17-OHCS Concentration Research Articles

Concurrent hypersecretion of aldosterone and cortisol from the adrenal cortical adenoma

Hypertension, hypokalemia, suppressed plasma renin activity and increased plasma aldosterone were found in a middle-aged woman. Following removal of the tumor in the left adrenal gland these abnormalities disappeared. Concurrently, however, the plasma cortisol level did not show normal diurnal change, although the value at 6 A.M. was within the normal range. Administration of 2 mg dexamethasone failed to depress the plasma cortisol level and urinary 17-OHCS concentration. Postoperatively, plasma cortisol and urinary 17-OHCS were below normal. Histologic examination of the tumor indicated the presence of two types of adenoma cells; one was a large watery clear cell with rich lipid and possibly with aldosterone secretion and the other was an acidophilic cell with poor lipid and possibly with cortisol secretion. It is suggested that, in addition to oversecretion of aldosterone, the tumor autonomously secreted cortisol, although the amount of cortisol secreted was not large enough to produce typical Cushing's syndrome.

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.

Pituitary adrenocortical response to noise exposure in rats.

Male rats were exposed to the wide octave-band noise for eight hours at the intensity of 60, 80, or 100dB (C), respectively. The 11-OHCS concentration in the adrenal glands increased in the initial stage of noise exposure, and returned to the control level soon after. The circadian rhythm of 11-OHCS remained in spite of the continuation of noise exposure except in the initial response. After the noise exposure, rats were exposed again at 100dB (C). The 11-OHCS did not increase in the rats exposed previously at 100dB (C). In all the intensities, the 11-OHCS increased to the control level by ACTH administration at the end of noise exposure. By histamine administration at the end of noise exposure, the increase of the 11-OHCS was less in the rats exposed to 100dB (C) than in the rats exposed to low intensities.

New method of obtaining cinchophen ulcer in dogs.

Cinchophen injected into the cerebral ventricle reacted with the hypothalamus somewhere in the vicinity ventricle, and produced a release of ACTH as indicated by a rise in peripheral plasma 11-OHCS concentration in the dog. The amount of cinchophen injected into the ventricle corresponds to about 1/600 of the dose required to produce the same effect by the intravenous route. Repeated intraventricular injections of cinchophen were effective in producing gastric erosions and ulcers at smaller doses than the intravenous one (1/100 and 1/400). Damage to the gastric wall might be due to a mechanism involving a localized portion of the hypothalamus and/or via a cerebral ventricle. Bilateral truncal vagotomy did not have any effect on chronic ulcer production. The cinchophen ulcerations were accompanied by an increase in plasma corticosteroids. The new experimental technique for producing peptic ulcer in dogs via a central neurohumoral mechanism is described.

Effect of an Oral Contraceptive on the Lysine-8-Vasopressin Test in the Diagnostic Evaluation of Pituitary Function

A comparative study was performed on the plasma 11-hydroxycorticosteroids (11-OHCS) responses to lysine-8-vasopressin (LVP) before and during ingestion of an oral contraceptive wieh oestrogenic activity. A total of 19 healthy women with a normal menstrual cycle and normal plasma 11-OHCS content in blood samples at 8 a.m. and 4 p.m. were included in the study. The results show that the mean response of plasma 11-OHCS to the administration of LVP was equal in magnitude before and during ingestion of the contraceptive, although the baseline value of 11-OHCS doubled as a result of the treatment. On the other hand, during contraceptive treatment the increase of plasma 11-OHCS concentration after the administration of LVP was somewhat slower, reaching its peak later than before treatment. The noticeable variation in individual responses of plasma 11-OHCS to LVP increased during the treatment. Three subjects showed weak responses to LVP, although the adrenocortical responses to exogenous ACTH were quite normal. The inidvidual responses to LVP before and during ingestion of an oral contraceptive with oestrogenic activity are discussed.

トルエン暴露時の間脳-下垂体-副腎皮質系の反応に関する実験的研究

Diencephalon-hypohysis-adrenal cortex system is one of the most sensitive systems to harmful evironmental factors and this system has an important role for the organism to exist in the harmful environment. Takeuchi, one of the authors, in the previous experiment, obtained the. results that toluene vapor might effect diencephalon-hypohysis-adrenal cortex system and that the function of this system might decrease in the chronic exposure to toluene.We think in order to make clear toxicity of organic solvents, it is very important to study the response of this system to organic solvents. And we performed the following animal experiments using male rats. As indices of the responce of diencephalon-hypohysis-adrenal cortex system, adrenal weight, 11-OHCS concentration in the blood, eosinophile count of the blood and thymus weight were determined.The results are as follows : 1) In 8 hr exposure to 2000 ppm toluene vapor, adrenal weight and 11-OHCS concentration in the blood of the exposed animal increased significantly and eosinophile count of the blood decreased significantly in comparison with the control. But, 16 hr after the end of exposure, these significant differences were not found.2) In 8 hr exposure to 1000 ppm toluene, adrenal weight and 11-OHCS concentration in the blood of the exposed animals significantly increased and eosinophile count of the blood was significantly smaller in comparison with the control as well. And in 8 hr exposure to 100 ppm toluene, the change of these indices was similar as in the case of 1000 ppm, except adrenal weight which did not significantly increase in comparison with the control. The changes of these indices in 8 hr exposure to 100 ppm toluene were larger than in the case of 100 ppm.3) In the exposure of 8 hr a day for 4 weeks to 1000 ppm toluene, adrenal weight of the exposed animals increased significantly in comparison with the control after 2 weeks and became still larger after 4 weeks. Eosinophile count increased and after 4 weeks it was significantly larger than the control. 11-OHCS concentration in the blood of the exposed animals decreased after 1 week but the difference between the exposed and the control was not found after 2 weeks.After 4 weeks, 11-OHCS concentration in the blood of the exposed animals increased but this increase was statistically not significant in comparison with the control. The reactivity of these indices against the exposure to 1000 ppm toluene chan gedbetween the exposed and the control remarkably after 4 weeks.From the results of these three animal experiments, it was found that the diencephalon-hypohysis-adrenal cortex system responses remarkably against the exposure to toluene vapor, and even in 8 hr exposure to 100 ppm toluene the changes of these indices are found, and in 4 weeks exposure to 1000 ppm toluene, the changes of these indices are cummulative.

Plasma 17-Hydroxycorticosteroid Levels in Healthy and Diarrhoeic Calves

SUMMARY Plasma free 17-hydroxycorticosteroid (17-OHCS) levels of healthy calves of the red-spotted breed varied with age. The highest concentration was found in newborn calves during the first 16 hours of life. The 17-OHCS values observed in diarrhoeic calves also varied with age. However, the 17-OHCS concentration in diarrhoeic calves aged 1–14 days was significantly higher than that of healthy animals of the same age.

Circadian excretory rhythms in night workers.

Conroy, R. T. W. L., Elliott, A. L., and Mills, J. N. (1970).Brit. J. industr. Med.,27, 356-363. Circadian excretory rhythms in night workers. Urine samples have been collected from day and night shift workers in a light engineering factory over periods of 24 or 48 hours during which blood was also collected for determination of plasma 11-hydroxycorticosteroids (11-OHCS). Different subjects divided their 24-hour output into as few as 4 or as many as 14 portions. Where possible, the timing of the excretory rhythms was assessed objectively by fitting a sine curve. The potassium excretory rhythm was, in most subjects, well adapted to night work in that they excreted least during their hours of sleep; no relationship could be discerned between potassium excretory and plasma 11-OHCS rhythms. The sodium excretory rhythm was less regular than that of potassium in both night and day workers, and in night workers both sodium excretion and urine flow were often high during the hours of sleep, so that the subjects were sometimes awakened by the need to micturate. There was, however, sufficient association between the behaviour of sodium and potassium to suggest that their excretory rhythms have a common cause, and that this is not the secretion of 11-OHCS. Phosphate excretion fell sometimes on rising, even though plasma 11-OHCS concentration was not high, and sometimes after a high level of plasma 11-OHCS, at a time other than on rising. This suggests that these are two independent contributory causes of the usual morning fall in phosphate excretion.

Reversed action of acetylated corticotrophin: inhibition of adreno-cortical secretion.

ABSTRACT A derivative of corticotrophin with acetylated amino groups and hydroxyl groups in serine was used. Acetylated corticotrophin significantly decreased the 17-hydroxycorticosteroid (17-OHCS) level in the plasma of guineapigs 4 hours after the i. m. injection of the derivative in a dose equal to 2.5 USP units of the active hormone per 100 g of body weight. The mean plasma 17-OHCS concentration before the injection of the derivative was 44 ± 2.15 μg/100 ml. After the injection of acetylated corticotrophin, the fall in 17-OHCS content was highly significant, the average level being decreased to 61 %. However, in 12 out of 36 animals there was a fall to 30 % of the initial level. The derivative obtained may be considered as an »anahormone«, and probably has the ability to inhibit the secretion of endogenous corticotrophin.

Assessment of pituitary reserve in subjects pretreated with dexamethasone

Plasma 17-OHCS and growth hormone responses to insulin-induced hypoglycemia and Piromen-induced fever have been determined in subjects who were acutely pretreated with dexamethasone. Dexamethasone, in the dosage used, does not interfere with the effect of insulin on the increase in plasma growth hormone or plasma 17-OHCS concentration, provided an adequate amount of insulin is used to produce the same degree of hypoglycemia as when there was no steroid pretreatment. By utilizing the hormonal responses of normal subjects, and patients with hypopituitarism, criteria have been established for classifying responses as normal, abnormal or uninterpretable. An increase in plasma 17-OHCS concentration of 7.5 μ g. 100 ml. or greater following the injection of insulin was considered normal with or without overnight steroid pretreatment. A lesser increase was abnormal if the minimum blood glucose was less than 45 mg. 100 ml. and uninterpretable if the minimum blood glucose was greater than 45 mg. 100 ml. Growth hormone responses to insulin-induced hypoglycemia were similarly interpreted with a normal growth hormone rise being 7.5 mμg./ml. With or without overnight steroid pretreatment, an increase in plasma 17-OHCS concentration of greater than 7.5 μ g. 100 ml. in response to Piromen was considered normal. A lesser response was abnormal if the maximum temperature was 100.5° F or greater, and uninterpretable if the maximum temperature was less. A plasma growth hormone increase of 5 mμg./ml. or greater in response to Piromen was considered normal. A lesser increase was uninterpretable.

Light synchronization of the circadian rhythm in plasma cortisol (17-OHCS) concentration in man.

ABSTRACT In order to determine whether the pituitary-adrenal cycle of normal man is synchronized by the dark-light cycle or by some other phenomenon associated with the sleepwake cycle, normal subjects underwent experimental alteration of their dark-light schedules in such a way that partial dissociation of the darklight schedules from the sleep-wake schedule was achieved. In addition, 3 blind subjects were studied. The normal subjects were allowed several days to become adapted to a given schedule prior to sampling of blood for plasma 17-hydroxycorticosteroid (17-OHCS) determinations. Hourly blood specimens were obtained through indwelling venous catheters in such a manner as to avoid disturbing sleep or exposing the subject to light during dark periods. Each subject slept 8 hr each day from 10 PM till 6 am, and the schedule of meals and activity was identical for all studies; only the dark-light schedule was altered. When the hours of darkness were scheduled in the middle of the waking day, from 10 am u...

Adrenal function and serum protein concentrations in a kindred with decreased corticosteroid-binding globulin (CBG) concentration.

A familial decrease in corticosteroid-binding globulin has been described in a 4-generation kindred. The affected family members are healthy and no specific disease states related to this finding have been found. Other estrogen-responsive serum protein concentrations including thyroxine-binding globulin, ceruloplasmin and haptoglobin were normal. There are no signs or symptoms of clinical hypoor hyperfunction of the adrenal glands. Total plasma 17-OHCS concentration was significantly below normal, but the nonprotein-bound 17-OHCS was in the normal range. A urinary loss of 17-OHCS was not evident. The mode of inheritance is not clear.

Familial decrease in corticosteroid-binding globulin

Despite continuing extensive investigations of the corticosteroid-binding globulin (CBG) in man, to date no reports of a familial alteration in its plasma concentration have appeared. The present report gives information on studies done on 3 generations of a family found to have diminished plasma CBG concentration. CBG concentration in the propositus was 17 mg./L. (normal 23–46 mg./L.), was 17 mg./L. in her mother, 16–20 mg./L. in 2 brothers and 16–17 mg./L. in 2 sisters. Three of 4 members of the third generation were abnormal (15–20 mg./L.). The response of plasma CBG in the propositus to estrogen was subnormal with an increase of only 22 mg./L. following I week of 5 mg. diethylstilbestrol (normal 32–89 mg./L.). Morning plasma 17-OHCS concentration was significantly below normal in affected individuals (mean 6.7 μ g. 100 ml. ), but nonprotein-bound 17-OHCS concentration was normal. Urinary 17-OHCS excretion was 4.2–5.6 mg. 24 hrs. (normal 4–10 mg. 24 hrs. ). The mode of inheritance appeared to be autosomal dominant, and the affected members were healthy, intelligent and prolific.

INFLUENCE OF THE HYPNOTIC TRANCE ON PLASMA 17-HYDROXYCORTICOSTEROID CONCENTRATION.

In a pilot study and a formal experiment, plasma 17-hydroxycorticosteroid concentration was observed to drop to unusually low levels (3 μg./100 ml. or less) at the end of 90 min. of deep, relaxing, hypnotic trance. In the formal experiment on 12 subjects who were very susceptible to hypnosis, the low plasma 17-OHCS levels occurred in 25% of the hypnotic sessions, but only rarely in control periods (p < .0001). This trance-associated phenomenon could not be reproduced consistently in individual subjects, nor was it possible to predict its occurrence from any obvious characteristics of the trance experience. These decreases in 17-OHCS concentration may be related to the tension-relieving or the euphoric aspects of deep hypnosis. It is important to take into account possible physiological effects of the trance per se when evaluating physiological changes during subsequent hypnotic induction of affect.

EXPERIMENTAL AND CLINICAL STUDIES ON ADRENOCORTICAL FUNCTION IN EXTRACORPOREAL CIRCULATION

1. Experimental StudiesNineteen mongrel dogs were used to study the arterial pressure, adrenal venous blood flow, concentration of free 17-OHCS in adrenal venous plasma, secretion of free 17-OHCS in adrenal venous plasma and concentration of free 17-OHCS in peripheral venous plasma in the purpose of exploring the variation of adrenocortical function experimentally.1) Average of adrenal venous blood flow is 6.56 cc/min, and that of 17-OHCS concentration in adrenal-venous-plasma is 197.1 μg/dl before extracorporeal circulation. Secretion of 17-OHCS is 6.25μg/min and the concenraition in peripheral venous plasma is 12.2μg/dl.2) Relationship between arterial blood pressure and adrenal venous blood flow in different kinds of extracorporeal circulation is parallel, when they are observed in normo-and hypothermal perfusion groups.3) Adrenal venous blood flow in normothermal group is inversely proportional to 17-OHCS concentration in adrenal venous plasma, but not in hypothermal group.4) As to secretion of 17-OHCS in adrenal venous plasma, the normothermal group shows the increase of secretion, while hypothermal group shows the decrease which seems to be resulted from the functional inhibition of adrenal cortex.5) Secretion of adrenal gland is directly proportional to 17-OHCS concentration in the peripheral venous plsma.6) Adrenal tissue does not show any remarkable histological changes after perfusion.2.Clinical StudiesAdrenocortical functions of 13 clinical cases in normo-and hypothermal extracorporeal circulation were investigated by estimating of free-17-OHCS concentration in peripheral venous plasma and excretion of 17-OHCS and 17-KS in urine.1) Arterial blood pressure in cold perfusion under 35°C sustains almost constancy, 60mm Hg., while that in warm perfusion shows higher values.2) Though 17-OHCS concentration in plasma during the perfusion decreases markedly in hypothermal group and increase again by warming, hypothermal group shows nothing changeable. Both normo-and hypothermal group show the same postoperative variation curve. Concentration becomes highest 3-6 hours after the operation, then it gradually decrease, and comes back to normal value after 5 days.3) No remarkable difference can be found in 17-OHCS concentration in plasma between Z-uhdi and Kay-cross typed artificial oxygenator.4) Excretion of urinary 17-OHCS has an almost parallel relationship to the postoperative variation of 17 OHCS concentration in plasma. The excretion becomes maxmal in the following day of operation and recovers to normal on the fifth day.5) When excretion of urinary 17-OHCS is observed from viewpoint of perfused volume, low perfused group shows higher excretory value than that in high perfused group. We could not obtain any experimental and clinical evaluation to suggest the adrenal insufficiency.

Subjective and objective measurement of responses to third molar impaction surgery

Clinical criteria, consisting of an appraisal of surgical difficulty and post-operative pain, and chemical criteria, consisting of serum free and urine total 17-OHCS changes, were studied in patients who had undergone the removal of seventy-one mandibular third molar impactions. A significant association was found between surgical difficulty and serum free 17-OHCS concentration in blood specimens both 1 hour (P < .01) and 3 hours (P < .05) postoperatively. No significant association was found between pain experience 3 hours postoperatively and serum free 17-OHCS concentration when the blood samples were drawn 1 hour postoperatively. A significant correlation was found between pain experience 3 hours postoperatively (P < .01). No significant differences in total urine 17-OHCS concentrations were detected when the subjects were grouped according to either surgical difficulty or postoperative pain experience.

PREGNANCY IN CUSHING'S SYNDROME.

Stillborn premature infants were delivered by 2 patients with Cushing's syndrome due to adrenal adenoma. The adrenals of both infants were markedly small due to premature involution of the fetal cortical zones. Although the urinary 17-KS excretion and the plasma 17-OHCS concentration may be increased in uncomplicated pregnancy, absence of diurnal variation of the elevated plasma 17-OHCS and increased urinary excretion of 17-OHCS confirmed the presence of Cushing's syndrome.

Bioassay of ACTH Based on the Plasma 11-hydroxycorticoid Concentration in Hypophysectomized Rats

Bioassay of ACTH based on the rat plasma 11-hydroxycorticoid (11-OHCS) was investigated. The method of Silber et al. (1958) in the extraction process and the method of Zenker and Bernstein (1958) in the fluorescent reaction were used for the determination of 11-OHCS in rat plasma, using corticosterone as the standard. The results are summarized as follows : Both the concentration of plasma 11-OHCS (μg/dl) and the relative adrenal weight (mg per 100g body weight) are inversely proportional to the body weight in the intact rat.The plasma 11-OHCS concentration of intact Wistar male rats weighing 100 to 120g is 40 to 50μg per dl, and it decreases to 5 to 8μg per dl 20 hours after adrenalectomy or hypophysectomy.Plasma 11-OHCS concentration in the adrenal venous blood of the hypophysectomized rat is approximately 16pg per dl. It increases immediately after the intravenous injection of ACTH, 10mU per rat, and reaches the maximum level, about 370μg per dl, at 40 to 50 minutes after the injection.The response of plasma 11-OHCS to ACTH is not only more sensitive but greater than that of adrenal ascorbic acid (AAA). In the dose-response regression, a wider dosage-range is obtained with plasma 11-OHCS than with AAA.The data of a 4-point intravenous, assay on an ACTH preparation against the U.S.P. Reference Standard with a total of 28 rats, providing 0.082 for the lambda value of precision index and 84 to 119% for the confidence limit of the calculated relative potency, indicate satisfactory accuracy of the ACTH assay based on plasma 11-OHCS increase.The pattern of plasma 11-OHCS after a single subcutaneous injection of a long-acting ACTH preparation, 1 U.S.P. Unit per rat, does not coincide well with that of AAA. Both responses are produced almost simultaneously, but the restoration of plasma 11-OHCS response is much faster than that of AAA response. When the same ACTH preparation is injected subcutaneously every two hours with a dosage of 1 U.S.P. Unit per injection, the plasma 11-OHCS keeps the maximal level obtained in the case of a single injection, but AAA gradually decreases with the repetition of ACTH injection below the level obtained by the single injection.The merits of rat plasma 11-OHCS as an indicator of ACTH bioassay are discussed.

On the diurnal variation of adrenal cortex hormones. Comparison of persons with thyroid accelerated diseases and normal persons

For several years, we have studied clinically and experimentally the influence of thyroid hormone on secretory activity of adrenal cortex and cortisol metabolism. In this paper the diurnal rhythm of free and conjugated 17-OHCS in plasma and urine, their clearances and the cortisol half-life in hyperthyroid and normal subjects, will be presented.In hyperthyroid patients there was a completely normal diurnal variation in plasma free and conjugated 17-OHCS concentration, the peak values being found early in the morning and the lowest at midnight (Table 3, Fig.3). Urine samples were collected every four hours during 24 hours. The urinary free 17-OHCS excretion in hyperthyroid patients was greater than in normal subjects for all times of the day, but the magnitude of the diurnal variation in hyperthyoid patents was within normal range (Fig.1 Table 1). The urinary conjugated 17-OHCS excretion in hyperthyroid patients was greater than in normal subjects for all times of the day, and was especially elevated in the morning Fig.2, Table 2). Therefore, the magnitude of diurnal variation in urinary conjugated 17-OHCS excretion hyperthyroid patients was greater than in normal subjects. In order to illustrate this phenomenon, we studied the diurnal variation of renal clearance of 17-OHCS and cortisol half-life after infusion of cortisol in hyperthyoroid patients.Plasma sample were collected at 7.00 a.m. and 0.00 a.m., urine samples were collected during the hours from 6.00 a.m. to 8.00 a.m. and from 11.00 p.m. to 1.00 p.m. The renal clearance of free 17-OHCS was greater in hyperthyroid patients than in normal subjects at 0.00 a.m. and 7.00 a.m., while in both cases there was no diurnal variations in the renal clearance of free 17-OHCS (Fig. 5, Tabl 3).The renal clearance of conjugated 17-OHCS was greater in hyperthyroid patients then in normal subjects in the morning as well as at midnigt, and was especially elevated in the morning (Fig. 5, Table 3).These was no diurnal variation in the renal clearance of conjugated 17-OHCS in normal subjects, but in hyperthyroid patients the diurnal variation was observed (Fig. 5, Table 3.) Increased metabolism of cortisol in hyperthyroid patients was observed in the half-life study of cortisol. The removal rate of infused cortisol (50mg) from the plasma of hyperthyroid patients and normal subjects was measured at 8.00 a.m. and 0.00 a.m. The half-lives of plasma cortisol in normal subjects at 8.00 a.m. and 0.00 a.m. were 117.3 minutes and 115.5 minutes. There was no significant difference between these values. The half-life of plasma cortisol in hyperthyroid patients at 8.00 a.m. was 72.5 minutes ; at 0.00 a.m., 90 minutes. There was a significant difference between these values. Therefore, the diurnal variation in the cortisol half-life was not observed in normal subjects, while it was observed in hyperthyroid patients (Fig.6. Table 4).In summary, the increase of the renal clearance of conjugated 17-OHCS and the cortisol disappearance rate in hyperthyroid patients were greater in the morning than at midnight ; these phenomena were not observed in normal subjects.

Studies of the diurnal variation of plasma 17-hydroxycorticosteroids in man.

Studies are reported of the diurnal variation of plasma 17-OHCS concentration in normal subjects and in patients with various diseases. Only in clinical situations associated with alterations in consciousness or sleep pattern was there significant loss of the diurnal rhythm. The rate of removal of hydrocortisone from the plasma was the same at various times of the day, but the adrenal production of 17-OHCS in response to maximally stimulating doses of ACTH was less at night than at other times during the 24-hour period. Submaximal stimulation of the adrenal cortex with ACTH during the late afternoon and evening restored to normal the nocturnal adrenal response to ACTH. It is suggested that the diurnal variation of plasma 17-OHCS depends on variations in the rate of secretion of ACTH. The change in ACTH secretion apparently is controlled by a central nervous system mechanism of unknown character. Total reversal of sleep and activity in normal subjects results in reversal of the diurnal rhythm in plasma 17-OHCS and serum iron levels, and body temperature.