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At least 559 records · Page 31Linked to original sources
PubMed1982

Effects of tamoxifen on the serum levels of oestrogens and adrenocortical steroids in postmenopausal breast cancer patients.

Peripheral serum levels of cortisol, dehydroepiandrosterone (DHA), dehydroepiandrosterone sulphate (DHA-S), oestradiol-17 beta and total oestrone were measured in 17 postmenopausal breast cancer patients and on age-matched healthy controls. In the breast cancer patients analyses were performed before and after 1, 2, 4, 8 and 12 weeks of treatment with tamoxifen. Basal DHA levels were significantly higher in breast cancer patients than in controls; otherwise no significant differences were noted. Treatment with tamoxifen resulted in significantly elevated levels of cortisol throughout the period of treatment; this effect was probably solely due to an increase in transcortin levels. A transient but significant elevation in total oestrone, probably related to liver function, was observed after one week of treatment. No significant effects of tamoxifen were noted on serum DHA, DHA-S or oestradiol-17 beta. The results indicate that tamoxifen does not affect the adrenocortical steroid biosynthesis in postmenopausal women. The oestrogenic effects of tamoxifen upon FSH, prolactin and the oestrogen induced Pregnancy Zone Protein (PZP) in postmenopausal women, described in a previous communication from this group, are probably not due to any increase in the serum oestrogens since this increase is transient and hardly impressive. The weak oestrogenic effect of the tamoxifen-receptor complex itself may thus be sufficient to produce net oestrogenic effects in subjects with low endogenous oestrogens such as postmenopausal women.

Adrenal Cortex Hormones↗
PubMed1981

Glucocorticoid binding and control ACTH secretion.

This report attempts to summarize the present state of knowledge concerning interaction of glucocorticoids with brain and pituitary receptors, in relation to induction of specific biological effects. It examines the properties of the receptors, emphasizing the fact that transcortin-like binding molecules are present on the cell membrane in the pituitary gland. Also, it considers the functional aspects of the mechanism of action of steroids, including control, occupancy and heterogeneity of binding sites, as well as correlation with regulation of ACTH release.

Adrenocorticotropic Hormone↗
PubMed1982

Responses of salivary cortisol levels to stress-situations.

A procedure is described for determining salivary cortisol levels by a competitive protein-binding assay using horse transcortin. The collection of saliva was performed by means of filter paper-strips. Filter paper samples are more than 5 days stable after air-drying. In this form, the samples could be stored without refrigerator or deep-freezer and, if necessary, sent by post to the laboratory without any special precaution. Stressful situation of either painful or anxious origin were associated with an adequate increase of salivary cortisol levels. The increases were 157 to 230% of the initial or normal values dependent on the kind of stress. The mean values in 4 cases of Cushing's syndrome were 380% and 1 hour after 25 I.U. ACTH 690% higher than those in normal persons. In normal persons, a well-defined circadian rhythm has been observed.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

[Free and protein-bound corticosterone levels of the plasma of white rats under hypoxia and after administration of adrenocorticotropic hormone].

It has been demonstrated that the plasma ratio of free and protein-bound corticosterone depends on the hypoxic degree. After two-hour hypoxia at an altitude of 10,000 m the trained and untrained animals exhibit a similar content of the free hormone (21%), with the content of total corticosterone being significantly lower in the trained rats. A study of variations in the content of free corticosterone in rats exposed to hypoxia for 20, 45 and 120 min and ACTH administration during the same time intervals has shown that the binding capacity of transcortine changes 45 min after the beginning of hypoxia.

11-Hydroxycorticosteroids↗
PubMed1983

[Serum cortisol fractions in breast cancer].

Serum cortisol fractions were determined by isocolloidosmolar equilibrium dialysis in 93 women with breast cancer and 29 normal women. In breast cancer patients, the percentage of protein-unbound cortisol was increased at any concentration of total serum cortisol; this was accompanied by a relative decrease in the percentage of transcortin-bound cortisol. A significant increase in the unbound fraction is indicative of accelerated physiological activity of cortisol in breast cancer patients. In the breast cancer cases, there was a high incidence of obesity (61%) and impaired glucose tolerance (85%). In obese and/or diabetic patients, more remarkable increases of unbound cortisol were observed. We suggest that obesity and impaired glucose tolerance may increase the risk for breast cancer, and that the characteristic increase in the unbound cortisol fraction in women with breast cancer may reflect such risk factors.

Adult↗
PubMed1984

[Clinical course and pathophysiology of hyperthermia].

In 221 hyperthermic baths with 138 healthy volunteers thermoregulatory, circulatory, respiratory, renal, hematological, immunological, and endocrinological function values and sudomotoric activity have been determined. The endocrinological investigations demonstrate an increased glucocorticoidal activity (eosinopenia, T-lymphocytopenia) while plasmatic cortisole concentrations are slightly decreased. This discrepancy may be explained by an increased dissociation of biologically active cortisole and transcortin and by a more rapid activation of the steroid-receptor complex within the endocrine target cell. During a series of ten hyperthermic baths on ten consecutive days mineralocorticoidal activity during hyperthermia is increased (sudomotor activity, excretion of urine and sodium); urinary excretion of aldosterone does not change. These results indicate an increased sensitivity of the mineralocorticoidal target cell after adaptation to heat. The hypothesis can be confirmed by experiments with aldosterone i.v.

Aldosterone↗
PubMed1984

Beta-lapachone, a specific competitive inhibitor of ligand binding to the glucocorticoid receptor.

Beta-Lapachone, a derivative of 1,2-naphthoquinone, inhibits the specific binding of [6,7-3H]triamcinolone acetonide (TA) to unbound hepatic and thymic glucocorticoid receptors in a dose-dependent manner with 50% of the maximal inhibition in thymus cytosol achieved at a final concentration of 5-10 microM. Preincubation of cytosol with 10 mM Na2MoO4, which stabilizes unbound receptors, potentiates the subsequent beta-lapachone-mediated inhibitory activity, while preincubation with 1 or 10 mM dithiothreitol blocks the subsequent inhibition of [6,7-3H]TA binding. A double reciprocal plot indicates that beta-lapachone is a competitive inhibitor of [6,7-3H]TA binding with an apparent Ki of approximately 6 microM. The ability of beta-lapachone to displace prebound [6,7-3H]TA and the ability of elevated concentrations of [6,7-3H]TA to reverse the beta-lapachone-mediated inhibition are totally consistent with this kinetic interpretation. The ability of beta-lapachone to interact directly with the ligand-binding site is confirmed by the fact that this compound can block the binding of [6,7-3H]TA to highly purified unactivated hepatic glucocorticoid receptors. Although beta-lapachone may interact specifically with receptor sulfhydryl groups, this compound is not a general oxidizing agent which inactivates the essential free sulfhydryl groups at the glucocorticoid-binding site. Beta-Lapachone does not affect activation of [6,7-3H]TA-receptor complexes nor does it itself act like a glucocorticoid and facilitate receptor activation (transformation). Interestingly, this compound does not affect the ligand-binding sites of estrogen, progesterone, androgen, or mineralocorticoid receptors or serum transcortin. Thus, beta-lapachone can be utilized as a specific probe for the ligand-binding site of the glucocorticoid receptor.

Adrenalectomy↗
PubMed1984

Parotid saliva cortisol in normal subjects: increase during pregnancy.

Cortisol concentration was measured by radioimmunoassay in parotid saliva: values for normal subjects averaged 15 nM at 8:00 and 4 nM at 18:00. Parotid saliva cortisol was shown to react promptly and in a clearcut fashion to factors leading to rise and fall in cortisol secretion. Cortisol levels in parotid saliva were uninfluenced in young women taken estrogen-containing drugs for contraceptive purposes; on the other hand, they increased significantly during the third trimester of pregnancy. This increase corresponds to the reported increase in ultrafilterable cortisol, itself being presumably the result of the hypersection of progesterone characterizing this physiological condition since progesterone competes with cortisol not only at the level of transcortin but also at that of cytoplasmic glucocorticoid receptors.

Adult↗
PubMed1981

The effect of a very-low-calorie diet with and without chronic exercise on thyroid and sex hormones, plasma proteins, oxygen uptake, insulin and c peptide concentrations in obese women.

In 18 obese women a very-low-calorie diet (VLCD) has been combined with exercise (three times a week = 1650 kcal/week; 6.9 MJ) and compared with the effects of diet alone. The adherence and tolerance of the diet was quite good. Oxygen uptake decreased significantly only in the exercising group. Sex hormones binding globulin increased while prealbumin and retinol binding protein decreased in both groups. Changes in T4, T3, rT3, TSH, TBG and insulin secretion appeared to be equal in both groups. No significant differences between the two groups have been found with respect to body weight, body fat and lean body mass loss. Glucose tolerance deteriorated in the diet only group but remained unchanged in the group combining diet and exercise. Insulin production after oral glucose load did not change in either of the two groups. A more pronounced decrease in c peptide concentration has been observed in exercising groups. Sex hormones binding globulin and testosterone concentration increased in both groups. No changes have been detected in the concentration of transcortin. It is concluded that during a short period of VLCD exercise did not produce a higher body weight loss nor a protective effect on lean body mass.

Blood Proteins↗
PubMed1982

[Accumulation by preparations of rat heart sarcolemma of protein-bound forms of glucocorticoids].

The accumulation of free and protein-bound forms of [3H]corticosterone and [3H]dexamethasone by preparations of heart sarcolemma from adult male Wistar rats was studied. At physiological concentrations of glucocorticoids the sarcolemma preparations showed a considerably greater accumulation of the cytosol-bound form of glucocorticoids as compared to the free form. On the contrary, the formation of [3H]corticosterone-transcortine complex decreased the steroid uptake by the membranes under these conditions. The [3H]steroid-albumin complexes obtained by incubation of very high concentrations of [3H]glucocorticoids with pure albumin were retained by the membranes better than the free form of the hormones. The differences in the accumulation by membranes of steroid--cytosol and steroid--albumin complexes during temperature rise from 0 degrees to 20 degrees C were found. The increase in the uptake of steroid--cytosol complexes was evidently caused by thermal "activation" of the complexes, while the temperature influence on the steroid--albumin complexes accumulation by sarcolemma preparations was directly due to the uptake process. An addition of molybdate (blocker of steroid--receptor complexes activation) at a concentration of 100 mM completely eliminated the thermal effect on the steroid--cytosol complexes accumulation.

Albumins↗
PubMed1981

Level of glucocorticoid receptors in male rat liver under stress.

The binding of dexamethasone and corticosterone by specific glucocorticoid cytoplasmic liver receptors has been studied in intact, adrenalectomized and stressed male Wistar rats. The dissociation constants measured for receptor-hormone complexes were 7.2 x 10(-9) M for dexamethasone and 5.0 x 10(-9) M for corticosterone. Under 48 hour immobilisation stress, the number of binding sites on a dexamethasone-binding receptor was found to diminish from 2.9 x 10(-13) mol/mg protein (for intact rats) to 0.8 x 10(-13) mol/mg protein (for stressed rats). The amount of binding sites on a transcortin-like receptor decreased from 10 x 10(-14) mol/mg protein (in the intact rats) to 2.8 x 10(-14) mol/mg protein (in the stressed ones). Thus above data indicated certain reduction in binding site number for dexamethasone and corticosterone on the specific cytoplasmic receptors of rat liver under immobilisation stress.

Adrenalectomy↗
PubMedDate not supplied

[Hormonal function of the adrenal cortex in "medical castration" induced by prolonged infusion of luliberin agonists].

Time course of the major corticosteroid hormones and the precursors in the biosynthesis chain was studied, as was the type of corticosteroid complex formation with transcortin in the peripheral blood plasma in male papua hamadryas exposed to a 4-16 week infusions of LH releasing factor agonists (buserelin, Hoechst A. G., Germany, and surfagon, Cardiology Research Center of the Russian Academy of Medical Sciences) with the use of osmotic mini-pumps (Alza Corp., Palo Alto, USA). Suppression of the gonadal function resultant from prolonged infusion of LH releasing factor agonists was not associated with essential shifts in the adrenal steroidogenesis and in the specific corticosteroid transport. Such exposure induced a somewhat more marked activation of glucocorticoid and adrenal androgen secretion in response to acute stressor exposure (a single injection of insulin in a dose of 0.2 U/kg b. m.). One should bear in mind this fact when prescribing therapy with LH releasing factor agonists to patients with prostatic carcinoma, for the adrenal androgens are transformed into active androgens in the prostatic tissue.

Adrenal Cortex Hormones↗
PubMed1976

[Variation in total and unbound plasma cortisol levels throughout labor in normal and anencephalic pregnancies].

Total and unbound plasma Cortisol levels have been evaluated throughout labour in women delivering normal and anencephalitic infants. The sharp increase in total Cortisol usually observed in maternal plasma during labour does not occur in women bearing an anencephalitic foetus. This Cortisol binding capacity of Transcortin being the same, both in the normal and the pathological groups, it is shown that in anencephaly, unconjugated Cortisol levels are also lowered. The maternal contribution to the plasma Cortisol increase being identical in all cases, our data suggest that in anencephaly, a lack of foetal contribution might be responsible for the low Cortisol levels observed throughout labour.

Anencephaly↗
PubMed1993

Consideration of sheep as a minor species: comparison of drug metabolism and disposition with other domestic ruminants.

The processes which determine bioequivalence of a given drug among species are many, and include absorption from a site of administration, renal, biliary and intestinal elimination, sequestration (in particular, binding to proteins or other macromolecules), distribution and redistribution, biotransformation, and receptor population density and uniqueness. The present review is limited to physiologic and pharmacologic parameters which affect drug distribution, elimination, and metabolism, primarily because these are areas where sufficient data is available to make comparisons between sheep and other ruminants. The literature suggest a high degree of similarity among domestic ruminants in the distribution and elimination of drugs that are not metabolized but eliminated by passive processes such as renal glomerular filtration. Although the data are not as uniform as when conducted under rigorous control in the same laboratory setting, it is possible to predict very similar pharmacokinetic profiles for many of the antimicrobials between cattle, sheep and goats. Metabolic scaling of kinetic parameters could be predicted in comparative studies conducted under well-controlled conditions, in which case the greatest similarities would occur among the small ruminants with values being somewhat dissimilar between sheep or goats and cattle. Plasma protein binding of drugs appears to be very similar among the ruminants, and its influence on drug distribution and elimination does not appear to vary appreciably between cattle and sheep. There is, however, very little definitive data which describes binding parameters, and there is very little data of any kind on binding to caprine albumin other plasma proteins of the goat. Sheep apparently differ from cattle, however, in transcortin concentrations, and this could affect the distribution and elimination of prednisolone or any other synthetic steroid which exhibits high affinity binding to this transport protein. Among the drug substances for which comparative information is available, there is very little to suggest qualitative differences in routes of metabolism among ruminants. There appears to be a remarkable degree of similarity in both major and minor pathways of drug metabolism among these species, and in fact, no documentable differences of a qualitative nature have been found. It should be noted, however, that documentable differences would only be established in a direct comparison of species conducted in the same laboratory under carefully controlled conditions. Such conditions would necessarily include assurance of no recent exposure to enzyme inducing agents or inhibitors or to agents which could deplete endogenous substances necessary to the enzymatic process.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1977

Detection of genetic variation with radioactive ligands. I. Electrophoretic screening of plasma proteins with a selected panel of compounds.

To detect new genetic variation in human plasma proteins, a panel of 63 radioactive substances were screened as potential radioligands using polyacrylamide gel electrophoresis (PAGE) and autoradiography. Vitamins, hormones, drugs, amino acids, purines, pyrimidines, sugars and lipids labeled with 14C or other radionuclides were among those substances tested. A majority bound to albumin and a smaller fraction to prealbumins and lipoproteins. Several vitamins and hormones bound to specific alpha and beta globulins. (1) Electrophoretic polymorphisms of vitamin D-binding protein (group-specific component), a vitamin B12-binding protein (transcobalamin II), and thyroxine-binding alpha-globulin are described elsewhere. (2) Testosterone-binding beta-globulin (TeBG) showed an electrophoretic polymorphism in Caucasians and a possible deficiency allele. (3) Transcortin showed an electrophoretic doublet in all persons tested but no electrophoretic variation. (4) A protein binding derivative of norepinephrine or epinephrine was identified as transferrin. (5) A nonpolymorphic protein running cathodal to albumin and binding a derivative of riboflavin was tentatively identified as a fraction of albumin with mobility altered as a result of interaction with the ligand.

Adult↗
PubMed1993

Influence of gestodene and desogestrel as components of low-dose oral contraceptives on the pharmacokinetics of ethinyl estradiol (EE2), on serum CBG and on urinary cortisol and 6 beta-hydroxycortisol.

A randomized controlled clinical trial was undertaken over a 6-month treatment period with two low-dose combined oral contraceptives (OC) to investigate whether the metabolism and elimination of ethinyl estradiol (EE2) is differently influenced by the two progestational components gestodene (G) and desogestrel (D), an issue which has been very controversial recently. The two formulations contained 30 micrograms EE2 each, together with either 75 micrograms G or 150 micrograms D. Of the 40 young women recruited for each formulation, 31 of each group were available for statistical evaluation. The pharmacokinetics of serum EE2 were studied on day 1, 10 and 21 of cycle 1, 3 and 6. There were no significant differences between the two groups in any cycle with respect to parameters measured. This was true for the distinct intracyclical rise in the mean EE2 serum levels from day 1 to day 10 and the smaller further increase between day 10 and day 21, with no change in this respect between the cycles studied. Respective changes were seen with regard to the area under the EE2 serum concentration curve up to 4 and 24 hours (AUC0-4 and AUC0-24), cmax and tmax of serum EE2. The estrogen-dependent corticoid-binding globulin (CBG) increased similarly in the two groups intracyclically and slightly also intercyclically at all times tested. Except for the first treatment cycle, urinary excretion of cortisol and 6 beta-hydroxycortisol displayed a tendency to lower values intracyclically as well as intercyclically, again with no differences between the two groups. Also, the 6 beta-hydroxycortisol-to-cortisol ratio was not different between the groups, showing a slight tendency to rise from about 4 at the beginning of the medication to around 5.5 at the end of the 6th treatment cycle in both groups. It is concluded that G and D as components of low-dose OCs exert comparable effects on the metabolism and elimination of EE2.

Adult↗