Corticosteroid-binding globulin (CBG) in fetal development

Challis, John; Berdusco, E. T. M.; Jeffray, T; Yang, Kaiping; Hammond, Geoffrey L.

doi:10.1016/0960-0760(95)00100-e

Cited by 28 publications

(13 citation statements)

References 22 publications

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“…In addition, corticosteroidinduced expression of CBG in mouse liver around embryonic day 15 (E15) to E16 (5,27,38) and in mouse kidney around birth (26) suggested distinct roles for the carrier in maturation of these organs in rodents. These functions were proposed to involve regulation of systemic glucocorticoid metabolism or local delivery of steroids via membrane receptors identified in embryonic tissues (5). Normal perinatal survival of the cbg Ϫ/Ϫ animals already indicated unimpaired maturation of the lung.…”

Section: Resultsmentioning

confidence: 99%

“…An alternative mode of local delivery of steroid hormones is suggested by the identification of surface binding sites for CBG in a number of steroid target tissues, such as liver, endometrium, and spleen (14,15,30,34), suggesting the existence of membrane receptors for cellular uptake and/or transmembrane signaling of CBG/steroid complexes. Finally, a role for the protein in embryonic development of the kidney and liver has been proposed based on the spatially and temporarily restricted expression of the carrier in these tissues during development (5,26,27).…”

mentioning

confidence: 99%

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Hyporesponsiveness to Glucocorticoids in Mice Genetically Deficient for the Corticosteroid Binding Globulin

Petersen

Andreassen

Breiderhoff

et al. 2006

Molecular and Cellular Biology

112

104

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Corticosteroid binding globulin (CBG) is the carrier for glucocorticoids in plasma. The protein is believed to keep the steroids inactive and to regulate the amount of free hormone acting on target tissues (free hormone hypothesis). Here, we generated a mouse model genetically deficient for CBG to test the contribution of the carrier to glucocorticoid action and adrenocortical stress response. The absence of CBG resulted in a lack of corticosterone binding activity in serum and in an ϳ10-fold increase in free corticosterone levels in CBG-null mice, consistent with its role in regulation of circulating free hormone levels. Surprisingly, cbg ؊/؊ animals did not exhibit features seen in organisms with enhanced glucocorticoid signaling. Rather, the mice exhibited increased activity of the pituitary axis of hormonal control, normal levels of gluconeogenetic enzymes, and fatigue, as well as an aggravated response to septic shock, indicating an inability to appropriately respond to the excess free corticosterone in the absence of CBG. Thus, our data suggest an active role for CBG in bioavailability, local delivery, and/or cellular signal transduction of glucocorticoids that extends beyond a function as a mere cargo transporter.

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Hyporesponsiveness to Glucocorticoids in Mice Genetically Deficient for the Corticosteroid Binding Globulin

Petersen

Andreassen

Breiderhoff

et al. 2006

Molecular and Cellular Biology

112

104

View full text Add to dashboard Cite

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“…Secondly, the placenta in some species can both produce corticotrophin-releasing factor, stimulating fetal HPA axis development (Florio et al 2002), and further act as a control point for maternal GC entry into the fetal compartment through the expression and activity of the two 11b-hydroxysteroid dehydrogenase (11b-HSD) isoforms 1 and 2 (Seckl 1997). In addition, further levels of complexity in the axis exist in the form of binding globulins, which prevent access of GC to the GC receptor (Challis et al 1995) and the developing regional-specific tissue expression of 11b-HSD within the fetus (Seckl & Chapman 1997. Consequently, the initial response of maternal-fetal HPA axes to maternal (perhaps fetal) undernutrition has only been partially described and appears gestational age-dependent.…”

Section: Discussionmentioning

confidence: 99%

Effect of periconceptional undernutrition and gender on hypothalamic–pituitary–adrenal axis function in young adult sheep

Gardner¹,

Bon²,

Dandrea

et al. 2006

Journal of Endocrinology

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Glucocorticoids are proposed to act as intermediary factors that transcribe the developmental programming sequelae of maternal nutrient restriction (NR). Periconceptional undernutrition of sheep markedly activates fetal hypothalamicpituitary-adrenal (HPA) axis activity leading to preterm birth, while transient undernutrition during late gestation in sheep programs adult HPA axis function. To date, no study has examined resting or stimulated HPA axis function in young adult offspring following a periconceptional nutritional challenge. In the present study, 20 ewes were either periconceptionally undernourished (50% metabolisable energy requirements from days 1 to 30 gestation; NR, nZ8) or fed to control levels (100% requirement; controls, nZ12) to term (147 days gestation). Ewes were blood sampled remotely at 2 and 30 days using automated blood sampling equipment. Thereafter, offspring (controls, nZ6/6 males/females; NR, nZ4/4 males/females) were reared to 1 year of age and on separate days received either an i.v. corticotrophin-releasing hormone (CRH; 0$5 mg/kg) and vasopressin (AVP; 0$1 mg/kg) challenge or a synthetic ACTH i.v. bolus (Synacthen; 1$25 mg/kg), and blood samples were taken (manually and remotely) at appropriate intervals for measurement of plasma ACTH and cortisol accordingly. Resting plasma cortisol, assessed remotely, was similar in ewes during undernutrition (control 18$3G1$4 vs NR 23$4G1$9 nmol/l) and in offspring at 4 months of age (control male 17$6G2$9; control female 17$2G0$4, NR male 16$5G3$1, NR female 21$7G4$0 nmol/l). At 12 months of age, however, resting plasma cortisol was significantly increased in NR females (control male 28$0G1$5, control female 32$9G9, NR male 32G7, NR female 53G10 nmol/l, F 5$7, PZ0$02) despite no difference in plasma ACTH concentration. There was an interaction between nutritional group and gender for both the pituitary and adrenal responses to CRH and AVP, i.e. for controls, females exhibited increased plasma ACTH or cortisol relative to males but for NR this trend was either not present or reversed. The adrenocortical response to synthetic ACTH was gender-dependent only, being greater in female offspring. Combined CRH and AVP provoked a transient hypertension and marked bradycardia in all animals, irrespective of dietary group or gender and could be effectively reproduced by an AVP bolus alone. In conclusion, the present study has shown that periconceptional undernutrition of sheep has only a minor influence on HPA axis function in their young adult offspring when considered alongside the effect of gender per se.

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“…Concomitant reductions in negativefeedback-induced suppression of further ACTH release during stress would occur, and result in a greater plasma ACTH response to severe stressors. In addition, our test of efficacy of negative-feedback using dexamethasone was designed to test for differences in feedback induced by changes in GR, primarily in the pituitary gland (McEwen 1977, Challis et al 1995. The use of dexamethasone Figure 3 Handled boars had greater plasma ACTH concentrations when they were killed at 7 months of age.…”

Section: Discussionmentioning

confidence: 99%

Neonatal handling permanently alters hypothalamic-pituitary- adrenal axis function, behaviour, and body weight in boars

Weaver¹,

Aherne²,

Meaney³

et al. 2000

Journal of Endocrinology

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Neonatal handling permanently alters hypothalamicpituitary-adrenal axis (HPA) function in rats. In the rat, this treatment increases hippocampal glucocorticoid receptors (GR) and dampens plasma ACTH and corticosterone responses to stressors. The objectives of this study were to determine whether neonatal handling of pigs would effect permanent changes in plasma corticosteroid binding capacity (CBG), basal or stressor-induced plasma cortisol and ACTH concentrations, brain or pituitary GR levels, dexamethasone suppression of plasma cortisol and ACTH concentrations, behaviour in an open field-test pen, and body weights. Twelve litters of pigs were randomly assigned to either neonatal handling or no disturbance. Handled litters were removed from the farrowing crate for 10 min per day for the first 14 days of life. Male pigs were kept for the study and the boars were weighed monthly. At 7 months of age, boars were tested for locomotory behaviour in an open field-test pen. The boars were implanted with indwelling ear-vein catheters and blood samples were obtained basally, during and after application of a nose snare, and after 0·04 mg/kg dexamethasone. Boars were killed and blood samples were obtained and the brain and pituitary glands collected. Handled boars had greater (P<0·05) plasma CBG binding and lower basal total (P<0·05) and calculated free (P<0·03) plasma cortisol concentrations. No significant differences between treatments were found in plasma ACTH or cortisol responses to a nose-snare stressor; however, when killed, handled boars had greater (P<0·02) plasma ACTH concentrations. Handled and non-handled boars did not differ in plasma ACTH or cortisol responses to dexamethasone. There was no treatment effect on GR expression in the pituitary gland, frontal cortex, hippocampus, or hypothalamus. Behaviourally, the handled boars had higher (P<0·03) locomotor scores over inner squares and a lower (P<0·05) ratio of outer:inner squares entered in open field-tests. During the first 7 months of life, body weights were lower (P<0·004) for handled boars. In conclusion, neonatal handling permanently altered HPA function in pigs, but in a manner dissimilar to that found in the rat. These changes induced in the pig were not beneficial for commercial production with respect to body weight.

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Corticosteroid-binding globulin (CBG) in fetal development

Cited by 28 publications

References 22 publications

Hyporesponsiveness to Glucocorticoids in Mice Genetically Deficient for the Corticosteroid Binding Globulin

Hyporesponsiveness to Glucocorticoids in Mice Genetically Deficient for the Corticosteroid Binding Globulin

Effect of periconceptional undernutrition and gender on hypothalamic–pituitary–adrenal axis function in young adult sheep

Neonatal handling permanently alters hypothalamic-pituitary- adrenal axis function, behaviour, and body weight in boars

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