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PubMed2001

A preliminary study of circadian serum cortisol concentrations in response to a 72-hour fast in rheumatoid arthritis patients not previously treated with corticosteroids.

The aim of the study was to investigate the effects a 72-h fast upon serum total and free cortisol concentrations in RA patients not previously treated with glucocorticoids. Total serum cortisol and transcortin concentrations were measured in four RA patients with active disease at 4-h intervals during two 24-h periods (1200 h-1200 h), the first while eating a normal diet (fed state) and the second during the last 24 h of a 72-h water fast. Free cortisol concentrations were calculated from the total cortisol and transcortin values. The 3-day fast increased overall 24-h free and total cortisol concentrations by 50% and 35%, respectively. This was due largely to a marked increase in nocturnal serum cortisol concentrations during fasting, particularly at 0400 h, when mean total and free cortisol levels were increased by 170% and 260% compared to the fed state. Between 2000 and 0800 h overall total- and free cortisol concentrations were increased by 72% and 99%, respectively. These results suggest that an increase in nocturnal concentrations of cortisol occurs in response to fasting in RA patients not previously treated with glucocorticoids. These increases may mediate the beneficial clinical response previously found in studies of longer fasting periods in RA patients.

Adult↗

PubMed1975

Estrogen and the metabolism of progesterone in vivo.

The effect of estrogen administration on the metabolism of progesterone was studied in ovariectomized, hysterectomized women. Estrogen was withheld from each subject for at least 4 weeks, then 200 mug of ethinyl estradiol were administered orally each day for 3 weeks and then no estrogen was given for 3 weeks. The subjects were studied before estrogen was started, on the third day of estrogen, after 3 weeks of daily estrogen and after the estrogen was withdrawn for 3 weeks. In 5 women plasma transcortin concentrations, measured by equilibrium dialysis, were 0.82 plus or minus 0.06, 1.5 plus or minus 0.16, 2.1 plus or minus 0.13, and 0.90 plus or minus 0.09 (S. E.) muM before starting estrogen (control), on the third day of estrogen treatment, after 3 weeks of estrogen, and after having stopped estrogen for 3 weeks, respectively. Corresponding values for the metabolic clearance rates (MCR) of cortisol (by the continuous infusion method) were 306 plus or minus 33, 172 plus or minus 18, 136 plus or minus 14, and 258 plus or minus 23 (S. E.) L. per day. Although estrogen administration caused a significant elevation of the plasma transcortin concentrations and a significant decrease in the MCR of cortisol, it had no significant effect on the MCR of progesterone or of cortisone. The estrogen administration did cause a decrease in the peripheral conversion of progesterone to 20alpha-hydroxy-pregn-4-en-3-one (20alpha-OHP) and of cortisol to cortisone but an increase in the conversion of 20alpha-OHP to progesterone and of cortisone to cortisol.

Adult↗

PubMed1978

Ethinyl estradiol administration and plasma steroid concentrations in ovariectomized women.

The effect of ethinyl estradiol treatment on the plasma levels of cortisol, corticosterone, deoxycorticosterone, progesterone, testosterone, dehydroepiandrosterone sulfate, delta4-androstenedione, and estrone was studied in eight women. All the subjects had undergone ovariectomy and hysterectomy at least one year prior to this study. The systemic concentration of cortisol and the binding of cortisol were significantly increased, paralleling the increased transcortin concentration due to ethinyl estradiol treatment. Corticosterone concentration was also significantly increased after three days of estrogen administration and this level continued to be higher than normal as long as patients were treated with estrogens, but there was no change in the plasma concentration of deoxycorticosterone. The plasma levels of progesterone testosterone, dehydroepiandrosterone sulfate, delat4-androstenedione and estrone or the ratio of estrone to delta4-androstenedione did not change with ethinyl estradiol treatment. These observations suggest that the administered estrogen increased the transcortin concentration and had only a limited effect on adrenocortical steroidogenesis.

Adult↗

PubMed1982

Two oral contraceptives, efficacy, serum proteins, and lipid metabolism. A comparative multicentre study on a triphasic and a fixed dose combination.

A triphasic, combined oral contraceptive containing 30 - 40 - 30 micrograms ethinyloestradiol (EE), and 50 - 75 - 125 micrograms levonorgestrel was compared with a fixed dose combination containing 30 micrograms EE and 150 micrograms desogestrel in a randomized multicentre trial in 193/199 women and 1 063/1 073 cycles, respectively. The duration of the trial was six months. Eleven centres in Denmark, Sweden, and Norway participated. Contraceptive reliability, bleeding control and side effects were evaluated. Influence on serum sex hormone binding globulin (SHBG) and transcortin was assayed as well as lipid metabolism. Three pregnancies occurred in the group using the triphasic regimen but none in the fixed dose regimen. Two of the three pregnancies were considered drug failures and the third a possible interaction. Possible reasons for the triphasic contraceptive failure are discussed with special reference to a British report on eight pregnancies. Bleeding control appeared to be equally good for the two preparations. However, the number of cycles with spotting, breakthrough bleeding and missed withdrawal bleeding were above the levels reported earlier on the triphasic regimen. About 80 per cent of the women completed the planned six months on either combination. Side effects were generally mild and in accordance with earlier reports on low dose oral contraceptives. Metabolically the triphasic levonorgestrel combination increased SHBG 100 per cent versus 200 per cent for the fixed desogestrel combination. Transcortin rose about 98 and 110 per cent, respectively. Both preparations induced similar changes in the levels of lipids and lipoproteins with the exception of a significant increase in the arachidonic content of cholesterol during treatment with the desogestrel-containing preparation.

Adolescent↗

PubMed1982

Interrelations between binding affinity and metabolic clearance rate for the main corticosteroids in the rabbit.

In the rabbit, the metabolic clearance rate (MCR) was found to be higher for corticosterone than for cortisol. At the same time corticosterone, aldosterone and 11-dehydrocorticosterone showed similar MCR while cortisone ranged at intermediate levels between cortisol and corticosterone. The relative binding affinity of transcortin to the corticosteroids, as calculated by an in vitro technique, decreased progressively from cortisol, to cortisone, then to corticosterone, then 11-dehydrocorticosterone and, finally to aldosterone. The occurrence of antibodies in plasma, induced against aldosterone, corticosterone or even cortisone resulted in a marked decrease in the MCR of the corresponding steroid, to the level measured in controls for cortisol. We deduced that, in rabbits: (1) the MCR of a corticosteroid is clearly connected with its binding to a specific protein; (2) in spite of the relatively high binding affinity of transcortin for corticosterone as compared to other species it nevertheless appears unable to significantly protect the steroid against peripheral metabolism; (3) a very effective protection is however, induced, by raising a specific antibody with a high binding affinity for corticosterone.

Adrenal Cortex Hormones↗

PubMed1986

Steroid-carrier proteins in patients with multiple myeloma.

Patients with multiple myeloma have transcortin levels lower than normal. This is due in essence to a subgroup of patients producing IGG heavy chains with lambda light chains. Patients producing IGG with predominantly kappa light chains have almost normal transcortin levels. On the other hand, the binding activity of the steroid binding beta globulin (SB beta G) of the kappa type of multiple myeloma is significantly higher than the steroid binding of the lambda type of multiple myeloma. The serum levels of vitamin D binding protein (DBP) fall in the normal range.

HLA Antigens↗

PubMed1997

Features of the shuttle pair 11 beta-hydroxyprogesterone-11-ketoprogesterone.

11 beta-hydroxyprogesterone (HOP) and 11-ketoprogesterone (KP) are reversible components of a shuttle pair whose interconversion in rat liver is catalyzed by isoform-1 of 11 beta-hydroxysteroid dehydrogenase. Kidneys also produce this interconversion. The present study was carried out to investigate the shuttle pair and its components in the rat. As in corticosterone/11-dehydrocorticosterone, oxidation is more effective at an alkaline pH, while reduction prevails at a neutral pH. Moreover, both reactions are inhibited by the detergent 3-[(3-cholamido propyl)-dimethylammonio]-1-propane-sulphonate (CHAPS). However, at variance with the 11-ketosteroids cortisone (E) and 11-dehydrocorticosterone (A) thought to be "inactive," KP has slight direct Na(+)-retaining properties, and it, as well as HOP, induces glucocorticoids (11 beta-hydroxycorticoids) to retain sodium. 11-ketoprogesterone exhibits 17 times better affinity for native type 1 mineralocorticoid receptor than HOP and a 3-fold affinity for partially purified (transcortin free) mineralocorticoid receptor. However, KP, in contrast to HOP, binds only weakly to transcortin, not at all to glucocorticoid receptor, and requires reduction at C11 for tyrosine aminotransferase (TAT) induction.

11-beta-Hydroxysteroid Dehydrogenases↗

PubMed1978

[Electron paramagnetic resonance study of the interactions between steroid hormones and binding proteins].

Interaction of a spin labeled corticosteroid (desoxycorticosterone nitroxyde: DOC -NO) with three purified proteins (albumin, transcortin, progesterone binding protein: PBG) was studied by electron spin resonance (ESR) spectroscopy. DOC-NO was competitive with natural corticosteroids and therefore bound at the same site to specific binding proteins. ESR spectra in the presence of each of the proteins showed an immobilized (bound) form of the spin labeled steroid and allowed the calculation of the corresponding association constant (Ka) at equilibrium. The three binding proteins could be characterized by the ESR parameters of the DOC-NO bound form. The thermodynamic parameters (deltaH, deltaS) of the steroid-protein interactions were calculated from the ESR data obtained within a wide temperature range (3--40 degrees C). The ESR spectra width (2T) was used to evaluate the polarity of the spin label environment within the steroid binding site: a hydrophobic character was observed for transcortin whereas PBG exhibited a more hydrophilic steroid binding sits. The rotational correlation time of the three protein DOC-NO complexes at equilibrium were calculated from ESR data; the results were correlated with the protein molecular size and suggested a non spherical shape for the binding macromolecule in solution. Spin labelling of biologically active steroids thus provides a novel approach for the study of the interaction of these hormones with their binding protein. Providing a suitable spin label, the ESR parameters may allow the characterization of several types of binding sites of different biological significance for the same hormone, in biological fluids as well as in target tissues.

Alpha-Globulins↗

PubMed1980

Maturation of glucocorticosteroid activity in the foetal guinea-pig during the end of gestation.

Cortisol levels were very high in maternal and foetal plasma during the last days of pregnancy. The percentage of free cortisol was maximal in plasmas of the mother and the foetus on the last day before parturition; the increase in free cortisol levels resulted from the saturation of transcortin binding capacity and from a higher adrenal secretion rate at that time due to stress at the onset of labor. On the last day of pregnancy the foetal adrenals could cover the hormonal needs of the foetus, the foetal-maternal transfer of cortisol being similar to the maternal-foetal transfer. However, the low TCM at cortisol indicated that cortisol catabolism was still immature. The origin of foetal transcortin is still unknown.

Adrenal Glands↗

PubMed1988

Responses of serum androgenic-anabolic and catabolic hormones to prolonged strength training.

Endocrine and neuromuscular effects of prolonged strength training were investigated in 21 strength-trained male subjects during the course of a 24-week progressive strength training and during a subsequent detraining period of 12 weeks. Maximal isometric leg extensor force increased by 19% (P less than 0.001) during the first 20 weeks, followed by a plateau during the 4 latest weeks of training. During the course of the training period, no systematic change was found in serum testosterone concentrations, but there was a decreasing tendency in the concentrations of free testosterone (NS), 17-OH-progesterone (NS), androstenedione (P less than 0.05), dehydroepiandrosterone (P less than 0.05), cortisol (P less than 0.01), transcortin (CBG) (P less than 0.05), and in the cortisol/CBG ratio (P less than 0.05). The last 4 weeks of training were characterized by significant correlations between the individual changes in maximal isometric force and the changes in serum free testosterone concentrations (r = 0.60, P less than 0.01). The changes in the ratios of free testosterone to cortisol (r = 0.73, P less than 0.001), total testosterone to cortisol (r = 0.83, P less than 0.001), and 17-OH-progresterone to cortisol (r = 0.62, P less than 0.01) also correlated with the changes in maximal force. The findings suggest that the turnover of endogenous androgens may increase during progressively intensified training without a change in serum total testosterone concentration. Prolonged intensive strength training may also lead to changes in the concentrations of serum cortisol and transcortin. During the most stressful phases of training, the changes in serum androgen/cortisol ratios seem to be highly individual and may correlate with changes in muscular strength.

17-alpha-Hydroxyprogesterone↗

PubMed1988

Progestagen-dependent effect on some plasma proteins during oral contraception.

Seventeen healthy women received a combination of 0.030 mg of ethinyl estradiol and 0.150 mg of levonorgestrel or a combination of 0.030 mg of ethinyl estradiol and 0.150 mg of desogestrel for 2 years as oral contraception. Serum levels of sex hormone binding globulin, transcortin, ceruloplasmin, and pregnancy-associated protein were measured before contraception, during 3, 6, 12, 18, and 24 months of treatment, and 2 months after stopping the pill. Oral contraception with both preparations induced a similar, significant rise in both ceruloplasmin and pregnancy-associated protein. Sex hormone binding globulin levels rose significantly with the ethinyl estradiol-desogestrel, but not with the ethinyl estradiol-levonorgestrel combination. Transcortin increased with both preparations, more with the ethinyl estradiol-desogestrel combination.

Blood Proteins↗

PubMed1982

Release of protein bound progesterone in human serum by ioglycamide.

With the use of an aqueous two-phase system the influence of ioglycamide on the serum protein binding of progesterone was investigated. Ioglycamide was found to cause a decrease in the association constants for the binding of progesterone to both albumin and transcortin. The binding capacity for the progesterone binding to transcortin was also decreased. The decreased progesterone binding was discussed in terms of clinical relevance in connection with adverse reactions at cholegraphy with intravenous injection of ioglycamide.

Blood Proteins↗

PubMed1975

Non-chromatographic radiotransinassay for cortisol: application to human adult serum, umbilical cord serum, and amniotic fluid.

Rapid (1-2 hour) non-chromatographic radiotransinassay using horse transcortin can be used to measure cortisol in umbilical cord serum (after hexane-carbon tetrachloride prewash and methylene chloride extraction), in amniotic fluid (after methylene chloride extraction only), and in adult serum (after dilution and boiling without extraction). Since horse transcortin has high affinity (2.4 x 10(9) l/mol) for cortisol, only a few microlitres of sample is required. The assay appears to be highly specific for cortisol clinically except in congenital adrenal hyperplasia.

Amniotic Fluid↗

PubMed1975

Cortisol-binding protein in the cytosol of rat carrageenin granuloma.

Cortisol-binding protein was prepared and partially purified by (NH4)2SO4 fractionation and DEAE-cellulose column chromatography from 105,000 g supernatant fraction of cytoplasm in rat carrageenin granuloma, which is assumed to be one of the most appropriate experimental models of inflammation. The cortisol-binding protein in the inflammatous tissue, although similar to transcortine, was not transcortine itself. The binding protein was eluted at 0.12 M NaCl by DEAE-cellulose column chromatography with a shallow salt gradient. Sedimentation constant and dissociation constant of the binding protein were 4-5 S and 1.0 X 10(-9) M, respectively. Optimum pH for binding to cortisol was 8.0. Binding ability of the binding protein to cortisol was very sensitive to pronase E and trypsin but resistant to RNase. Specificity of the protein for binding other steroids revealed that 17beta-estradiol did not bind to the protein, while androstenedione and testosterone had one sixth as much affinity to the binding protein as that of cortisol. There was good a correlation between the amount of the binding protein in the inflammatory tissue and anti-inflammatory effect of cortisol. Namely, the maximum cortisol-binding ability was seen on a 5 day old granuloma which is the so called 'steroid sensitive stage'. Thereafter, the binding ability decreased with the increasing stage of granuloma.

Androstenedione↗

PubMed1978

Inverse effects of corticosterone and thyroxine on glucocorticoid binding sites in the anterior pituitary gland.

The aim of this study was to determine whether pituitary glucocorticoid binding sites are under hormonal control. It was shown that corticosterone and thyroxine exerted antagonistic effects on both the transcortin-like component and true receptor present in the hypophysis: thyroid hormones, in contrast to glucocorticoids which exhibited opposite influence, increased maximum binding without affecting significantly the apparent association constant. Thus, it seems that the concentration of glucocorticoid binding sites is regulated by the glucocorticoid ligands, as well as by a different hormone. Moreover, a striking parallelism was found between plasma transcortin and pituitary transcotin-like capacity, argueing in favour of a plasma origin for this pituitary binder.

Adrenalectomy↗

PubMed1979

Plasma clearance of cortisol as a function of plasma cortisol levels in normal and obese persons and in patients with uraemia or cirrhosis of the liver.

Plasma cortisol levels in 2 normal persons, 2 obese persons, 2 uraemic patients, and 2 patients with cirrhosis of the liver were raised in 4 steps by a combination of iv priming doses and continuous infusions of cortisol. Plasma cortisol levels and transcortin binding were measured as well as plasma clearance rates of labelled and unlabelled cortisol during each of the 5 experimental periods. Plasma cortisol levels increased less and plasma clearance rates of labelled and unlabelled cortisol increased more in obese persons than in normal persons; in patients with disturbed metabolism of cortisol (uraemia, cirrhosis of the liver) the reverse is true. Plasma clearance rates of free cortisol were calculated and differed from an estimated hepatic plasma flow of 0.7 1/min under certain conditions. Since free cortisol is metabolized faster than transcortin-bound cortisol, increasing plasma clearance rates of cortisol are probably due to increasing ratios free/bound cortisol when total plasma cortisol levels are raised. Low plasma clearance rates of cortisol in uraemia and cirrhosis of the liver are thought to be due to endproduct inhibition, respectively reduced liver cell mass.

Adult↗

PubMed1980

Role of testosterone in the sexual dimorphism of adrenal activity at puberty in the guinea-pig.

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.

Adrenal Glands↗

PubMed1981

Effects of oral contraceptive combinations containing levonorgestrel or desogestrel on serum proteins and androgen binding.

The effects of the oral contraceptive combinations 0.125 mg Org 2969 (desogestrel) (13-ethyl-11-methylene-18,19-dinor-17alpha-pregn-4-en-20-yn-17-ol) + 0.05 mg ethinyloestradiol (EE) and 0.125 mg levonorgestrel + 0.05 mg EE on serum sex-hormone-binding globulin (SHBG), ceruloplasmin, transcortin and ratio free testosterone over total testosterone (percentage free testosterone) and ratio free 5alpha-dihydrotestosterone over total 5alpha-dihydrotestosterone (percentage free 5alpha-dihydrotestosterone) were compared in healthy female volunteers. Treatment was randomly distributed over the volunteers; 11 women received Org 2969 + EE and 11 women received levonorgestrel + EE. These combinations induced similar increases in transcortin levels (115 and 140%) and ceruloplasmin levels (115 and 123%) after 3 months of treatment. However, the combination Org 2969 + EE induced a substantial increase (213%) in SHBG capacity after 3 months of treatment, whereas a smaller increase (80%) was observed with levonorgestrel + EE. A return to pretreatment values was observed 2 months after termination of treatment for all parameters. The difference in the effects of both preparations oh SHBG was statistically significant and can be best explained by a difference in the androgenicity of the progestogens. A good correlation was free testosterone and the reciprocal value of the percentage free 5 alpha-dihydrotestosterone. These results confirm that SHBG is the major regulator of the biologically active free androgen fraction in women before, during and after combined oral contraceptive treatment.

Adolescent↗