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H. SELYE
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SUMMARY

Using a modification of the granuloma pouch technique [Selye, 1953], it is demonstrated in rats that pretreatment with somatotrophic hormone (STH) augments the resistance of the adjacent skin to the necrotizing actions of the irritant, while cortisol has an opposite effect. The protective action of STH is abolished by simultaneous cortisol treatment.

It is concluded that, under suitable conditions, the ability of a chemical irritant to produce tissue necrosis can be altered at will by administering varying proportions of STH and cortisol.

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W. J. FULKERSON
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B. Y. TANG
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Three Merino ewes, adapted for about 3 weeks to their environment, were bled at 10 min intervals through a jugular venous cannula. Radioimmunoassay of plasma samples for cortisol revealed marked diurnal variations with peak levels just after midnight and lowest values in the afternoon. This rhythm appeared to result from a changing amplitude associated with a distinct ultradian rhythm (frequency 0·8–1·2 cycles/h) in the plasma level of cortisol. Calculation of the daily rate of secretion of cortisol from the hormone profiles gave a mean value of 8·49 mg. Arguments are put forward in favour of this method for obtaining the true rate of secretion of cortisol.

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R. J. FAIRCLOUGH
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G. C. LIGGINS
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Binding of cortisol to plasma proteins was studied in the foetal lamb by equilibrium dialysis at 37 °C. At 122 days of pregnancy the mean level of transcortin expressed as cortisolbinding capacity was 28 ± 6 (s.d.) ng cortisol/ml plasma. During the last 14 days of pregnancy there was a progressive increase in transcortin-binding capacity to 85 ± 14 ng cortisol/ ml plasma. A sharp increase in the concentration of both protein-bound and unbound cortisol was observed over the same period. A rise in the concentration of total cortisol from around 3 to 42 ng/ml was associated with an increase in unbound cortisol from 0·2 to a maximum of 2·1 ng/ml. The concentration of albumin-bound cortisol was approximately equal to that of unbound cortisol. The mean value for the transcortin–cortisol affinity constant was 1·15 × 108 l/mol.

It is concluded that an increase in transcortin-binding capacity is partly responsible for the prepartum increase of corticosteroid levels observed in normal foetal lambs.

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E. H. D. CAMERON
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M. A. BEYNON
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K. GRIFFITHS
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The ability of cells from the zona fasciculata and the zona reticularis of the human adrenal cortex to transform labelled pregnenolone and progesterone to cortisol in vitro was investigated. Examination of the 3H:14C ratios of 16α-hydroxyprogesterone, 17α-hydroxyprogesterone, 11-deoxycorticosterone and cortisol formed during incubations in vitro suggested that the role of progesterone in the transformation of pregnenolone to cortisol might be a relatively minor one.

An attempt was subsequently made to estimate the relative importance of the biosynthetic pathway to cortisol by way of progesterone in hyperplastic adrenal tissue by a mathematical approach.

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J. Y. F. PATERSON
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J. L. LINZELL
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In pregnant and in lactating goats the rate of cortisol secretion was measured by continuous intravenous infusion of tritium-labelled cortisol. Uptake of cortisol by the mammary gland was measured by simultaneous sampling of blood from the carotid artery and superficial epigastric vein, and measurement of mammary blood flow. In pregnant goats the rate of cortisol secretion was 9 μg/min but in preparturient and in lactating goats the rate was about 32 μg/min. There was a small but significant difference in cortisol concentration between the carotid artery and mammary vein. In pregnant goats the mammary uptake of cortisol was about 0·2 μg/min; this was increased to about 1·3 μg/min in preparturient and in lactating animals. Negligible quantities of cortisol were secreted in the milk.

Cortisol was administered by continuous infusion for 4 h into two lactating goats. Although there was some stimulation of milk secretion it seems likely that it resulted from a systemic rather than local action of cortisol.

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J. D. FEW
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Concentration and specific activity of plasma cortisol were measured for 4 h after the intravenous injection of 10 μCi [1,2-3H]cortisol into 14 normal men. Of these subjects four were resting controls; four exercised at a high work load for 1 h; four exercised at a low work load for 1 h and two received infusions of unlabelled cortisol, all beginning 1 h after the administration of [1,2-3H]cortisol.

In the high work load group plasma cortisol had increased by 12·2 ± 6·3 μg/100 ml at the 60th minute of exercise. In this group the half-life of [3H]cortisol was 31·5 ± 5·3 (s.d.) min in contrast to 74·5 ± 8·3 min for the resting controls (P < 0·001).

In the light exercise group plasma cortisol concentration tended to fall, but due to large intersubject differences this was not statistically significant. In this group the half life (t½) of [3H]cortisol was 43·8 ± 3·9 min which was also significantly different from that of the resting controls (P < 0·001).

Specific activity of plasma cortisol fell rapidly (mean t½ = 15 min) during 1 h of heavy exercise, and continued to fall to a nadir 10–30 min after exercise had ceased, finally reaching a value some 60% above the nadir 1·5–2·0 h after exercise had ceased. A similar, although exaggerated, pattern was observed in the two resting subjects into whom 5 and 4 mg respectively, of unlabelled cortisol were infused. In contrast, in the light exercise group cortisol specific activity changed only slowly (mean t½ = 151 min) but continued to fall after exercise.

In the light exercise group, during the latter part of exercise and during the first hour after exercise, the ratio [3H]cortisone: [3H]cortisol in plasma was significantly higher than the corresponding values for the resting group (P < 0·05). Even higher values for this ratio were obtained for some of the heavy exercise subjects but due to wide scatter the group was not statistically significantly different from the resting group.

These results suggest that exercise itself increases the rate of uptake of cortisol by peripheral tissues and that when the work load exceeds a critical level stimulation of the adrenal cortex results in a massive secretion of cortisol which is sufficient to raise the plasma level which in turn promotes further ingress of cortisol into the tissues. After exercise at a high work load a return of cortisol from the tissues to the plasma can be detected.

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D. A. SHAW
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Specific activities were determined for cortisol and its metabolites isolated from several successive urine samples collected from patients who had each received a single injection of a tracer dose of [4-14C]cortisol. Some theoretical aspects of the curves relating specific activity to time after injection are considered.

Evidence is presented and discussed for an alternative route to the 11-oxygenated 17-oxosteroid metabolites of cortisol probably involving not an initial reduction of the ring A of cortisol but a simultaneous cleavage of the side-chain at C-17 of the steroid nucleus and reduction of ring A.

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E.M. Wintour
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J.P. Coghlan
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M. Towstoless
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ABSTRACT

Cortisol was infused, intravenously, for 4 h continuously into 5 chronically cannulated ovine fetuses at 111-120 days of gestation (term is 142-152 days). The dose used was 100 μg/h, and raised fetal blood cortisol concentrations from 8.2±4.0 to 56.5±19.0 nmol/l (values are mean ± SEM). The effects observed were 1) a 4-5 fold increase in sodium and chloride excretion, 2) a doubling of potassium excretion and free water clearance, 3) no significant changes in urine pH, urea and creatinine excretions, and 4) an increase in urine osmolality from 129±7.5 to 154.4±11.3 mosmol/kg water. There were no significant changes in any of the measured parameters in 5 fetuses infused with 0.9% NaCl for 4 h. It is suggested that the hyponatremia and inability to retain sodium observed in many premature or very low birth weight babies may be due to the fact that their kidneys are behaving as fetal rather than neonatal organs and responding to the high plasma cortisol concentrations found in such babies with a natriuresis.

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J. Grinblat
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A. Klein
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A study was carried out to determine the effect on lymphocytic cortisol metabolism (LCM) of plasma from 62 patients with diffuse thyrotoxic goitre (DTG), 14 patients with toxic nodular goitre (TNG) and ten hypothyroid patients. Plasma of 33 healthy donors served as controls. A known concentration of human lymphocytes was incubated with cortisol in media containing 50% phosphate-buffered saline (PBS) and 50% of one of the following additions: (1) PBS, (2) homologous plasma (HP), (3) heterologous plasma, (4) plasma from DTG patients, (5) plasma from TNG patients, (6) plasma from hypothyroid patients, (7) PBS and HP to which l-thyroxine (T4) and tri-iodothyronine (T3) had been added separately and as a mixture up to a concentration ten times the normal, (8) boiled HP and (9) boiled DTG plasma. Plasma from hypothyroid patients gave an LCM-enhancing effect (LCMEE) similar to that of HP. The plasma of DTG and TNG patients had a markedly lesser effect on LCM than did HP. The T4 and T3 had no additional effect when added to PBS or HP. Boiling of HP and DTG plasma resulted in a similar decrease in LCMEE. The findings of this study raise the possibility of the existence of a factor inhibiting LCMEE in the plasma of thyrotoxic patients.

J. Endocr. 1984 101, 149–153

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J. Y. F. PATERSON
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J. L. LINZELL
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SUMMARY

Glucose entry rate was measured by primed infusion of [2-3H]glucose, and cortisol secretion rate by infusion of [1,2-3H2]cortisol, in two cows from 142 days before calving to day 287 of lactation. Mammary blood flow and the mammary uptake of glucose and cortisol were also measured.

In late pregnancy, cortisol secretion rate was 8·6 ± 3·17 (s.d.) μg/min and plasma cortisol concentration was 1·8 ± 0·52 μg/l. During parturition in one animal the secretion rate was 92 μg/min and plasma cortisol concentration was 15 μg/l. During lactation the secretion rate (26·4 ± 7·14 μg/min) and plasma cortisol concentration (5·6 ± 0·73 μg/l) were significantly greater than in dry cows. The mammary uptake of cortisol was 3 to 4% of the secretion rate in both dry and lactating cows.

Glucose entry rate was 5·77 ± 2·250 (s.d.) mg/min/kg0·75 in dry cows and there was no significant mammary uptake of glucose. During lactation the glucose entry increased to 9·45 ± 1·881 mg/min/kg0·75. Mammary uptake of glucose was 3·56 ± 1·949 mg/min/kg0·75. The non-mammary utilization of glucose, glucose entry less mammary uptake, was the same for dry and lactating cows.

There was a good correlation between glucose entry and milk yield, and between mammary uptake of glucose and milk yield. Since the mammary arterio-venous glucose concentration difference was relatively constant, it is suggested that the change in mammary blood flow may determine the change in glucose uptake and milk yield.

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