17-OHCS Levels Research Articles

INSULIN, GLUCAGON AND 11-OHCS RESPONSES TO ARGININE IN CALVES EXPOSED TO COLD

Moderate cold exposure (2 °C) promoted the basal levels of plasma insulin, glucagon, 11-OHCS and glucose in calves. Each determined value showed a peak 5 min after arginine injection. The peak values were promoted by the cold exposure. Key words: Calf, arginine, insulin, glucagon, 11-OHCS, cold

Effect of intermittent (traffic) noise on man--temporary threshold shift, and change in urinary 17-OHCS and saliva cortisol levels.

Eight healthy male college students were selected and eight noise exposure conditions were planned. The noise exposure time of all the experiments was 14 h. Measurement of the TTS growth at 4 kHz was investigated during these 14 h. Saliva collected every 3 h was also examined for cortisol throughout the 24-h period. The exposure noises used in this experiment were pink noise and pure tone of 3 kHz. The time patterns of trapezoidal noise were as follows. The rise and decay times were 1 s respectively and the peak level was 1 s for the (A I type), being 500 ms and 1.5 s respectively for the (A II type). Three measurements were made: 1. TTS. Under intermittent noise exposure at 80 dB(A), exposure of 20% of the on fraction induced significant TTS growth, but exposure of 13% of the on fraction did not induce TTS growth. Under exposure at 75 dB(A), exposure of 66% of the on fraction did not induce TTS growth. Under pure tone exposure of 3 kHz at 75 dB(A), exposures of 20% and 30% of the on fraction did not induce TTS growth. There was a significant difference between the TTS induced by a steady state of of 73 dB (A) (Leq of Exp. 2) and that of Exp 2. 2. Urinary 17-OHCS Level. During the noise exposure period (14h), there was a statistically significant difference between the urinary 17-OHCS level of the control condition and that of Exp. 3. In addition, there was no statistically significant difference among the urinary 17-OHCS levels of post-noise exposure. 3. Saliva Cortisol. With intermittent "pink noise" of 75 or 80 dB(A) (Exp. 2, 3, and 4), however, temporary elevation of the saliva cortisol level occurred only at the initial stage of exposure, and lasted for only one hour. Moreover, with steady state noise exposure, evanescent elevation occurred at the lower level of 71 dB(A).

Isolated ACTH Deficiency

Isolated adrenocorticotropin (ACTH) deficiency is a rare cause of secondary adrenocortical insufficiency. This review summarizes the clinical and laboratory features of 39 previously reported cases plus 4 new patients. The clinical manifestations of isolated ACTH deficiency are variable, nonspecific and similar to those seen in adrenocortical insufficiency of any cause. The diagnosis of isolated ACTH deficiency due to intrinsic pituitary disease is made unequivocally when all the following criteria are met: 1) low basal urinary 17-hydroxycorticosteroid (17-OHCS) levels with or without low basal plasma cortisol, 2) low or normal basal plasma ACTH, 3) stimulation of cortisol, 17-OHCS or both during prolonged ACTH administration, 4) lack of 17-OHCS elevation in response to metyrapone and 5) normal secretory indices of other pituitary hormones. Isolated ACTH deficiency secondary to suprapituitary (e.g., hypothalamic) dysfunction is also based upon the above criteria, but, in addition, is associated with stimulation of cortisol and ACTH secretion following vasopressin administration.

α-MSH, MIF-I and melatonin: Effects on novelty-induced defecation, plasma 11-OHCS and central catecholamines in rats

The pituitary-hypothalamo-pineal complex involving MSH, MIF-I and melatonin has been strongly emphasized in the adaptive mechanism of the animal. A series of experiments was conducted to investigate the effects of α-MSH, MIF-I and melatonin on novelty-induced defecation, step-down activity, plasma 11-OHCS levels and whole brain DA and NE concentrations over days of novelty×drug treatment. α-MSH consistently enhanced and sustained novelty-induced defecation, increased plasma 11-OHCS levels in the resting intact rats and in the novelty exposed hypophysectomized (hypox) rats, and decreased brain DA and NE levels in intact, hypox and sham-hypox rats. MSH did not increase plasma 11-OHCS in intact and sham-hypox rats during exposure to novelty. MIF-I significantly habituated novelty-induced defecation and increased brain DA and NE levels over 5 days of drug×novelty treatment. Melatonin, on the other hand, inhibited novelty-induced defecation, decreased plasma 11-OHCS and increased brain DA level over 5 days of melatonin×novelty treatment. MSH, MIF-I or melatonin did not show any significant effect on the step-down activity of the rats. The results suggest the possibility that central CAs may be implicated in the behavioral changes observed after α-MSH, MIF-I and melatonin administration and in the interaction of the pituitary-hypothalamo-pineal complex involving MSH, MIF-I and melatonin.

Effects of α-MSH and melatonin on passive avoidance and on PA-induced defecation and plasma 11-OHCS in hypophysectomized rats

The present study shows that α-MSH facilitates the acquisition and delays the extinction of a Passive Avoidance Response (PAR) in the hypox animals. MSH exacerbates PA-induced defecation in both hypox and sham-hypox animals. Hypox and sham-hypox animals treated with MSH do not differ on PAR or on PA-induced defecation. Melatonin, on the other hand, has no significant effect on PAR in hypox rats, but retards acquisition and facilitates extinction of the PAR in sham-hypox rats. Melatonin also inhibits PA-induced defecation in sham-hypox rats. Sham-hypox and hypox rats treated with Melatonin do not differ on PAR learning, retention (Extinction) and PA-induced defecation. MSH and Melatonin also seem to have opposite effects on plasma 11-OHCS levels measured at the end of PAR extinction. MSH increases plasma 11-OHCS in hypox rats, whereas Melatonin decreases plasma 11-OHCS in sham-hypox rats. Melatonin does not lower further the very low level of plasma 11-OHCS in hypox rats.

α-MSH effects on novelty-induced defecation, plasma 11-OHCS and whole brain catecholamines in hypophysectomized rats

The effect of hypophysectomy on novelty-induced defacation was found to be inhibitory in nature, but this effect was reversed by treatment with α-MSH. MSH-treated hypox rats maintained, over days, novelty-induced defecation and showed a significant elevation in plasma 11-OHCS levels, compared with the levels of control-injected counterparts. MSH treatment also reduced over Days 1 to 5 the whole brain DA and whole brain NE levels in hypox animals. Control-treated hypox rats, however, showed an increase in brain NE concentration which was significantly reduced by MSH treatment. Sham-hypox animals also sustained novelty-induced defecation after MSH treatment but did not show a significant rise in plasma 11-OHCS level. Whole brain DA and whole brain NE levels in sham-hypox rats were also reduced significantly by MSH treatment. The behavioral maintenance of defecation in hypox and sham-hypox rats seem to be concomitant with significant reductions in whole brain catecholamines.

Life events, 17-OHCS measures, and psychological defensiveness in relation to aid-seeking.

Professional aid-seeking for medical or psychological reasons was measured in 80 firefighters for a retrospective period of six months and a prospective period of eight weeks. The magnitude of life stress events, 24-hour urine 17-OHCS levels, and MMPI K-Scale scores were compared between those subjects who had sought professional aid and those who had not. The measured values did not differ significantly between groups and were, in fact, well within normal limits for all subjects tested. Analysis suggests that implied relationships between stress and illness are questionable in low-stress, low-maladjustment populations. These data lend support to the concept of a threshold effect for influence of life change on subsequent illness manifestation.

Resistance to inhibiting effect of dexamethasone in patients with endogenous depression.

Suppression of 11-hydroxycorticosteroids (11-OHCS) release with dexamethasone (0.5 mg) has been investigated in 52 patients with endogenous depression and also in normals and in patients with other mental diseases. The suppression was considerably less in depressives (-19 +/- 5%) than in control groups (approx. -60%). The dexamethasone test indices were normalized during remission. The elucidate mechanisms of the dexamethasone inhibiting effect, the influence of tryptophan, DOPA and benzodiazepines on the 11-OHCS level and the degree of its suppression with dexamethasone have been studied. The data indicate a dual effect of serotonin on the regulation of the adrenal function: it stimulates CRF secretion and increases the inhibiting effect of corticosteroids on CRF release. It is suggested that during depression the negative feedback is disturbed in the system - brain monoamines-glucocorticoids. The possible role of this impairment in depression pathogenesis is considered.

The interaction of a fixed time food delivery schedule and body weight on self-administration of narcotic analgesics

Experiment 1 reported the effects of the interaction of a fixed 1 min delivery schedule and body weight, using schedule-induced self-injection paradigm, in the rate of acquisition of methadone and heroin. Eighty-one rats were assigned to 100% and 80% reduced body weight conditions with and without a schedule. The findings show that: (a) voluntary heroin and methadone intake was enhanced when a schedule was introduced to animals at 80% but not at 100% body weight; (b) high intake of heroin and methadone was accompanied by increased levels of plasma 11-OHCS. Experiment 2 showed that the high rate of self-injection was due to the interaction of pharmacological properties of opiates and environmental variables rather than to a general increase in activity arising from the deprivation state or the effects of the schedule. The results are discussed in terms of a stress factor arising from an interaction between environmental and pharmacological factors.

Alpha-MSH- and novelty-induced emotional responses in rats: associated changes in plasma corticosterone and brain catecholamines.

In a series of experiments it was demonstrated that defecation responses induced in rats by exposure to novel environments did not habituate if the animals were treated with alpha-melanocyte stimulating hormone (alpha-MSH). The MSH-treated rats sustained high defecation responses on 6 successive days of exposure, whereas control rats habituated. The role of plasma 11-hydroxycorticosterone (11-OHCS) levels and brain catecholamines (CAs) in this novelty-induced defecation following alpha-MSH administration was also investigated. Baseline studies showed that MSH treatment alone increased plasma 11-OHCS levels in the resting condition and lowered brain dopamine (DA) but not norepinephrine (NE) concentrations. It was found, however, that plasma 11-OHCS levels in MSH-treated rats were not significantly increased on successive days of combined MSH and novelty treatments but that whole brain DA and NE concentrations were both lowered. A strong negative correlation was observed between defecation responses and brain DA concentrations on successive days of the joint MSH and novelty treatment. In all the experiments alpha-MSH treatment had no effect on step-down activity.

A Prospective Study of Corticosteroid and Catecholamine Levels in Relation to Viral Respiratory Illness

Urinary 17-OHCS, epinephrine and norepinephrine levels were studied for one week before and one week after the onset of acute, severe Adenovirus 4 respiratory illness in 12 Army recruits during Basic Combat Training. During the pre-illness period, a tendency was frequently noted for all three hormone levels to show "spiking" elevations two to four days before illness onset. There was also a tendency for 17-OHCS levels to rise on the day before fever onset. The possible relationship of these pre-illness hormonal changes to stressful experiences and, in turn, to altered host resistance to infectious illness is discussed. Following onset of respiratory illness, 17-OHCS, epinephrine and norepinephrine levels all showed about 60 percent increases over the early pre-illness period baseline value. Elevations of these hormones persisted for about four to five days, roughly in correlation with fever duration, with only slight differences in configuration and timing of curves from one hormone to the next. The problem of evaluating which of several independent variables operating concurrently during infectious illness may be responsible for stimulating the final common neuroendocrine pathways is discussed.

Effects of MIF-I and melatonin on novelty-induced defecation and associated plasma 11-OHCS and brain catecholamines

In two experiments the effects were investigated of MSH-inhibiting factor-I (MIF-I) and of Melatonin on step-down latencies, defection, plasma 11-OHCS levels, whole brain DA and whole brain NE concentrations on Days 1, 3 and 5 of novelty exposure. Treatment with MIF-I led to a significant habituation of novelty-induced defecation over 5 days, whereas plasma 11-OHCS level was reduced only on Day 1. The concentrations of whole brain DA and whole brain NE also showed a significant increase over days of MIF-I and novelty treatment. Melatonin treatment, on the other hand, significantly inhibited novelty-induced defecation and reduced plasma 11-OHCS level on Day 5 of novelty exposure. Melatonin treatment led to a significant increase of whole brain DA in animals exposed to novelty for 5 days. Neither MIF-I nor Melatonin was found to significantly affect the step-down activity of treated animals. The overall results suggested a possible relationship between novelty-induced defecation and brain DA levels of MIF-I and Melatonin treated animals.

The hippocampus and stress induced 17-OHCS elevations

The physiologic contribution of the limbic brain to emotionally induced stress is still poorly understood. The present study is designed to more specifically evaluate the role of the hippocampus in stress induced plasma 17-OHCS elevations. The conditional reflex to a sequential presentation of tone and shock was used as the stress agent in adult mongrel dogs. Plasma 17-OHCS levels were determined by the Porter-Silber method. Control and stress levels of 17-OHCS were determined before and after unilateral (left) hippocampectomy, and subsequent contralateral (right) hippocampectomy. A unilateral posterior hippocampal lesion partially attenuated (20%) the normal 17-OHCS stress response. In contrast to unilateral lesions, equivalent bilateral posterior hippocampal lesions abolished the normal 17-OHCS stress response. These observations support the thesis that the elevated 17-OHCS levels in response to the conditioning paradigm is dependent on the hippocampus. Furthermore, it is dependent upon the continuity of the hippocampal circuit and not upon the volumetric steroid binding capacity of the hippocampus. These studies also suggest that a unilaterally functioning hippocampus may be adequate to meet the physiologic needs of stress, as reflected by the 17-OHCS response.

The effect of psychoactive drugs on plasma corticosterone levels and behaviour in the bulbectomised rat

Bilateral olfactory bulbectomy (OB) in the rat produces a rise in circulating 11-hydroxycorticosterone (11-OHCS) to intermediate levels (40–50 μg/100 ml plasma). Following footshock extreme corticosterone elevation occurs (65–80 μg/100 ml plasma). Bulbectomy also produces behavioural changes which include hyper-reactivity and an acquisition deficit in a step-down passive avoidance test. Treatment of the bulbectomised rat with amitriptyline (5 and 10 mg/kg), mianserin (5 and 10 mg/kg) and viloxazine (2 and 5 mg/kg) administered IP for at least 7 days corrected the acquisition deficit, reduced the hyper-reactivity and the elevated corticosterone levels in a reproducible manner. This reduction in 11-OHCS concentrations occurred in bulbectomised rats with and without footshock. In contrast, the antidepressant drugs did not produce these changes in sham-operated controls (SO). The central stimulant, amphetamine (1 and 3 mg/kg/day for 7 days, IP), increased 11-OHCS concentrations in unstressed OB and SO rats. There was no further elevation in the 11-OHCS concentrations of stressed rats of both OB and SO groups. This drug further impaired the acquisition of both OB and SO rats and increased the reactivity scoring of both groups. The major tranquillizer, chlorpromazine (1 and 3 mg/kg IP for 7 days), reduced plasma 11-OHCS levels and the hyperreactivity of both OB and SO groups. It did not reduce the acquisition deficit exhibited by the OB rats. Chlordiazepoxide (5 and 15 mg/kg IP for 7 days), had a profile similar to that of chlorpromazine except that it impaired acquisition in the SO group. Thus using the techniques described above it is possible to separate the antidepressants from other major classes of psychotropic drugs.

Changes of maternal and fetal pituitary-adrenocortical functions during human labour.

The results of maternal 11-hydroxycorticoid (11-OHCS) determination on blood obtained from four stages of 44 spontaneous labour cases showed a strong and time-related maternal adrenocortical activation during vaginal delivery. The high 11-OHCS level in the cord blood and the increase of the 11-OHCS concentration in the amniotic fluid suggested the same response of the fetal adrenal. However, in 14 cases of elective caesarean sections the 11-OHCS levels in the cord blood and the amniotic fluid did not rise in spite of the elevated maternal plasma 11-OHCS content.

The Effects of Electric Stress on Pancreatic B Cell Function in Rats Fed a High Fat Diet (I)

The synergistic effects of dietary obesity produced by the feeding of a high fat diet and stress induced by electric shocks on glucose tolerance and glucose-induced insulin release from the perfused pancreas were investigated. Male Wistar rats weighing 90 approximately 100 g were fed ad libitum for 12 weeks either a control (50% Starch; C) or a high fat diet (40% Butter; F). Some of the rats on both diets received 100 electric shocks of 1 sec. duration in the stress session for 1 hour per day for the last 3 weeks of the experimental period. Low stress (LS) groups were shocked at a fixed time (Inter Shock Interval: 36 sec.). High stress (HS) groups were shocked at random (ISI: mean = 36 sec, 9 approximately 108 sec. variable). Non-stress (NS) groups were not given any shocks. Rats were killed at 24 hours after the final stress session. Under NS conditions, rats in the F-NS group gained a significant amount of weight and had normal levels of fasting plasma glucose and insulin but an impaired glucose tolerance (k = 3.49). Insulin release from the perfused pancreas in the F-NS group showed a delay in the initiation of release by the stimulation of glucose (16.7 mM), but the total amounts of insulin released did not differ from that in the C-NS group. On the other hand, the levels of plasma 11-OHCS in the fed state were much more highly elevated in the HS group than in the LS group, which was not influenced by the high fat diet. The fasting levels of plasma glucose in the F-HS group (121 +/- 7 mg/100 microliter) were significantly higher than those in the C-HS group (101 +/- 7 mg/100 microliter) in spite of a normal insulin concentration in plasma. In contrast to the normal glucose tolerance in the C-HS group (k = 5.14), glucose tolerance in the F-HS group (k = 3.04) was impaired. Insulin release from the perfused pancreas in response to glucose in both diet group was not significantly altered under LS conditions. In the C-HS group, however, the total amount of insulin released in the second phase was enhanced to 165% of that in the C-NC group. Conversely, in the F-HS group the total amount of insulin released in the first phase was significantly decreased to 40% of that in the F-NS group. These findings indicate that the elevation of plasma 11-OHCS levels provoked by shocks at random rather than in a fixed time schedule is caused by the difficulty in predicting shocks, and a chronic stress induced by electric shocks at random further impairs glucose tolerance and suppresses glucose-induced insulin release in rats fed a high fat diet.

Free Plasma 11-Hydroxycorticosteroids and the Response to β1β24-Corticotrophin in Regular Haemodialysis Patients

The adrenocortical function of 59 patients on regular hemodialysis treatment was tested on 105 occasions by measuring the 30-min response of free plasma 11-hydroxycorticosteroids (11-OHCS) after intramuscular injection of 0.25 mg Synacthen (beta1-24-corticotrophin). The morning basal levels of 11-OHCS were within the normal range. The increase of 11-OHCS after injection of Synacthen was less than normal in 25% of the patients. In 9 patients with a low response an extended Synacthen test was performed. This caused a normal increase in plasma 11-OHCS but the response came later than in normal persons. After 0.25 mg Synacthen intramuscularly the 30-min response of 11-OHCS seemed to be lower on the first day than on the second day after dialysis. The present study supports the view that the pituitary-adrenocortical system is essentially intact in patients on regular hemodialysis treatment.

Central catecholamine and peripheral noradrenaline depletion by 6-hydroxydopamine and active avoidance learning in rats.

Three experiments are reported on the relation among catecholamine (CA) depletion, plasma corticosterone (11-OHCS) levels, and active aversive learning. A baseline study showed no significant relation beteen resting levels of 11-OHCS and central and/or peripheral CA depletion. On a two-way avoidance learning task, depletion of brain CAs produced a widespread learning deficit. When both central and peripheral CAs were depleted, only escape learning emerged. Similar effects occurred on a one-way task, but differences were not so marked. The findings are discussed in terms of a theory of CA-dependent cues.

Elevated serum lactic dehydrogenase activity in patients with cushing's syndrome.

Serum LDH activity was found to be elevated in 16 out of 20 patients with Cushing's syndrome. This elevation was mainly due to increased LDH1 and LDH2, and correlated with the levels of urinary 17OHCS. When the glucocorticoid excess was corrected by surgery, elevated serum LDH levels tended to be normal. Thus, it was concluded that elevated serum LDH is a common finding in Cushing's syndrome and glucocorticoid excess may cause tl-e elevation of LDH by some undetermined mechanism.

Endocrine function in postoperative patients with anterior communicating aneurysm (author's transl)

To evaluate the hypothalamo-hypophyseal function after surgery of the ruptured anterior communicating aneurysm, the reserve of adenohypophyseal hormones (GH, ACTH, TSH, Prolactin, LH and FSH) was determined in 30 patients who had undergone microsurgical procedures. GH was studied during the insulininduced hypoglycemia. The LH, FSH, and TSH reserve was studied by means of LH-RH and TRH administration. ACTH-cortisol axis was evaluated by determining urinary 17-OHCS and serum cortisol levels. These 30 patients were divided into 3 groups based on their preoperative state of consciousness; Group A: fully alert (Grade I of Bottrell's classification, 15 cases), Group B: mildly impaired (Grade II, 10 cases) and Group C: severely damaged (Grade III to V, 5 cases). In 12 of 30 cases GH secretion was found impaired after surgery, but TSH, LH and FSH secretion were impaired only in 4 cases. Seven out of 13 cases in Group A and B had endocrine dysfunction within 3 months after subarachnoid hemorrhage (SAH) and only one of 12 cases had it thereafter. On the contrary, 2 of 5 cases in Group C was examined later than 6 months and both of them had impaired function. GH secretion was impaired in 2 out of 6 cases who had transient postoperative deterioration of consciousness and not in the other 4 cases, suggesting that the influence of microsurgical procedures on endocrine function may be slight. The hypersecretion of TSH, LH and FSH was observed in 11 out of 25 cases in Group A and B with or without impairment of other hormone secretion. None of them had hypothyroidism or hypogonadism clinically and thyroid hormone secretion was found increased in 2 cases. Morning resting levels of serum cortisol determined in 10 cases showed higher levels in 4 cases within 5 weeks after SAH and normal levels in 6 cases after 8 weeks. The pre and post-operative dexamethasone therapy did not suppress serum cortisol levels in the early phase after SAH. These data suggest that the postoperative endocrine disorders may be reversible in the state of mild impairment of consciousness and irreversible in the severely impaired state. In the former state the transient hypothalamic hyperfunction may also occur.