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PubMed1991

Serum corticosteroid-binding globulin (CBG) and hepatic CBG mRNA relationships during hamster pregnancy: contribution of decidualization.

We measured serum corticosteroid-binding globulin (CBG) and hepatic CBG mRNA from individual hamsters throughout pregnancy and during decidualization. Serum CBG levels were determined by 3H-cortisol binding assay, and hepatic CBG mRNA levels were measured by Northern blots and solution hybridization assays, using a 32P-labeled cRNA probe derived from a rat CBG cDNA. There was a positive relationship between hepatic CBG mRNA levels and serum CBG levels during pregnancy. Both parameters increased significantly from the time of mating (cycle Day 4) to pregnancy Day 4, showing that CBG synthesis and secretion increased prior to implantation (Day 4). After implantation, serum CBG and hepatic CBG mRNA rose further from pregnancy Day 4 to a peak on Day 14, then decreased before parturition on Day 16. The prepartum decline in hepatic CBG mRNA preceded the fall in serum CBG. Decidualization on pseudopregnancy Day 4 resulted in an increase in serum CBG and hepatic CBG mRNA. Hepatic CBG mRNA increased from Day 5 to Day 7, and serum CBG increased progressively from Day 5 through Day 9 after uterine decidualization in the hamster. The present results demonstrate that the pattern of serum CBG observed in the pregnant hamster follows closely that of hepatic CBG mRNA. A signal emanating from uterine decidual tissue appears to be important in the regulation of hepatic CBG synthesis and secretion during midpregnancy, but other unknown factors appear to be involved in controlling CBG during the early and late stages of pregnancy.

Animals↗
PubMed1997

Porcine fetal and maternal adrenocorticotropic hormone and corticosteroid concentrations during gestation and their relation to fetal size.

A study was conducted to characterize fetal plasma ACTH and corticosteroid concentrations during porcine gestation and to relate plasma corticosteroids to fetal size. Samples were taken in white crossbred pigs at 50, 75, and 100 days of gestation and in Chinese Meishan pigs at Day 75. Fetuses developed in either "crowded" or "roomy" uterine environments after maternal uterine ligation, and all fluid samples were obtained during surgery. Fetal arterial cortisol decreased by 30% between Days 50 and 75 and then increased by 101% between 75 and 100 days. Concomitantly, fetal arterial ACTH increased 4-fold between 50 and 75 days of gestation and 45% between 75 and 100 days. Fetal venous cortisol and ACTH (measured only on Days 75 and 100) concentrations were lower than arterial concentrations. Both amniotic and allantoic fluid cortisol concentrations paralleled those of arterial cortisol but were at least 4-fold less. The percentage of free cortisol on Days 75 and 100 was a constant 24%, whereas cortisol bound to corticosteroid-binding globulin was a constant 60% and albumin-bound cortisol was 16%. White crossbred fetal arterial cortisone concentrations were always lower than cortisol concentrations, did not differ between arterial and venous plasma, decreased 50% between 50 and 75 days, and did not change thereafter. Plasma cortisol concentrations in Chinese Meishan fetuses were 30% greater than in white crossbred fetuses of the same age, but plasma ACTH and cortisone did not differ between breeds. Analysis of covariance indicated a negative regression of fetal weight and fetal length on arterial cortisol in white crossbred fetuses only at Day 100, and at Day 75 in Meishan fetuses. Under the specific conditions of this experimental model, these data demonstrate prenatal developmental changes in plasma ACTH and corticosteroids, indicate breed differences in such development, and suggest that a negative relationship exists between endogenous cortisol concentrations and fetal size at specific gestational ages.

Adrenal Cortex Hormones↗
PubMed1998

Intrauterine cortisol, aldosterone, and corticosteroid binding globulin-like activity during early porcine pregnancy and the estrous cycle.

Studies were conducted to determine whether the corticosteroids cortisol and aldosterone, and corticosteroid-binding globulin (CBG) were present in the porcine early-embryonic environment. Cortisol was measured in uterine flushings from white crossbred gilts at Days 7, 10, 13, and 16 of the estrous cycle and pregnancy. Total content of cortisol increased (p < 0.01) between Days 13 and 16, and immunoreactive CBG (ir-CBG) increased (p < 0.01) between Days 10 and 13, in both cyclic and pregnant gilts. In a separate study with Chinese Meishan gilts, total cortisol and aldosterone content of uterine flushings increased (p < 0.02) between Days 10 and 15 of the estrous cycle and pregnancy. In another study with white crossbred gilts, CBG-like binding activity in uterine flushings was low at Day 10, then increased over 100-fold at Day 15 (p < 0.01). However, levels of CBG-like binding activity on Day 15 were 100-fold lower than those of ir-CBG measured in the previous study and could bind less than 4% of the uterine luminal cortisol. Differences between ir-CBG and CBG binding might be due to the ability of the CBG antibody to recognize either biologically inactive CBG or structurally similar molecules. CBG-like binding activity, which appeared unrelated to glucocorticoid receptors, was also present in the endometrial cytosol of white crossbred gilts. Concentrations (fmol/mg protein) of endometrial CBG-like activity decreased (p = 0.03) between Days 10 and 15 of the estrous cycle and pregnancy, did not differ with reproductive status, and on Day 15 were comparable to concentrations in uterine flushings but threefold lower (p < 0.01) than those in the serum. Equilibrium dissociation constants for CBG-like binding activities were comparable among the three locations. These studies indicate that corticosteroids are present-primarily in the free form-within the porcine uterine lumen and could influence early porcine conceptus development. Endometrial CBG-like binding activity could mediate actions of cortisol or progesterone on uterine function.

Adrenal Cortex Hormones↗
PubMed2001

Corticosteroid-binding globulin status at the fetomaternal interface during human term pregnancy.

The status of the corticosteroid-binding globulin (CBG) at the fetomaternal interface, especially in the maternal intervillous blood space (I), was investigated and compared to that of CBG in the maternal (M) and fetal (umbilical arteries [A] and vein [V]) peripheral circulations at term. Immunoquantitation of plasma CBG showed that the CBG concentration in I was 30% less than that in M (P < 0.001) and threefold higher than that in umbilical cord blood (P < 0.001). The microheterogeneity of CBG studied by immunoaffinoelectrophoresis in the presence of concanavalin A and Western blotting indicated that the CBG in I was mainly of maternal origin and different from fetal CBG. A CBG mRNA, but no classic 50- to 59-kDa CBG, was found in isolated term trophoblastic cells. The steroid environment of the CBG in I differed greatly from that in the peripheral maternal and fetal circulations, because the progesterone:cortisol molar ratio in I was 75-fold higher than that in M and 7- to 10-fold higher than that in the fetal circulation. Binding studies revealed that the affinity constants of CBG for cortisol in I, A, and V were significantly lower than that in M plasma (P < 0.02) in their respective hormonal contexts. The binding parameters for I-CBG stripped of endogenous steroids and lipids were close to those for M-CBG but different from those of fetal CBG (P < 0.001). These data reflect the physiological relevance of the CBG-steroid interaction, especially with very CBG-loaded progesterone at the fetomaternal interface during late pregnancy.

Adult↗
PubMed1993

Hypercortisolism in septic shock is not suppressible by dexamethasone infusion.

OBJECTIVE: To explore the feedback regulation of glucocorticoids on corticotropin secretion in patients with septic and nonseptic circulatory shock. DESIGN: Prospective study. SETTING: An intensive care unit of a general hospital. PATIENTS: Two groups of patients with septic shock (n = 11) or nonseptic shock (n = 7). A control group (n = 20) was also studied. INTERVENTIONS: Intravenous dexamethasone (1 mg/hr for 4 hrs) suppression test. MEASUREMENTS: Plasma concentrations of corticotropin-releasing factor, beta-lipotropin, and corticosteroid-binding globulin measured by radioimmunoassays, and plasma cortisol measured by radiocompetition assay; the ratio of cortisol to corticosteroid-binding globulin calculated as the free cortisol index. MAIN RESULTS: In both groups of patients, the concentrations of plasma cortisol and beta-lipotropin, and the ratio of cortisol to corticosteroid-binding globulin, were higher than normal subjects (p < .001) and were not different between septic and nonseptic shock patients, whereas the plasma corticosteroid-binding globulin concentration was significantly (p < .001) lower in septic shock patients than in normal subjects (444 +/- 154 vs. 696 +/- 56 nmol/L [22.0 +/- 7.6 vs. 34.5 +/- 2.8 mg/L]), but not significantly lower in nonseptic shock patients (607 +/- 157 nmol/L [30.0 +/- 7.8 mg/L]). In contrast to the complete suppressive effect of dexamethasone infusion on cortisol and beta-lipotropin concentrations in normal subjects, dexamethasone did not suppress cortisol or lipotropin in either septic or nonseptic shock patients. CONCLUSIONS: During circulatory shock, hypercortisolism is associated with high concentrations of lipotropin, and is not suppressible by intravenous dexamethasone infusion.

Adult↗
PubMed1998

Decreased corticosteroid-binding globulin in burn patients: relationship with interleukin-6 and fat in nutritional support.

OBJECTIVES: To analyze the effect of low-fat nutritional solutions, with or without fish oil, on serum interleukin (IL)-6, and to explore the relationships between IL-6, corticosteroid-binding globulin (CBG; the main cortisol carrier in plasma), and protein metabolism in severely burned adult patients. DESIGN: Randomized, double-blind study with control and low fat-fed groups. SETTING: Burn center of Hôtel-Dieu Hospital of Montréal. PATIENTS: Thirty-seven men and women with thermal burn injury over >20% of body surface area and no other known medical condition. INTERVENTIONS: Within 24 hrs after admission, nutritional support was started through a gastroenteral tube inserted under endoscopic guidance. The goal for energy intake was calculated using the Curreri formula, and was adjusted with biweekly measurements of resting energy expenditure. Patients were randomly assigned to one of the following groups: control (35% of energy as fat); low fat 1 (15% of energy as fat); and low fat 2 (50% of fat in the form of fish oil). MEASUREMENTS AND MAIN RESULTS: Tumor necrosis factor (TNF)-alpha and TNF-beta, IL-6, CBG, and cortisol free fraction were measured every 3 days for 28 days. Nitrogen balance and urinary 3-methylhistidine excretion were measured daily. IL-6 concentrations were high in all patients, with the highest value (460 +/- 111 units/mL) observed on day 4. Concentrations of IL-6 were higher in control patients than in low fat-fed patients between days 13 and 28, but not between days 1 and 13. Multivariate analysis showed that IL-6, total body surface area burned, and sepsis scores were independent predictors of CBG between days 1 and 13 (n = 170; p<.00001). High IL-6 concentrations were predictors of low CBG concentrations and high cortisol free fractions. There was no relationship between IL-6, nitrogen balance, and 3-methylhistidine excretion. TNF-alpha and TNF-beta activity measurements by biological assay showed no correlation with other factors measured. CONCLUSIONS: a) Low-fat feeding, with or without fish oil, does not change the early production of IL-6 after burn injury; b) serum IL-6 is negatively correlated with CBG, which supports the hypothesis that this cytokine inhibits hepatic CBG production; and c) IL-6 does not appear to directly influence protein metabolism in burn patients.

Adult↗
PubMed1986

Suppression of testosterone-estradiol binding globulin by medroxyprogesterone acetate in polycystic ovary syndrome.

Serum androgen binding capacity is decreased in hirsute women and normal women receiving medroxyprogesterone acetate. A sensitive radioimmunoassay was used to measure the main androgen binding protein, testosterone-estradiol-binding globulin, in 13 patients with hirsutism and the polycystic ovary syndrome. Testosterone-estradiol-binding globulin concentrations were determined before, during, and after treatment with medroxyprogesterone acetate. Testosterone-estradiol-binding globulin was lower in untreated polycystic ovary syndrome patients than in normal controls (21.9 +/- 3.7 versus 64 +/- 4 nmol/L, P less than .01). Administration of medroxyprogesterone acetate (400 mg intramuscularly every 15 days for nine months) to polycystic ovary syndrome patients caused a decrease of serum testosterone and further lowering of testosterone-estradiol-binding globulin (7.6 +/- 1.9 nmol/L, P less than .01). In two patients the concentration of testosterone-estradiol-binding globulin reached values as low as 0.9 and 0.8 nmol/L, approximately 1/60 and 1/70 of the normal level. Testosterone-estradiol-binding globulin returned to basal levels (15.1 +/- 1.3 nmol/L) between one and two years after discontinuation of medroxyprogesterone acetate. Corticosteroid binding globulin levels were normal in polycystic ovary syndrome and did not change with medroxyprogesterone acetate. It was concluded that: medroxyprogesterone acetate causes marked lowering of plasma testosterone-estradiol-binding globulin; the effect is not mediated by sex hormone levels; and the decrease in testosterone-estradiol-binding globulin offsets, at least partially, the beneficial action of medroxyprogesterone acetate.

Female↗
PubMed1994

Delayed ACTH response to human corticotropin releasing hormone during cardiopulmonary bypass under diazepam-high dose fentanyl anaesthesia.

The inhibitory effect of high dose fentanyl (0.1 mg.kg-1) and diazepam (0.5 mg.kg-1) anaesthesia on the pituitary-adrenal response to coronary artery surgery during cardiopulmonary bypass was assessed by comparison of the adrenocorticotropic hormone and cortisol responses to intravenous boluses of either 0.1 mg (n = 14) or 0.2 mg (n = 14) human corticotropin releasing hormone administered 5 min after starting cardiopulmonary bypass, with the responses obtained in a control group (n = 14). Blood samples were taken before inducing anaesthesia, just before cardiopulmonary bypass and at 5, 20, 35, 50, 65 and 80 min thereafter. The administration of human corticotropin releasing hormone at both doses resulted in significantly greater plasma concentrations of adrenocorticotropic hormone at 50, 65 and 80 min compared to the control group; at the other sampling times there were no differences between the three groups. Plasma cortisol concentrations did not vary between the three groups at any sampling time. During cardiopulmonary bypass the early adrenocorticotropic responses to human corticotropin releasing hormone are blunted but later there is a good response, suggesting that the inhibitory effect of high dose fentanyl and diazepam anaesthesia takes place in the hypothalamus.

Adrenocorticotropic Hormone↗
PubMed1980

The dose-response relationship of ACTH and cortisol in Cushing's disease.

The dose-response relationship between plasma ACTH and plasma cortisol was examined in normal subjects, patients with Addison's disease and patients with Cushing's disease. Plasma cortisol and ACTH levels were measured every half-hour from 06.00 h to 10.00 h and from 16.00 h to 18.00 h during a control day and during 1 to 3 days of continuous cortisol infusion. A plot of mean morning plasma ACTH versus the log of mean plasma cortisol revealed a similar dose-response relationship in normal and Addisonian subjects. Total plasma cortisol was four times more potent in suppressing mean morning ACTH in normal and Addisonian subjects, than in patients with Cushing's disease. When plasma cortisol was undetectable, there was no significant difference between mean morning ACTH concentrations in Addisonian patients and in adrenalectomized Cushing's patients. The glucocorticoid feedback control of ACTH in Cushing's disease had dose-response characteristics similar to those in Addison's disease and normal subjects, except for decreased sensitivity to cortisol feedback suppression of ACTH.

Addison Disease↗
PubMed1981

Hormone binding globulin levels in patients with hereditary angiooedema during treatment with Danazol.

Five patients with hereditary angiooedema were treated with Danazol for periods up to 10 months. This therapy resulted in normalization of serum levels of the inhibitor of the first complement component and disappearance of clinical disease symptoms in all patients. Although a variety of hormones were measured, only those of the pituitary-gonadal axis altered during treatment: a moderate decrease in leuteinizing hormone levels and a sharp fall of testosterone in adult men were observed. In all patients, however, both sex hormone binding globulin and thyroxine binding globulin concentrations were considerably suppressed during Danazol therapy. However, levels of corticosterone binding globulin and thyroxine binding globulin concentrations were considerably suppressed during Danazol therapy. However, levels of corticosterone binding globulin remained unchanged. The fraction of endogenous testosterone not bound to sex hormone binding globulin invariably increased. The possible relevance of these findings to the understanding of the mode of action of Danazol both in these patients and in general, are discussed.

Adult↗
PubMed1984

Total deficiency of corticosteroid-binding globulin.

An obese 15-year-old boy of Jewish Iranian origin who is the offspring of consanguineous parents was found to have very low levels of total cortisol in the plasma. Investigation of the family revealed a complete lack of cortisol-binding-globulin (CBG) in the proband and a sister, evidently the first cases of total CBG deficiency to be reported. The parents and a brother were found to have half the normal levels. This study indicates that CBG deficiency, a benign condition, is compatible with a codominant or recessive autosomal trait inheritance.

Adolescent↗
PubMed1987

The effect of glucocorticoids on corticosteroid binding globulin.

To evaluate the effect of glucocorticoids on corticosteroid binding globulin (CBG), we measured the binding capacity and binding affinity of cortisol for CBG in normal subjects, patients receiving glucocorticoids and patients with Cushing's syndrome. Normal subjects had a mean binding capacity of 3.8 (+/- SD 0.7) X 10(-7) mol/l and mean binding affinity of 1.96 +/- 0.48 X 10(-8) M. Patients with Cushing's syndrome had a 40% decrease in binding capacity (2.3 +/- 0.4 X 10(-7) mol/l) compared to control subjects and significantly lower mean binding capacity than patients receiving pharmacological (2.9 +/- 0.6 X 10(-7) mol/l) and physiological doses of glucocorticoids (3.4 +/- 0.6 X 10(-7) mol/l) (P = 0.05 one-way analysis of variance). Patients with endogenous cortisol excess also had significantly lower mean binding affinity (1.54 +/- 0.37 X 10(-8) M) than normal subjects and glucocorticoid treated subjects. These changes suggest that both endogenous and exogenous glucocorticoids can modulate circulating levels of CBG and may have important implications for patients receiving steroid therapy.

Adrenal Insufficiency↗
PubMed1989

Effects of hyperthyroidism on binding proteins for steroid hormones.

Sex hormone binding globulin (SHBG) and corticosteroid binding globulin (CBG) binding capacities were examined weekly in eight normally cycling women and three women taking birth control pills during a 5-week baseline period and after daily ingestion of 75 micrograms of L-triiodothyronine (T3) for 30 days. The SHBG binding capacity increased whereas the CBG binding capacity decreased after T3 therapy. The binding capacities of proteins for steroid hormones were measured in 18 hyperthyroid subjects (Graves' disease) prior to and after 3 months of antithyroid drug therapy. SHBG binding capacity in hyperthyroid men or women was higher, and CBG binding capacity lower than those in euthyroid subjects. Thus, during hyperthyroidism, binding capacities of sex hormone binding globulin and corticosteroid binding globulin vary in opposite directions. A statistically significant correlation between the ratio of the sex hormone binding globulin to the corticosteroid binding globulin and triiodothyronine levels was found (P less than 0.01). Therefore the ratio of the sex hormone binding globulin to the corticosteroid binding globulin might be potentially useful as a biochemical index of thyroid hormone action in peripheral tissues.

Adult↗
PubMed1989

Corticosteroid-binding globulin in depression.

We undertook this study to evaluate the role of plasma free and total cortisol, and corticosteroid-binding globulin (CBG) in depression. Plasma was collected from 15 drug-free depressed patients and 15 age and sex-matched control subjects at 0900 and 2300 and at 1600 following an oral dose of dexamethasone. Depressed patients had elevated concentrations of both free and total cortisol at all time points studied. The binding capacity and affinity of plasma CBG for cortisol was similar in both groups at all times studied. No differences in CBG measures were noted if the depressed subjects were divided into elderly or younger subjects and dexamethasone suppression test (DST) suppressors or non-suppressors.

Aged↗
PubMed2006

Differences in cortisol concentrations in South Asian and European men living in the United Kingdom.

OBJECTIVE: The metabolic syndrome is more prevalent in South Asians in Britain than in the general population. Furthering our understanding of the underlying mechanisms is important because of the increased risk of cardiovascular disease associated with the metabolic syndrome. As it has been proposed that increased activity of the hypothalamic pituitary adrenal axis might underlie the metabolic syndrome, we hypothesized that plasma cortisol levels would be higher in South Asians and that increased cortisol levels would be associated with cardiovascular risk factors comprising the metabolic syndrome. The aim of the study was to examine ethnic differences in cortisol levels and to compare the relationships between cortisol levels and cardiovascular risk factors in men from different ethnic groups. DESIGN: Cross-sectional population-based study, Newcastle upon Tyne, UK. (Newcastle Heart project). Participants One hundred men, 40-67 years old, of European and South Asian (Indian, Pakistani, Bangladeshi) ancestry, with and without cardiovascular risk factors of the metabolic syndrome. MEASUREMENTS: Measurement of plasma cortisol and corticosteroid binding globulin in stored sera. RESULTS: After adjustment for age and the presence of cardiovascular risk factors, mean cortisol was 27% (95% CI, 10%, 40%) lower in South Asians compared to Europeans. Cortisol levels were higher in all men with cardiovascular risk factors than those without. CONCLUSIONS: Cortisol levels are lower in South Asian than in European men resident in the UK. Despite lower cortisol levels in South Asians, the relations between cortisol and cardiovascular risk factors remain strong.

Adult↗
PubMed1994

Hypothalamic-pituitary-adrenal activation following endotoxin administration in the developing rat: a CRH-mediated effect.

The present studies assessed hypothalamic-pituitary-adrenal (HPA) responses following immune activation with endotoxin (i.p.) in three-day old Long Evans rats. Marked plasma corticosterone (B), adrenocorticotrophic hormone (ACTH) responses and biphasic fluctuations in plasma glucose were maximal at a dose of 0.05 mg/kg. HPA responses peaked between 3-5 h following immune challenge and plasma ACTH and B responses were greater in female than in male rat pups. Plasma levels of corticosterone binding globulin (CBG) were reduced in males and substantially increased in females during the peak HPA response. Changes in plasma glucose were biphasic with slight increases when ACTH and B levels were maximal, but hypoglycemia was evident once plasma B levels returned to resting values. Endotoxin challenge reduced median eminence corticotropin-releasing hormone (CRH) levels at times corresponding with elevated HPA activity, and prior i.c.v. injection of the CRH antagonist, alpha-helical CRH, significantly attenuated elevations in plasma ACTH and B. In addition, alpha-helical CRH pretreatment completely blocked endotoxin-induced changes in plasma CBG in both males and females. These findings support the view that endotoxin-induced HPA activation in the neonate may occur via CRH.

Adrenal Glands↗