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Abstract
To investigate the role of cortisol in the etiology of insulin resistance in men and women, we examined 218 healthy non-hospitalized elderly, selected from the Rotterdam Study. Free cortisol was assessed by the ratio of fasting serum cortisol over corticosteroid-binding globulin (CBG), and insulin resistance was estimated by the fasting insulin level. CBG was higher in women and decreased with age. In both men and women, the early morning free cortisol level showed no association with age or waist/hip ratio. In men, an inverse association between cortisol and body mass index was observed. In women, higher cortisol levels were associated with increased insulin levels; an increase of 9·7 mU/l insulin per unit cortisol/CBG (s.e. 3·9, P=0·01). The association did not change after adjustment for age, body mass index or waist/hip ratio. The results of this study in elderly subjects suggest that in women cortisol may be implicated in the age-associated insulin resistance.
Journal of Endocrinology (1996) 149, 313–318
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ABSTRACT
Preparations of head kidney tissue (containing the interrenal cells) from brook charr (Salvelinusfontinalis) which had been held at a high stocking density (120 kg/m3) showed a higher spontaneous secretion rate of cortisol than those from brook charr held at a low stocking density (30 kg/m3). Challenges with ACTH at 5 and 500 mU/ml stimulated the secretion of cortisol in interrenal preparations taken from fish stocked at low density but the high ACTH challenge resulted in a lower cortisol secretion rate. The ACTH-stimulated cortisol secretion by the interrenal cells of brook charr stocked at high density was lower than that of the low density group.
There was no difference in the metabolic clearance rate of cortisol in brook charr held at the two stocking densities. The clearance rate of [3H]cortisol from the tissues suggested that in fish held at high stocking density cortisol is rapidly taken up by the liver and subsequently catabolized. Cortisol uptake by the liver in fish held at high stocking density may be an adaptation, which results in altered hepatic metabolic activity.
Journal of Endocrinology (1990) 124, 311–318
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Cortisol metabolism was studied in conscious adult male guinea-pigs subjected to a neurotrophic stress (immobilization and stimulation by light for 3 h).
The disappearance curves of tracer quantities of [3H]cortisol were represented by a two-pool model. In stressed animals, there was a marked increase in the mean plasma level of cortisol (184% of control value; P <0·001) and in the metabolic clearance rate (MCR; 17% of control value; 0·001 <P <0·01). This rise in the MCR of plasma cortisol resulted from an increase in the mean total apparent volume of distribution (49%, P < 0·001). The lack of significant differences in the slopes of the second exponential phase of the disappearance curves indicated that the stress did not significantly increase the half-life of cortisol. The mean binding capacity of transcortin for cortisol (ST) was significantly higher in the animals which had been subjected to the neurotrophic stress than in the control guinea-pigs (0·02 < P <0·05). However, ST values remained very low and accounted for the very high levels of free cortisol found after the stress. The results suggest that the raised concentrations of unbound cortisol found in the plasma of conscious adult male guinea-pigs in response to neurotrophic stress reflect a hypersecretion of corticosteroid.
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Daily blood samples from four mares were assayed for cortisol through a total of eight ovulatory cycles. Mean cortisol concentrations on days −14, −13, −10, −9 and −8 before ovulation (dioestrus) were greater than on days −5 to −1 (oestrus). The highest mean (±s.e.m.) value of cortisol occurred on day − 10 (260± 28 nmol/l) and the lowest on day −2 (142 ±14 nmol/l). A single episode on a day in late dioestrus characterized the maximum cortisol value per cycle for five of eight cycles. Extraction of plasma samples with petroleum ether or chromatography before assay, to eliminate interference from progesterone and its metabolites, did not alter the pattern of high dioestrous and low oestrous cortisol concentrations. Maximum follicular diameter at ovulation was negatively correlated with mean cortisol concentration for that cycle. These results indicate that in the mare the adrenals secrete cortisol more actively during dioestrus than during oestrus and suggest that a decline in cortisol values at oestrus may favour full follicular growth and ovulation.
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SUMMARY
The concentration of cortisol in peripheral plasma (μg./100 ml.) was 0·6 ± 0·1 (s.e.) in penned sheep accustomed to handling and 1·1 ± 0·2 in untrained grazing sheep, or about 1/10 of the basal level in man or the guinea-pig. Plasma cortisol in the goat (mean 1·2) and the ox (2·6 ± 0·3) was also low.
Freely diffusible cortisol was distinguished from protein-bound hormone by gel filtration after equilibration of the plasma with 3H- or 14C-labelled steroid. The binding capacity (μg./100 ml.) of sheep plasma for cortisol at room temp. (1·7 ± 0·2) was only slightly above that of 5% ovine albumin solutions. It compared with 3·5 (2·2–4·6) in the goat, 6·1 ± 1·0 in the ox, 14–21 in the guinea-pig, 17–23 in normal human and 25–59 in human pregnancy plasma. These are minimal estimates, since partial dissociation of the transcortin-cortisol complex occurred under the test conditions. Sheep plasma showed no significant elevation in cortisol concentration or binding power during pregnancy, nor in response to oestrogen administration.
At physiological cortisol levels and room temperature, 39 ± 5% of the cortisol in sheep plasma was protein bound, but values above 40% were associated with low plasma cortisol levels and hence confined to samples from trained or adrenalectomized sheep. ACTH administration or addition of very small amounts of cortisol to ovine plasma in vitro caused a sharp fall in this percentage. Moreover, at body temperature only 9 ± 2% of the plasma cortisol in the sheep was non-diffusible. This finding may account for the great sensitivity of target tissues to the changes of blood cortisol level in this species. In human pregnancy plasma 86–95% of plasma cortisol (> 14μg./100 ml.) was bound at room temperature and 60–74% at 37°.
Published data and those now presented suggest that plasma level and biological half-life of cortisol in different animal species are directly related to binding capacity.
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When hamster adrenal tissue is incubated in Krebs—Ringer solution, cortisone is the major steroid product both from endogenous precursors and from added [4-14C]progesterone (Whitehouse, Vinson & Janssens, 1966, 1967); added radioactive cortisol is rapidly converted into cortisone by hamster adrenal tissue in vitro although cortisol appears to be the main hormonal steroid of the adrenal venous blood. Whole blood of the hamster shows some capacity to reduce cortisone to cortisol, but this seems insufficient to account for the relatively lower yields of cortisone obtained when adrenal tissue is incubated with [4-14C]progesterone in hamster whole blood. Consequently it may be assumed that the function of the adrenal enzymes is modified by factors in the blood.
The metabolic pathway of progesterone involves the stages: progesterone → (intermediates) → cortisol → cortisone, and hence it is possible that the relative amounts of labelled cortisol and cortisone change throughout the
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SUMMARY
Whole body metabolic clearance rates (MCR) and splanchnic, hepatic and renal clearance rates of cortisol were estimated in six shorn sheep under control conditions. The measurements were repeated in the same animals when they were exposed to a cold, wet environment while they were maintaining a normal rectal temperature and again when they became hypothermic, their mean final rectal temperature ( ~ 36 °C) having been reduced approximately 2–3 °C below the control range. The quantitative changes in MCR that occurred during cold stress were found to be associated with corresponding changes in splanchnic and renal clearance rates. Increases in plasma cortisol concentrations up to 50 μg/1 were accompanied by proportional increases in rates of splanchnic blood flow and cortisol clearance. When cortisol concentrations rose above 50 μg/1 in hypothermic animals the MCR values tended to fall because of reductions in hepatic and renal blood flow; very large increases in plasma cortisol concentrations then resulted from comparatively small increases in production rate.
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SUMMARY
Concentrations of cortisol, corticosterone and cortisone in the plasma and adrenal glands, liver glycogen and plasma glucose of foetal, newborn and mother guinea-pigs were estimated during the last 6 days of pregnancy and throughout the first 24 h post partum. At the same time progesterone was measured in the plasma of the mother. During the prepartum rise in foetal plasma cortisol levels and liver glycogen, no significant change in the foetal adrenal cortisol content was observed. The plasma and adrenal cortisol concentrations of the mother were much higher than those observed in the foetus and increased significantly before parturition. In the mother as in the foetus, cortisone and corticosterone represent only a small percentage of corticosteroids compared with cortisol. These results indicate that the autonomous capacity of foetal adrenals, inhibited by maternal secretions before term, appears suddenly at birth.
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SUMMARY
Plasma cortisol concentrations, measured by competitive protein-binding, were examined in intact and hypophysectomized goldfish (Carassius auratus L.) adapted to fresh water or to 210 mm-sodium chloride solutions. The mean plasma cortisol concentration of freshwater-adapted fish (6·6 ± 1·8 (s.e.m.) μg/100 ml plasma) increased after stress and intraperitoneal injections of mammalian corticotrophin. Hypophysectomy resulted in a reduction in plasma cortisol concentration to about 2 μg/100 ml plasma.
Transfer of fish to sodium chloride solutions caused rapid, but transitory increases in the plasma cortisol concentrations in intact, but not in hypophysectomized fish. After 3 days in the sodium chloride solution the cortisol levels were similar to those of control fish kept in fresh water. The plasma concentrations of this corticosteroid in goldfish appear to be unrelated to external salinity, although a 'mineralocorticoid' action of the hormone cannot be excluded.
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SUMMARY
Although cortisol slightly inhibited the incorporation of 2-14C]glycine into the proteins of rat skin samples incubated in vitro, addition of the hormone to the storage medium had a marked protective effect on protein and DNA metabolism. The incorporation of [2-14C]glycine into the proteins, and to a lesser degree that of [6-3H]thymidine into DNA, were stimulated when the incubated skin had been exposed to cortisol during storage. The skin samples stored in buffer containing cortisol transported α-aminoisobutyric acid more effectively; this was concluded to be due to a stabilizing effect of cortisol on the cell membrane. During storage protein catabolism and possibly protein turnover were stimulated by cortisol.
