline stimulated lipolysis in the rabbit. I. In vivo studies.

AbstractACTH, 50, 10, 2 and 0.5 IU/kg b.w. and noradrenaline, 1.0 μg/kg/min were given i.v. to fed, unanesthetized rabbits either pretreated with nicotinic acid or not.Both ACTH and noradrenaline increased arterial concentration of free fatty acids (FFA). For noradrenaline this effect was present only in rabbits with lower body weight and furthermore the effect was less pronounced and of shorter duration than for ACTH.Nicotinic acid inhibited partly the increase of plasma FFA caused by 0.5 IU of ACTH but not that after the higher doses. Nicotinic acid had sometimes but not always an inhibitory effect on the increase caused by noradrenaline while nicotinic acid by itself did not change the basal levels of plasma FFA.

Extra-adrenal action of adrenocorticotropin on cortisol metabolism.

ABSTRACT To elucidate the extra-adrenal action of ACTH on cortisol metabolism, the influence of ACTH on the biological half-life, apparent distribution volume and urinary metabolites of cortisol were studied in 15 patients with adrenal insufficiency (7 patients with Addison's disease and 8 adrenalectomized-oophorectomized patients). Plasma cortisol disappearance was studied after a 30-min intravenous administration of 1 mg of cortisol/kg of body weight. After several days, the same test was repeated with the intravenous infusion of 50 IU of ACTH over 6 hr. During ACTH infusion, the plasma free 17-OHCS level was lower at the 1st and 2nd hr after the beginning of cortisol infusion, the extrapolated C0 value was significantly lower and the apparent distribution volume of infused cortisol was larger than that obtained at the comparable time without ACTH administration. On the other hand, the half-life of 17-OHCS from plasma was prolonged during ACTH infusion. These data suggest that ACTH accelerates the trans...

Cortisol and Corticosterone in Bovine Plasma and the Effect of Adrenocorticotropin1,2

Plasma levels of cortisol and corticosterone were determined in 18 lactating, nonpregnant dairy cows of three breeds and also at hourly intervals following a single injection of 200 IU ACTH to five cows and no treatment to one cow. The mean for all breeds was 7.3μg cortisol per 100ml plasma. The cortisol of Guernseys was 5.2±2.4 (mean±SD) μg per 100ml plasma, which was significantly lower (P<0.01) than in Holsteins (9.3±2.4); whereas, cortisol levels in Jerseys (7.4±1.5) were not significantly different from the two other breeds. The mean was 3.0 μg corticosterone per 100ml plasma, with no significant differences between breeds. Administration of ACTH more than doubled the plasma concentration of cortisol in one hour, resulting in highly significant (P<0.01) treatment effects between hours post-treatment, whereas only a 33% increase was found in the untreated cow. A significant (P<0.05) linear downward trend in corticosterone level and a significant (P<0.05) quadratic effect on the cortisol: corticosterone ratio were also found following ACTH treatment. This would appear to indicate that ACTH treatment preferentially stimulated the 17-hydroxylating system of the bovine adrenal.

Prevention of drop in adrenocortical activity in the 7-day-old rat by pretreatment with ACTH.

SummaryIt was demonstrated that the plasma corticosterone response to ACTH is extremely weak in the 7-day-old rat. The present results indicate that pretreatment with 2 IU of ACTH in a beeswax-oil suspension on day 5 of age resulted in a 7-day-old rat that is capable of responding to ACTH in a manner comparable to that seen in younger and older rats. It is concluded from these studies that the “biphasic pattern” seen in the neonatal rat (characterized by a depressed adrenal response at day 7) is due to a depressed ability of the adrenal cortex to respond to ACTH. The hypothesis is presented that the depressed ability of the adrenal cortex to respond is the result of a relative lack in circulating ACTH. It is suggested that decreased ACTH secretion is the result of a failure of CRF to get to the pituitary because the hypothalamic-pituitary system is not complete in the 7-day-old rat.

Interruption of pregnancy in the rat by administration of ACTH.

Intraperitoneal injections in the rat of 12 IU ACTH on Days 1, 2 and 3 after mating resulted in a marked inhibition of both implantation and fetal development to 57 and 29%, respectively, of control values, but did not alter the rate of tubal transport or development of the ova. Following similar treatment with 3, 6 or 12 IU ACTH on Days 5, 6 and 7, both implantation and fetal development were reduced (to 80, 74 and 57% and 75, 61 and 39%, respectively). About 52% of the blastocysts transferred from donors receiving 12 IU ACTH on Days 1, 2 and 3, and 56% of the blastocysts from untreated donors developed into normal fetuses when transferred to the left or right uterine horns of recipients. Daily injections of 12 IU ACTH on Days 5, 6 and 7 with implants of 10 mg cortisone pellet on Day 5 resulted in a significantly high fetal mortality in intact females but not in females adrenalectomized on Day 5. In pregnant rats adrenalectomized on Day 5, a 10 mg corsisone pellet maintained pregnancy, whereas smaller (5 mg) or larger doses (20 or 40 mg) we re less effective. It thus seems likely that the effect of ACTH on the embryos was chiefly an indirt ct effect mediated through the adrenal gland, a:id that the antifertility effect of ACTH was {attributable to excessive production of corticosseroids by the adrenal. (Endocrinology84: 1282, 1969)

SERUM ORNITHINE CARBAMOYL TRANSFERASE ACTIVITY (S‐OCT) AFTER IRRADIATION OF MALIGNANT TUMOURS AND AFTER ADMINISTRATION OF ACTH

Abstract. A group of 20 women who received radiation therapy for cancer of the uterine cervix displayed a significant rise of S‐OCT 4–6 days later. This rise can hardly be explained by an increased adrenocortical stimulation elicited by the trauma because a corresponding stimulation (90 IU ACTH) in ten healthy subjects resulted in a significant drop in S‐OCT. A study of the nitrogen balance in six other subjects showed that adrenocortical stimulation with 90 IU ACTH did not lead to any increase in the breakdown of protein. These observations seem to support the theory that the increases in S‐OCT that were observed a few days after conditions involving an elevated breakdown of protein may be due to a release of some of the additional amount of OCT that is supposedly formed in the human liver during the maximal breakdown of protein.

THE ORIGIN OF URINARY DEHYDROEPIANDROSTERONE IN BOARS.

ABSTRACT Dehydroepiandrosterone, generally regarded as a compound formed peripherally from 17-hydroxy-pregnenolone (3β,17-dihydroxy-pregn-5-en-20-one), a steroid present in the adrenal glands, is the most important neutral 17-ketosteroid occurring in the urine of the male domestic swine. However, the excretion of Zimmermann chromogens in boars was not found to increase significantly following the administration of ACTH (2 × 40 IU) and a long-acting ACTH (2 × 50 IU): after the injection of chorionic gonadotrophin (3 × 10 000 IU), the excretion increased in intact boars. In a castrated animal, administration of 3 × 150 IU ACTH and 2 × 120 IU ACTH did not cause an increase in the excretion of Zimmermann chromogens, nor was there any effect after the administration of 3 × 10 000 IU chorionic gonadotrophin. Moreover, the bilaterally castrated animal had a lower basal excretion of Zimmermann chromogens than an intact boar of the same age. The conclusion is reached, that in boars the contribution of the adrenal cortex to the dehydroepiandrosterone excretion is of minor importance. Instead of the adrenal cortex, the testes must be considered as the main source of the precursor of the dehydroepiandrosterone excreted in the urine.

Effect of chlorpromazine on pituitary-adrenal function in the dog.

ABSTRACT The response of the adrenal cortex to psychic and surgical stress and to exogenous ACTH has been investigated in dogs following the acute and chronic administration of chlorpromazine. Administration of 2.5 mg/kg intravenously followed by 2.5 mg/kg over a ½-hour period to stressed dogs did not decrease adrenal 17-hydroxycorticoid output significantly, while surgical hypophysectomy caused a marked drop in the same time interval. In dogs given 30 mg/kg/day, the rise in peripheral plasma 17-hydroxycorticoids following 2 hours of immobilization was normal after 3 days of treatment, and the response to surgical stress and to 1 IU of ACTH was normal in dogs treated for 5 days. After hypophysectomy, 17-hydroxycorticoid output in chlorpromazine-treated dogs in response to 2, 5, and 10 mU doses of ACTH was slightly greater than normal, probably due to the mild adrenal hypertrophy produced by the drug. Chlorpromazine does not interfere with the determination of 17-hydroxycorticoids by the Silber-Porter method.

The Effects of Corticosteroids on Kidney Functions (I) Studies on the Effects of Corticosteroids on Electrolytes Transport of Renal Tubuli by Stop Flow Method

Malvin and others developed a new method to visualize the localization of tubular reabsorption of various substances by relatively simple stop flow technique. In this paper the author presents studies on the effects of various corticosteroids on tubular transport of electrolytes and its localization by this technique. Materials and method Dogs weighing 15-10kg were divided in 6 groups. 1) Control group received intravenous drip of glucose saline for the osmotic diuresis as indicated in Malvin's technique. Drugs to be tested were dissolved in the glucose saline above cited and injected intravenously. Their doses were as following. 2) Desoxycorticosterone glucoside 1 mg/kg. 3) Hydrocortisone hemisuccinate 10mg/kg, 4) Dexamethasone phosphate 0.8mg/kg and 0.4mg/kg. 5) Single intravenous injection of 20 IU ACTH and successive injection of ACTH for 4 days (20 IU i. m., 10 IU i. m., 10 IU i. m., 20 IU i. v.) 6) Hydrochlorothiazide 10mg/kg. Na and K were determined by flame photometer, Cl by Schales & Schales, PAH by Tsuda's method, Cratinine by Jaffe's method. From each samle of all urine collections, U/P/(U/Pcr) was calculated, where U/P is the concentration ratio of urine and plasma with the tested substance and U/Pcr is that with creatinine. To illustrate the localization of the tubular reabsorption U/P/(U/Pcr) was plotted to percent volume within kidney from left (distal) to right (proximal). Results a) The patterns of control group were very similar as Pitts and others published previously. (Table I, Fig. 1) b) Hydrochlorothiazide inhibited markedly the reabsorption of Na and Cl in distal tubuli. Increased secretion of K was observed also in distal tubuli. (Table I, Fig. 2) c) D O C increased Na and Cl reabsorption in distal and proximal tubuli. Peak of K in distal tubuli was not significant. (Table I, Fig. 3)