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Search for other papers by P. A. Robinson in
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ABSTRACT
A monospecific antiserum against human corticosteroid binding globulin (hCBG) has been used to identify structural similarities between hCBG and CBG in the blood of other primates and representative species of different vertebrate classes. Double immunodiffusion analysis indicated that only CBG in Old World monkeys and apes cross-react with the hCBG antiserum. This was confirmed by a solid-phase radioimmunoassay for hCBG which also demonstrated that CBG in apes is immunologically identical to hCBG and that Old World monkey CBG comprises most, but not all, of the hCBG epitopes. The electrophoretic mobilities of human, gorilla and gibbon CBG were similar (R F 0·50–0·51), but differed from Old World monkey CBG (R F 0·44–0·49) and chimpanzee CBG (R F 0·47). Although serum/plasma cortisol binding capacities were similar in Old World primates, the dissociation half-times (t ½) of cortisol were higher from human and ape CBG (18–25 min) than from Old World monkey CBG (14–18 min). The steroid binding specificities of human and ape (CBG corticosterone > cortisol > progesterone ≥ testosterone) were also different from those of Old World monkey CBG (corticosterone >> cortisol ≃ progesterone > testosterone). Lemur plasma cortisol binding capacity and CBG dissociation t ½ of cortisol were similar to hCBG, but its steroid binding specificity was different (cortisol > corticosterone > progesterone ≥ testosterone) and it did not cross-react with the hCBG antiserum. We could not detect high affinity cortisol binding activity in blood samples from New World monkeys, and they did not cross-react with the hCBG antiserum. These results suggest that considerable modification in the steroid binding activity and structure of CBG has occurred since the evolutionary appearance of the primates, but that the rate of change decreased after the cladogenesis of Catarrhine primates.
J. Endocr. (1985) 104, 251–257
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ABSTRACT
A corticosteroid binding globulin variant (CBGv) has been identified in a serum sample taken from an apparently healthy woman during late pregnancy. Identification was based on the observation that it exhibited approximately half the cortisol binding capacity expected when compared to its concentration measured by radioimmunoassay (RIA). Affinity purification of CBGv excluded the possibility that this anomaly was caused by assay interference, and demonstrated that immunoreactive CBGv was capable of binding cortisol. The CBGv had a molecular weight (63 800) similar to normal CBG, and no evidence of molecular aggregation was found by gel filtration. Although the electrophoretic mobility, isoelectric profile and immunochemical identity of CBGv appeared to be similar to normal CBG, it focussed as two distinct bands (pI 5·48 and pI 5·53) after desialylation with neuraminidase, unlike normal CBG which focusses only at pI 5·48. Investigation of the steroid binding characteristics of CBGv revealed a reduced association-rate constant (K a = 1·05 × 109 1/mol) and dissociation half-time (12·5 min) when compared with normal CBG (K a = 1·39 × 109l/mol and 25 min at 0 °C) but an apparently normal steroid binding specificity. Although the physiological significance of this variant is not known, the cortisol concentration in the variant serum was within the normal range of women during late pregnancy. No other CBG variants were identified among other normal controls (n = 66) or nine patients with Cushing's syndrome. It is suggested that comparisons between cortisol binding capacity and RIA will reveal other variants of CBG, and lead to greater understanding of their physiological significance.
J. Endocr. (1985) 104, 269–277
Search for other papers by KAREN R. CLARKE in
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SUMMARY
Rats were fed on a low protein (LP) and a glucose—filter paper (GFP) diet; they were then infected with 1000 larvae of the nematode worm Nippostrongylus brasiliensis (Travassos, 1914) and killed 5 or 10 days later.
The adrenals of male and female rats on the GFP diet for 21 days showed atrophy and so did those of female rats on the LP diet for 42 or 56 days. The adrenals of male rats on the LP diet for 21 days were hypertrophic.
Referred to body weight, the adrenal weights of male rats on both diets were higher than those of the controls, the weights of the adrenals of female rats on the deficient diets were lower.
Adrenal weight and adrenal weight as a percentage of body weight were shown to bear no relationship to corticosteroid production in vitro, since the capacity for corticosteroid synthesis in vitro was increased in rats on the GFP diet only.
Significantly more parasites were found in the intestine after 5, but not after 10 days on both deficient diets suggesting that the deficient diets increased the susceptibility of the rats on initial contact with the parasite and before the development of acquired resistance. Later more parasites were lost by the rats on the deficient diets than from controls. These findings were not related to changes in the rate of corticosteroid synthesis.
The effects of stress, and the administration of cortisone or corticotrophin on host—parasite relationships is discussed in relation to the results of the present experiments. It is concluded that though these factors can increase susceptibility and lower acquired resistance, the effect on susceptibility can also be produced independently by severe dietary deficiency.
Search for other papers by R. W. ASH in
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SUMMARY
Steroid hormone concentrations in plasma have been measured in blood samples taken from conscious sows with ear vein catheters. In late pregnancy, the plasma progesterone concentration ranged from 6 to 12 ng/ml and it decreased in all animals before the onset of parturition. Total unconjugated oestrogens increased to high values of up to about 3 ng/ml in late pregnancy and then declined after the onset of parturition. Oestrone was the predominant unconjugated oestrogen measured. Plasma corticosteroid (mainly cortisol) concentration was about 33 ng/ml and showed no consistent change at the time of parturition.
During lactational anoestrum the plasma concentration of progesterone and total unconjugated oestrogens was very low, while that of corticosteroids was 21 ng/ml. When the piglets were weaned at 26–31 days, sows came into oestrus 4–12 days later, and this was preceded, or accompanied by, an increase in plasma oestrogens. In the luteal phase, plasma progesterone concentrations rose to 20–35 ng/ml. A sow whose piglets were removed at birth, showed signs of oestrus (vulval enlargement and a lordosis response), but a lack of receptivity to the boar associated with no detectable changes in the plasma oestrogen concentration; however, ovulation probably occurred since plasma progesterone values increased in a manner comparable to that found after the formation of normal corpora lutea in other sows. After a second non-receptive cycle, the sow was mated and became pregnant at the third post-weaning oestrus.
At parturition the concentration of progesterone and total unconjugated oestrogens was greater in placental venous plasma than in maternal jugular plasma, which indicates placental synthesis of these hormones. A greater concentration of plasma corticosteroids in foetal blood than in placental venous or maternal jugular plasma suggests foetal synthesis in late pregnancy.
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ABSTRACT
It is possible that some of the effects of sodium pentobarbitone on the hypothalamo-pituitary-adrenal axis in the intact animal may be attributable to direct actions on the adrenal cortex. The effects of the barbiturate on steroid production by rat adrenal preparations in vitro have therefore been examined. In zona glomerulosa cells, pentobarbitone inhibited basal steroid production in a dose-related fashion. For aldosterone and corticosterone, the doses required for 50% inhibition of production (IC50) were 1·2 mmol pentobarbitone/l and 3·7 mmol/l respectively. Steroidogenesis was inhibited at lower levels of pentobarbitone in the presence of 1 nmol ACTH/l (IC50 = 0·5 mmol pentobarbitone/l for aldosterone and 2·2 mmol/l for corticosterone). In zona fasciculata/reticularis cells, production of corticosterone was similarly reduced with an IC50 of 2·8 mmol pentobarbitone/l for basal production and 1·3 mmol/l for ACTH-stimulated production. The dose-related increases in corticosterone production produced by ACTH (0·1–1000 pmol/l) or dibutyryl cyclic AMP (0·1–1·0 mmol/l) were also eliminated in the presence of 2 mmol pentobarbitone/l. The effects of pentobarbitone (1–4 mmol/l) on the production of pregnenolone and deoxycorticosterone (DOC) were also studied. In zona fasciculata/reticularis cells, the responses of both pregnenolone and DOC were bell-shaped with increases at 1 mmol pentobarbitone/l, which fell back to control levels at 4 mmol pentobarbitone/l. Stimulation of DOC, accompanied by decreases in aldosterone and corticosterone production, was also seen in zona glomerulosa cells at 1 mmol pentobarbitone/l.
The effect of 1 mmol pentobarbitone/l on the conversion of 22(R)-hydroxycholesterol (5-cholestene-3β,22(R)-diol), pregnenolone, progesterone and DOC to corticosterone and aldosterone by zona glomerulosa preparations was studied. There was a comparable reduction in the conversion of these precursors (2 μmol/l) to aldosterone with yields decreased to 20–30% of those found in the absence of pentobarbitone. The dose required for 50% reduction of the conversion of progesterone (2 μmol/l) to aldosterone was 0·55 mmol pentobarbitone/l and for corticosterone the dose was 1·75 mmol pentobarbitone/l.
The results obtained show that pentobarbitone is an effective inhibitor of corticosteroid biosynthesis in rat adrenal cells, and suggest that its effects are brought about by inhibition of cytochrome P450-mediated hydroxylations.
Journal of Endocrinology (1993) 136, 75–83
Department of Animal Physiology, Cell Biology and Immunology Group, Department of Biochemistry, Radboud University, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands
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Department of Animal Physiology, Cell Biology and Immunology Group, Department of Biochemistry, Radboud University, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands
Department of Animal Physiology, Cell Biology and Immunology Group, Department of Biochemistry, Radboud University, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands
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Department of Animal Physiology, Cell Biology and Immunology Group, Department of Biochemistry, Radboud University, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands
Department of Animal Physiology, Cell Biology and Immunology Group, Department of Biochemistry, Radboud University, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands
Search for other papers by Karen M Leon-Koosterziel in
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Department of Animal Physiology, Cell Biology and Immunology Group, Department of Biochemistry, Radboud University, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands
Department of Animal Physiology, Cell Biology and Immunology Group, Department of Biochemistry, Radboud University, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands
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endocrinology in fishes: i) cortisol, the main corticosteroid exerts receptor-defined gluco- or mineralocorticoid actions and thus the regulation of water and mineral balance in fishes is not necessarily controlled by a mineralocorticoid and ii) the poorly
Search for other papers by CARMEN RIVAS in
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Search for other papers by SARA BORRELL in
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SUMMARY
The concentration of adrenaline, noradrenaline and corticosteroids in the adrenal glands of intact cats was studied after administration of corticotrophin (ACTH) or dexamethasone. The animals were treated with ACTH for 3, 7 or 14 consecutive days and killed 3 h (group A) or 24 h (group B) after the last injection. In group A the levels of corticosteroids were significantly increased. Significant decreases were found in group B. A significant decrease in noradrenaline concentration was found in all experiments after administration of both ACTH and dexamethasone. No significant change in the adrenaline level was observed after only 3 days of ACTH or dexamethasone administration, but significant decreases were obtained in both groups after injection of ACTH for 7 to 14 days. These findings suggest that the decrease in adrenal adrenaline may be secondary to the significant and greater decrease in adrenal noradrenaline and that in the intact cat the glucocorticoid levels, although regulating the activity of the adrenal enzyme for methylation of noradrenaline, may not be the only factor involved in the control of adrenaline production by the adrenal gland.
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SUMMARY
The assays of testosterone and corticosteroids in plasma from adult male rhesus monkeys using competitive protein-binding and radioimmunoassay techniques are described. The radioimmunoassay for testosterone was conducted without chromatography and, therefore, additionally estimated 17β-hydroxy-5α-androstan-3-one (dihydrotestosterone). Levels of testosterone in the peripheral plasma of 14 intact male rhesus monkeys showed marked fluctuations over a period of 24 h. Concentrations of testosterone at 22.00 h (1776 ± 814 ( ± s.d.) ng/100 ml) were approximately double those at 08.00 h (858 ± 407 ng/100 ml), 12.00 h (898 ± 316 ng/100 ml) and 16.00 h (784 ± 530 ng/100 ml). Castration resulted in low plasma testosterone levels (85 ± 29 ng/100 ml), and the increases at 22.00 h were no longer observed. In intact males, the 'basal' plasma corticosteroidlevel(08.00 h) was 22·4 ± 6·0 μg/100 ml. Administration of synthetic corticotrophin raised plasma corticosteroid levels without changing plasma testosterone concentration. Because plasma testosterone levels were not related to changes in adrenocortical activity, the noctural rises appear to be due to changes in testicular secretion.
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SUMMARY
1. The characteristic response of the autotransplanted adrenal gland of the sheep to sodium depletion was an increase in aldosterone secretion rate, which reached the minimum detectable level of 1 μg/hr 6–12 hr after the Na balance became negative, when the Na deficit was approx. 200 m-equiv.
2. After its initial detection, aldosterone secretion altered in an irregular manner to maximum secretion rates of 5–9 μg/hr.
3. The initial detection of aldosterone secretion was not accompanied by any consistent changes in cortisol and corticosterone secretion.
4. Changes in cortisol and corticosterone secretion rates were usually in the same direction and of similar relative magnitude, and did not show any consistent correlation with the aldosterone secretion rates. The rates of cortisol and corticosterone secretion were extremely variable, but there was inconclusive evidence that there may have been a natural periodic variation of secretion rate, characteristic for individual sheep, which was modified by the experimental procedure.
5. The relationship between adrenal corticosteroid secretion and changes in blood plasma and urine electrolytes as well as haematocrit, plasma protein concentration and adrenal blood flow was examined.
6. Attention is drawn to the possible complexity of the relationship between adrenal corticosteroid secretion and the salivary Na/K ratio.
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Aldosterone, at a concentration of 10−8mol/l, increases the short-circuit current (scc, a measure of active sodium transport) across the skin of the frog (Rana pipiens). The other natural amphibian corticosteroid hormone, corticosterone, is about 100 times less potent. The structure–activity relationships of a number of corticosteroids were studied with respect to this response. An 11β-hydroxyl group was essential, whereas unsaturation at the C-1 to C-2 positions abolished activity. A 17-hydroxyl group did not enhance the response. Fluorination at the 9α-position increased the affinity of the steroid for the receptor. Synthetic corticosteroids which have a high ratio of glucocorticoid : mineralocorticoid action can increase the scc and one of these, dexamethasone, was even more potent than aldosterone. A methyl group at C-16 appeared to be an important constituent for this response but it had to be in the α-position. The effects of both aldosterone and dexamethasone were inhibited by spironolactone. The results are discussed in relation to the nature of the response and to corticosteroid receptors in the skin of amphibians.
