Effect of corticotropin and hydrocortisone on the Ca2+-ATPase activity of skeletal muscle sarcoplasmic reticulum

The effect of corticotropin (ACTH1-39), synacthen (ACTH1-24) and hydrocortisone-hemisuccinate on the activity of Ca-ATPase of skeletal muscle sarcoplasmic reticulum (SR) and calcium (Ca) accumulation in SR vesicles has been studied. It has been shown that ACTH1-39 (I U per 100 g body weight) increased the activity of Ca-ATPase in skeletal muscle SR of rats, while hydrocortisone (5 mg per 100 g body weight) did not change the activity of Ca-ATPase in skeletal muscle SR. However, both hormones increase the total activity of ATPase. ACTH1-39 and ACTH1-24 (0.05-0.0005 U/ml) and hydrocortisone (2.8 X 10(-7)-2.8 X 10(-9) mol/l) increased in vitro Ca-ATPase isolated from rabbit skeletal muscle SR and accumulation of Ca is SR vesicles. At the same time, hydrocortisone reduced calcium/phosphorus ratio, while ACTH1-39 and ACTH1-24 increased it, i.e. hydrocortisone facilitated Ca accumulation in SR requiring more ATP energy, whereas ACTH facilitated Ca accumulation in SR requiring less ATP energy.     

Concentration of free fatty acids in muscle following administration of corticotropin and hydrocortisone]

Experiments were conducted on rats; the gas chromatographic method was applied to the study of the free fatty acids content in the gastrocnemius 30 minutes after the intraperitoneal injection of adrenocorticotropic hormone (ACTH)--1 Unit per 100 g and hydrocortisone acetate--1 mg per 100 gm of body weight. It was shown that in the resting muscles ACTH increased the content of stearic acid, whereas hydrocortisone--of both stearic oleic acids. The changes in the content of other free fatty acids were insignificant. During the short-term activity the content of stearic acid in the regimen of single rhythmic contractions in the gastrocnemius of intact rats increased. In experiments with ACTH and hydrocortisone this elevation was much less and not significant. ACTH and hydrocortisone stimulated the stearic acid consumption by the muscles during the activity.     

Feedback inhibition of adrenocorticotropin release by corticosterone infusions in the adrenalectomized rat.

Advantage was taken of a specific and sensitive bioassay for rat plasma adrenocorticotropin (ACTH) based on the dispersion of rat adrenal cells with trysin, to investigate the relationship between plasma corticosterone concentration and inhibition of ACTH release under steady-state conditions achieved by graded rates (0-5.12 mug/min per 100 g body weight) of intravenous infusion of the steroid for 45 min in 28-day adrenalectomized rats. In contrast to prior reports involving suppression of stress-induced ACTH release, the inhibitory effect of corticosterone was shown, under our experimental conditions, to be exerted also on the basal rate of ACTH secretion. Indeed, a slight though not significant decrease of plasma ACTH concentration was observed with the corticosterone infusion rate of 0.64 mg/min per 100 g body weight, and further progressive and highly significant drops in concentration were recorded for infusion rates of 2.56 and 5.12 mg/min per 100 g body weight. An increase of the metabolic clearance rate of corticosterone, observed as a function of the infusion rate, was ascribed to saturation by the steroid of the plasma transcortin binding sites.     

Changes in the activity of the brain renin-angiotensin system and in the functional state of the pituitary-adrenal system of rats under the influence of captopril]

While studying the effect of peroral captopril injections on the activity of renin-angiotensin system (RAS), the activity of angiotensin-converting enzyme (ACE) and angiotensin II content from anterior and mediobasal hypothalamus, medulla and adenohypophysis of intact rats has been established to decrease. Captopril administration decreases ACE activity which increases after hydrocortisone injection in rat medulla and striatum. Captopril results in no potentiation of hormonal effect in hypothalamus and in adenohypophysis where ACE activity decreases following hydrocortisone injection. A decrease in the RAS activity of brain structures and adenohypophysis induced by captopril administration to rats is accompanied by the inhibition of the activity in the pituitary-adrenal system. A decrease in ACTH level and in 11-hydroxycorticosteroids of the rat blood plasma has been determined after single captopril injection in the dosage of 10 and 50 mg/kg of body weight. Duration of the effect depends on the captopril dosage.     

Adrenomedullary and glycemic responses to ACTH, corticosterone, aldosterone, epinephrine and norepinephrine administrations in the soft-shelled turtle

The aim of the current investigation was to ascertain the role of ACTH and adrenal hormones on adrenomedullary and glycemic functions in soft-shelled turtles, Lissemys punctata punctata. All the experiments were carried out on sexually immature animals. Findings revealed that: (1) ACTH administration (0.5 IU/1.0 IU/2.0 IU per 100 g body wt. daily for 10 days) in all doses stimulated adrenomedullary function by increasing medullary cell nuclear diameter with elevations of norepinephrine, epinephrine and blood sugar levels. Only moderate and higher doses (50 microg/100 microg per 100 g body wt. daily for 10 days) of dexamethasone suppressed adrenomedullary activity and blood sugar level by reversing the changes to those of ACTH; the responses were dose-dependent. But these changes were no longer observed after ACTH treatment in dexamethasone (DMS) recipients (DMS: 100 microg/ 100 g body wt daily for the first 10 days and ACTH: 0.5 IU / 100 g body wt daily for the next 10 days); (2) Only moderate and higher doses (50 microg/100 microg per 100 g body wt daily for 10 days) of corticosterone increased adrenomedullary activity and blood sugar level and the responses were also dose-dependent. But aldosterone treatment in all doses (same as for corticosterone) had no significant effect on the adrenal medulla or blood sugar level; (3) Only moderate and higher doses of norepinephrine or epinephrine (same as for corticosterone) caused adrenomedullary atrophy with depletions of norepinephrine and epinephrine levels but elevated the glycemic level. The findings are briefly discussed.     

Effect of neuromediating and neuroblockading hormones on the RNA synthesis in the rat liver nucleus

It was shown that rRNA and HnRNA synthesis in rat liver nuclei does not change-within 30 min after intraperitoneal injection of acetylcholine (0.005 mg per 100 g of body weight) but decreases after injection of norepinephrine and epinephrine (0.05 mg per 100 g of body weight). The synthesis of rRNA (but not of HnRNA) increases after injection of hydrocortisone (2,5 mg per 100 g of body weight). The synthesis of HnRNA (but not of rRNA) increases after injection of ACTH1-24 (3 ME per 100 g of body weight) and oxytocin (1 ME per 100 g of body weight). The synthesis of rRNA decreases after injection of propranolol and atropine (0.5 mg per 100 g of body weight). At the same time, the synthesis of HnRNA does not change thereby. The inhibitory effect of propranolol and atropine was corrected by electrostimulation of hypothalamus. The content of cAMP and Ca2+ and the phosphorylation degree of nuclear proteins are increased after stimulation of hypothalamus. The phosphorylation of nuclear proteins is increased by 10(-8)-10(-6) M cAMP. The synthesis of RNA in liver nuclei is increased by 10(-6) M cAMP only after addition of cytosol. In this case the activity of RNA-polymerase II increases in a greater degree than that of RNA-polymerase I + III. It is assumed that the regulatory mechanisms of rRNA and HnRNA synthesis are different. The role of hypothalamus electrostimulation, neurotransmitters, hormones, and cAMP in the mechanisms of RNA synthesis in rat liver nuclei is discussed.     

Membrane potential of muscle fibers exposed to corticotropin and hydrocortisone]

The effect of a single intraperitoneal administration of corticotropin (1 unit) and hydrocortisone (5 mg) per 100 g of a body weight on the membrane potential (MP) as well as on the response rate of miniature end plate potentials (RRMEPP) of musculus soleus fibres of various polarization levels has been investigated in rats. It is shown that administration of corticotropin does not change the MP value, while that of hydrocortisone elicits its increase at the low initial polarization level of the muscle fibre membrane and its decrease at the high level. Hydrocortisone administration does not change the MP value at normal levels of fibre polarization. Corticotropin having been administered, RRMEPP of fibres both with high MP levels and with low ones has increased. Fibres with normal polarization also show a tendency to increase. Administration of hydrocortisone has induced a substantial increase of RRMEPP in fibres with high polarization levels within 45 min, while PRMEPP of fibres with normal polarization levels increased within first 5 min., and that of fibres with low levels of polarization remained unchanged.     

ACTH-, glucose- and lactate-content of swine plasma during insulin-induced hypoglycemia]

The present investigation was undertaken to determine the content of ACTH, glucose and lactate in plasma of 4 pigs (body weight 82--118 kg) during a circadian period and during an insulin hypoglycemia test using 1 IU/kg in 3 pigs (body weight 96--118 kg) and 4 pigs (body weight 20--30 kg). The plasma ACTH level at rest was 57 +/- 27 pg/ml (Mean +/- SE) for all samples in all animals during a circadian period. Significant diurnal changes were not observed. During insulin-induced hypoglycaemia plasma ACTH rose from a mean (+/- SE) basal level of 35 +/- 15 to a maximum of 673 +/- 100 pg/ml at 60 min in heavier pigs and in lighter pigs to 395 +/- 153 at 30 min and 403 +/- 145 pg/ml at 120 min. Initial ACTH responses were evident 30 min (heavier pigs) and between 0 and 15 min (lighter pigs) after insulin administration. Plasma glucose decreased from a mean (+/- SE) basal level of 80 +/- 10 to a minimum of 6 +/- 1 mg/100 ml at 60 min (heavier pigs) and from 88 +/- 3 to 16 +/- 4 mg/100 ml at 60 min (lighter pigs). After its minimum level the glucose concentration showed a slower increment in the heavier pigs as compared to lighter animals. Plasma lactate rose from a mean (+/- SE) basal level of 19 +/- 10 to a maximum of 76 +/- 42 mg/100 ml at 120 min (heavier pigs) and from 12 +/- 3 to 37 +/- 16 mg/100 ml at 150 min (lighter group). In accordance with the changes in the blood plasma levels of ACTH, glucose and lactate, the clinical symptoms of hypoglycaemia in heavier pigs were more intensive.     

Cyclic adenosine-3',5'-monophosphate content in the limbic system structures of the rat brain on the administration of corticosteroids

The effect of hydrocortisone and DOCA on the cAMP content in the hypothalamus, hippocampus and striate body of the rat brain was investigated. Single (determined after 1 and 24 hours) and repeated (7 days) hydrocortison administration in a dose of 5 mg/100 g body weight was accompanied by an increase in the cAMP concentration in the brain structures under study. Single administration of DOCA in a dose of 0.5 mg/100 g body weight did not produce any changes in the cAMP level in the structures of the rat brain limbic system; however, the dose of 2.5 mg raised the cAMP level. Prolonged administration of the hormone in the above doses dod not change the cAMP level in the brain structures. Only the hippocampus showed a 210% increase in the cAMP level during DOCA administration in a dose of 0.5 mg.     

Aspartate and alanine aminotransferase activity in the tissues of adrenalectomized rabbits following administration of hydrocortisone and corticotropin

Aspartate and alanine aminotransferase (AsT, AlT) activities were studied in tissues of adrenalectomized rabbits which were treated with a single and multiple administrations of hydrocortisone (5 mg/kg) or a single administration of corticotropine (ACTH, 10 units/kg). It is shown that adrenalectomy decreases the AsT activity in homogenate of femoral muscle tissue and decreases the AlT activity in homogenate and supernatant of the liver, spleen and muscle tissue and in blood plasma. A single administration of hydrocortisone increases the AsT activity in supernatant of femoral muscle tissue and in blood plasma and increases AIT activity in the brain, liver, muscle and blood plasma. Parallel with that AsT and AlT activities are decreased in the spleen tissue. Multiple administration of hydrocortisone induces analogous changes in the AsT activity in the muscle and in the AlT activity in the liver, muscle and blood plasma. A single administration of ACTH induces an increase of the AsT activity in the muscle supernatant and in blood plasma. It also causes a rise of the AlT activity in the liver, muscle supernatant and blood plasma. The AlT activity is decreased in the brain supernatant. A question about stability of free amino acids metabolism (especially of alanine and aspartic acid) in the rabbit brain with changes in corticosteroid levels of organism is under discussion.     

Activity of some lysosomal enzymes in plasma and leucocytes of rabbits exposed to effect of retinol and hydrocortisone.

Observing activity of some lysosomal enzymes in blood serum and leucocytes of rabbits subjected to injection of 200,000 units of retinol and 25 mg of hydrocortisone/kg of body weight it was found that: 1. In the effect of retinol administration there was an increase in the activity AP, BGAL, BGLU, AspAT and lipase in blood serum after 72 hours and NAGL after 168 hours while in leucocytes BGAL and NAGL after 72 hours and AGAL after 168 hours. 2. As a result of hydrocortisone injection the activity of all the enzymes examined (except Ala-Na) in blood serum increased markedly already after 24-48 hours. 3. In leucocytes hydrocortisone caused a significant increase in the activity of AP, BGRD, NAGL, BGAL, AGAL and cathepsin D. 4. The glucose level in blood plasma decreased after 48 hours and 120 hours after hydrocortisone injection and 168 hours after retinol injection.     

Adrenocortical responses to adrenocorticotrophin in the rat

The time course of plasma adrenocorticotrophin (ACTH), adrenal cyclic AMP, adrenal corticosterone, and plasma corticosterone was measured in male Sprague-Dawley rats whose endogenous release of ACTH had been blocked (1) following rapid injections of 100 and 300 ng ACTH/100 g body weight, i.v., (2) during prolonged infusions at rates of 1, 2, and 4 ng ACTH/min per 100 g body weight, and (3) after termination of 30-min infusions at rates extending from 0.06 to 8 ng ACTH/min per 100 g body weight. Following injections, the time course of the variables is similar to the one simulated from our models of adrenal cortical secretion, including the simulation of an intermediate variable of our models of the adrenal cortex cell which was presumed to correspond to cyclic AMP. However, during prolonged infusions there is an unexpected overshoot of adrenal cyclic AMP content whereas adrenal and plasma corticosterone concentrations rise to a steady-state value without overshoot. The total amount of cyclic AMP gradually increases following the three increasing infusion rates of ACTH whereas similar levels of plasma corticosterone concentrations are reached at steady state; therefore the saturation of the adrenal cortical secretion is due to a step ulterior to cyclic AMP formation in the steroidogenesis. After 30-min infusions, plasma corticosterone concentration reaches its maximal value following a rate of ACTH input which evokes only a 4-fold increase in adrenal cyclic AMP content; however, there is a 250-fold increase of adrenal cyclic AMP with respect to control value following the higher rates of infusion of ACTH.     

Effect of hydrocortisone on ACTH, growth hormone, insulin and glucose in the blood of bilaterally adrenalectomized patients

This study is aimed at elucidating the mechanism of paradoxical rise in plasma ACTH levels in response to glucocorticoids, observed by several authors in bilaterally adrenalectomized patients with Cushing's disease. Six control subjects and fourteen patients bilaterally adrenalectomized for Cushing's disease were given a dose of 200 mg hydrocortisone sodium succinate by 3-5 mm i.v. injection. Plasma ACTH (in 6 patients), serum cortisol, growth hormone (GH) and insulin and blood glucose levels were estimated at 0, 30, 60, 90, and 120 minutes. The administration of hydrocortisone significantly suppressed plasma ACTH levels only at 60 min. In one case a slight rise in ACTH level during the test was observed. A significant fall in blood glucose levels was found only in the adrenalectomized patients. No significant changes in serum insulin and GH levels were noted. The possible mechanisms are discussed, especially the potential role of transient glucose deficiency in the pathophysiology of plasma ACTH increase in response to hydrocortisone in the bilaterally adrenalectomized patients.     

Effects of (D-ala2, met5)-enkephalinamide and naloxone on ACTH and corticosterone secretion

An intravenous administration of (D-ala2, met5)-enkephalinamide (DALA) caused a significant elevation of plasma ACTH and corticosterone at 10 to 20 min after injection in unanesthetized freely moving rats. An intraperitoneal administration of cyproheptadine tended to reduce plasma ACTH and corticosterone levels at 60 min after injection, but it did not attenuate the DALA-induced ACTH and corticosterone elevation. A large dose of naloxone (1-10 mg/kg body weight) caused a significant elevation in plasma corticosterone, but naloxone at 10 mg/kg body weight reduced the basal ACTH level and DALA-induced ACTH elevation. When both DALA and naloxone were injected, the steroidogenic effect was attenuated. Neither DALA nor naloxone affected the basal ACTH release and CRF-induced ACTH stimulation in rat anterior pituitary cell cultures. These results suggest that DALA acts at the extra-hypophyseal level to stimulate ACTH and corticosterone and that the naloxone stimulatory effect on steroidogenesis acts on the adrenal gland or is mediated by stimulating corticosterone stimulating factors other than ACTH.     

Effect of cold exposure on the concentration of triglyceride in the liver of the rat

The aim of the present study was to examine an effect of cold exposure on the concentration of triglycerides (TG) in the rat's liver. The rats were divided into the following groups: control, fed with oil, treated with hydrocortisone, fed with oil and treated with hydrocortisone, treated with noradrenaline. The rats exposed to cold were kept in wire cages (one rat in one cage) in the cold room at temperature +2 degrees C. They had free access to food (pellet diet for rodents) and water. In the control group the exposure to cold increased mildly (though significantly) the TG concentration after 1 and 3 h and had no effect after 2 and 24 h. It did not affect the concentration of plasma free fatty acids (FFA). At room temperature feeding with oil (2 ml/100 g of body weight) alone, and combined with hydrocortisone treatment (5 mg/100 g of body weight) as well as treatment with noradrenaline (0.1 mg/100 g of body weight) had no effect on the liver TG concentration, although the concentration of plasma FFA was increased. Exposure to cold for 3 h increased markedly the liver TG concentration in each of those groups. It is concluded that exposure to cold elicits a mechanism, which in the presence of elevated plasma FFA concentration induces accumulation of TG in the liver.     

Protective effect of propolis against oxidative stress and immunosuppression induced by oxytetracycline in rainbow trout (Oncorhynchus mykiss, W.)

The aim of this study was to investigate the effects of propolis on oxytetracycline (OTC)-induced oxidative stress and immunosuppression in fish. OTC (100 mg per kg?1 body weight) was orally administered to fish for 14 days. A significant elevation in the level of malondialdehyde, as an index of lipid peroxidation, and reductions in antioxidant enzyme activities (superoxide dismutase, catalase, and glutathione peroxidase) and low molecular weight antioxidant (reduced glutathione) levels were observed in the blood, liver, kidney, spleen, and heart tissues of OTC-treated fish. OTC also had a suppressive effect on specific and non-specific immune system parameters, such as leucocyte counts, oxidative radical production (nitrobluetetrazolium activity), total plasma protein and immunoglobulin levels, and phagocytic activity. Pre-treatment, post-treatment, and simultaneous treatment with propolis (50 mg per kg?1 body weight, orally) attenuated the OTC-induced oxidative stress by significantly decreasing the levels of malondialdehyde in tissues. In addition, propolis significantly increased the level of reduced glutathione and the catalase, glutathione peroxidase, and superoxide dismutase activities. Upon the administration of propolis, the suppressed immune system parameters were significantly increased in fish treated with OTC. The present results suggest that pre-treatment, post-treatment, and simultaneous administration of propolis might alleviate OTC-induced oxidative stress and immunosuppression.     

The effect of hydrocortisone on neutrophil functional activity

The male (CBA X C57BL) FI mice received 125 mg of hydrocortisone per kg body weight intraperitoneally. The functional activity of neutrophils has been evaluated by means of nitroblue terazolium test (NBT-test) values taken before or after heat-killed S. marcescens cell stimulation in vitro by 2, 12, 24 h 3, 7 or 14 days post hormonal treatment. Throughout the 1st day after hydrocortisone administration the NBT-test values taken prior to as well as post microbial neutrophil stimulation were steadily increased. This effect could be seen as early as 2 h post hormone administration and it was linked with growing leukopenia and total decrease of blood granulocyte content. By the 3rd day the same very values turned up to become normal. The NBT-test values after microbial stimulation of neutrophils were 1.7 or 2.4 lower after hydrocortisone had been added to blood in vitro in a dose 3.5 X 10(-6) M or 7 X 10(-5) M.     

Plasma immunoassayable ACTH levels during and after hydrocortisone infusion in patients with Cushing's disease.

The plasma ACTH responses to hydrocortisone infusion were compared in patients with Cushing's disease and primary adrenocortical insufficiency. In 4 patients with primary adrenocortical insufficiency, plasma ACTH levels were suppressed exponentially after administration of a relatively large dose of hydrocortisone (1.0 mg/kg/1.5 hr-3.0 mg/kg/2 hr). In patients with post-adrenalectomized Cushing's disease (4, bilateral; 1, unilateral), plasma ACTH suppression was delayed. Plasma ACTH levels, expressed as a percentage of the basal concentrations, were significantly less suppressed in patients with Cushing's disease than in patients with primary adrenocortical insufficiency 90 (p less than 0.05) and 120 (p less than 0.05) min after the beginning of infusion. When 0.5 mg/kg hydrocortisone was infused over a period of 1.5 hr, suppression was also delayed in Cushing's disease, and plasma ACTH levels were less suppressed in 4 patients with Cushing's disease than in 4 patients with primary adrenocortical insufficiency at 30 (p greater than 0.05), 45 (p greater than 0.05) 60 (p less than 0.05) min.     

Direct and indirect evidence for polypeptide absorption by the teleost gastrointestinal tract

The ability of the gastrointestinal tract of chinook salmon, Oncorhynchus tshawytscha , to absorb polypeptides in vivo was investigated by reference to the appearance of orally administered adrenocorticotropic hormone (ACTH) within the blood of fish previously treated with dexamethasone (3μg g^−l body weight) in order to suppress endogenous ACTH secretion. Further, since cortisol presence within plasma is dependent upon the availability of ACTH, dexamethasone blockade of endogenous ACTH secretion, in conjunction with subsequent measurements of plasma cortisol levels, provides a means by which biological patency of absorbed exogenous ACTH may be demonstrated. Levels of ACTH and cortisol in plasma of dexamethasone-treated salmon were therefore measured for a period of 360 min immediately following oral intubation of ACTH (15μg g⁻¹ body weight). Peak plasma presence of ACTH-like immunoreactivity (676.6 ± 33.6 pg ml⁻¹ plasma) and cortisol (227.1 ± 29.0 ng ml⁻¹ plasma) were recorded 120 min after ACTH administration. Results from the experimental groups were compared to those of 15 control treatments. Since administration of ACTH to chinook salmon elicited a consistent and significant elevation in not only plasma ACTH but also cortisol presence, it is contended that the salmonid gut expresses an ability to absorb polypeptides of dietary origin. The significance of these findings with respect to the oral administration of biologically active peptides and proteins to fish of importance to aquaculture is discussed.     

The effect of hydrocortisone on DNA synthesis by sebaceous gland epithelial cells]

The autoradiography method demonstrated a single injection of hydrocortisone (10 mg per 100 g of body weight) to result in suppression of the cell transition from the G1 phase of the mitotic cycle to the S phase and in prolongation of the S phase of the epithelium of the acinar portion (sebocytes) and stratified epithelium of the excretory ducts of the sebaceous gland of rats. Later, after a decrease of the proliferative processes by hydrocortisone there occurred their increase which was higher than control. Hydrocortisone induced a more pronounced effect on the proliferative activity of the stratified epithelium of the excretory ducts than on the sebocytes of the acini.