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SUMMARY
The metabolism and the rate of transfer of cortisol across the placenta in pregnant guinea-pigs and foetuses were studied by constant intravenous infusions of tritium-labelled cortisol. Estimates of endogenous and radioactive plasma cortisol levels were used to calculate the following parameters at four stages before parturition (days 62, 64, 66 and 67; parturition occurring at day 68): metabolic clearance rate; production rate; adrenal secretory rate; transfer rate from mother to foetus and from foetus to mother; irreversible removal rate; the fraction of cortisol derived from the other in the foetal and maternal vascular compartments; the fraction of secreted and recycled cortisol involved in the transfer. The metabolic clearance rate and the rates of production and secretion of cortisol were higher in the mother than in the foetus between days 62 and 67 of gestation. About 90% of the foetal cortisol was of maternal origin. The fraction of maternal cortisol of foetal origin increased in the last days of gestation.
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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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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
Concentrations of cortisol and corticosterone in the plasma and adrenal glands of male and female guinea-pigs were estimated throughout the first postnatal day and thereafter at intervals up to 3 weeks of age. In the guinea-pig, the basal level of cortisol secretion is established more slowly than in other species. The concentration of plasma cortisol is very high at birth, with a marked fall between days 1 and 10 post partum and then a steady level from day 10 to 20, the time of weaning. At day 10 the values for plasma cortisol and corticosterone approach the lower ones found in the adult. There were peaks in the amounts of corticosteroids found in the adrenal gland at 50 h, 4 and 7 days and these may have been due to increased hormonal synthesis between days 2 and 8.
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To evaluate the role of the liver in cortisol catabolism the extraction ratio of both cortisol and cortisone by the organs of the splanchnic area was estimated in guinea-pigs anaesthetized with pentobarbitone. The [3H]cortisol and [3H]cortisone concentrations were measured in portal and sus hepatic venous plasma during a constant infusion of [3H]cortisol or [3H]cortisone. The extraction ratio of cortisol was estimated to be 10–14% in the splanchnic area and the viscera, while in the liver it had a small negative value suggesting that the liver had produced as much or more cortisol than it had taken up. All the cortisone (95%) formed from cortisol in the viscera was eliminated from the plasma compartment by the liver. Some 75–80% of the infused cortisone was converted to cortisol; rather less of the infused cortisol was converted to cortisone (32%). Using estimates of plasma flow derived from sham-operated animals, the uptake of cortisol by the various organs was calculated. The splanchnic area extracted 41% of the infused cortisol from the plasma: 25–27% as cortisol and 13–16% as cortisone. The liver appeared to take up cortisone preferentially. The conversion of cortisone into cortisol within the liver seems to be important in limiting the amount of cortisol removed from the plasma by the splanchnic area. The liver is also important in inactivating the steroids although other sites are probably also involved.
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The concentrations of corticosterone and aldosterone in the plasma and adrenal glands of foetal, newborn and mother mice were estimated during the last 4 days of pregnancy and throughout the perinatal period. The level of corticosterone in the maternal and foetal plasma fell from day 17 of gestation until birth, and then remained stable. Whereas the corticosterone content of the maternal adrenal glands did not change significantly, that of the foetal adrenal glands reached a peak on day 19 of gestation. At every stage of gestation, the level of corticosterone in the maternal plasma was higher than that in the foetus. Changes in the concentration of aldosterone in the foetal plasma and adrenal glands were similar and characterized by peak values at birth. In the mother during the last 4 days of pregnancy, the level of aldosterone in the plasma was higher than in non-pregnant mice, but lower than that in the foetus.
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Sexual dimorphism in adrenal activity appeared during the pubertal period of the guinea-pig with plasma levels and binding of cortisol lower in male guinea-pigs compared with female, and metabolic clearance rate (MCR) of cortisol higher in male than in female animals. Gonadectomy of female guinea-pigs did not change the values of the parameters regulating adrenal activity. Castration of male guinea-pigs caused a rise in plasma cortisol levels by increasing the binding capacity of transcortin for cortisol and by decreasing cortisol MCR. Treatment of females with testosterone from day 24 produced a drop on day 50 in plasma cortisol levels following a decreased binding capacity of transcortin for cortisol and at the same time as cortisol MCR increased. Furthermore, the adrenal response to stress was higher in castrated than in control males and lower in testosterone-treated females compared with control females. Testosterone appeared to be the hormone responsible for sexual dimorphism in adrenal activity in the pubertal guinea-pig.
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The metabolic clearance rate and the binding of cortisol in plasma of male and female guinea-pigs were estimated at five stages between birth and weaning. The metabolic clearance rate for cortisol remained low in both sexes until day 10 post partum but increased to adult values by day 20. The level of free cortisol in plasma and the cortisol binding capacity of the plasma were higher at birth than on day 10 post partum; the values found on day 20 were similar to those of the adult guinea-pig. Surgical stress increased levels of cortisol in plasma on day 20 but not at birth.
