Free Corticosterone Levels Research Articles

Gestational age dependence of 11β-hydroxysteroid dehydrogenase and its relationship to the enzymes of phosphatidylcholine synthesis in lung and liver of fetal rat

Increase in fetal surfactant synthesis and lung maturity is caused by the glucocorticoidal induction of enzymes required for phosphatidylcholine (PC) synthesis towards the end of gestation. The regulation of gestational age-dependent induction of PC synthesis by glucocorticoids is still unclear. Since 11-β-hydroxysteroid dehydrogenase (11β-HSD) activity and its metabolising capacity for glucocorticoids have been suggested to play a central role in this regulation, we measured the gestational age-dependent changes in 11β-HSD and PC synthesizing enzymes in lung and liver of fetal rat. The activity of cholinephosphate cytidyltransferase (CCT; key enzyme in PC synthesis), choline phosphotransferase (CPT) and lysolecithin acyltransferase (LAT) were found to increase gradually in the lung towards the end of gestation, reached peak values at term followed by a decrease of activity reaching finally adult levels. Only CK activity exhibited constant levels until term followed by a slight increase after the birth. In comparison with the lung, the liver enzymes followed a similar pattern, but at a higher rate of activity except for CCT which was higher in the lung. The activity of 11β-HSD in fetal lung microsomes was detectable from day 20 and increased towards the end of gestation in the lung and liver of the rat. Oxidase activity was always found to exceed the reductase activity. The activity of 11β-HSD continued to increase after delivery and reached peak levels in adult animals in both organs. In order to test the hypothesis, whether 11β-HSD activity and PC synthesis are induced by increasing endogenous glucocorticoidal levels, we examined on day 19 of gestation the effect of dexamethasone (DEXA) on enzymatic activities (11β-HSD, CCT) and on [ 14C]choline incorporation in phosphatidylcholine in fetal lung organoid cultures. Additionally, changes in CCT activity in fetal lungs after maternal administration of DEXA were measured. DEXA accelerated 11β-HSD and CCT activities as well as [ 14C]choline incorporation. We conclude, that endogenous glucocorticoids induce PC synthesis as well as 11β-HSD activity in lung and liver of the fetal rat. Fetal PC synthesis is not altered by increasing 11β-HSD levels, because the increase of free serum corticosterone levels apparently exceeds the metabolising capacity of 11β-HSD towards term.

Spring Declines in Microtus pennsylvanicus and the Role of Steroid Hormones

Spring declines are a common feature of small mammal demography. We tested the hypothesis that meadow voles from populations experiencing severe spring declines should exhibit severe stress responses as indicated by high free corticosterone levels. Three populations in southern Ontario were live-trapped intensively in the spring of 1985, all animals were bled each time, and measurements of total corticosterone, corticosterone-binding globulin (CBG), and total androgen (testosterone and dihydrotestosterone) were obtained by radioimmunoassay

Bombesin-induced hypothermia and hypophagia are associated with plasma metabolic fuel alterations in the rat

Microinfusion of bombesin into the preoptic area (POA) has previously been shown to reduce core body temperature and feeding in rats that are food-deprived or made hypoglycemic with insulin. The present study determined the metabolic fuel state of rats under these experimental conditions. In addition, changes in plasma metabolic fuels following the microinfusion of bombesin (50 ng/0.25 μl) into the POA were evaluated. Rats ( n = 8) were tested under conditions of food satiation, food deprivation (20 h), and insulin pretreatment (10 U/kg). Prior to peptide infusion, food-deprived rats exhibited the expected elevation in free fatty acids coupled with a small decline in plasma glucose. Insulin treatment resulted in hypoglycemia which persisted for at least 120 min. Following bombesin infusion, free fatty acids and corticosterone levels were elevated in food-sated rats. Food-deprived rats exhibited elevation in plasma glucose, free fatty acids, and corticosterone following peptide infusion. In insulin-treated rats, bombesin attenuated the hypoglycemia observed in controls and increased corticosterone levels. These findings suggest that bombesin-like peptides localized within the POA may participate in the regulation of metabolic fuels.

Population Ecology and Physiology of the Common Rock Rat, Zyzomys argurus (Rodentia: Muridae) in Tropical Northwestern Australia

The common rock rat, Zyzomys argurus , undergoes a marked seasonal change in abundance in rocky habitats of tropical Australia. Four local populations had highest numbers between the late-dry (September) and mid-wet (January) periods before undergoing a three- to four-fold decrease by the end of the wet season (April). Densities differed between these populations; one population disappeared in April. Immature individuals were more abundant in September when recruitment appeared maximal; the population decline is attributable to mortality in all age categories. Both sexes were reproductively active throughout the year, but pregnant females were most abundant in April. Litter size ranged from one to six and heavier females had more embryos. Gene frequencies of Z. argurus were significantly different between the wet (January and April) and dry (July and September) seasons and the ephemeral population had different gene frequencies from the others. Differences also occurred in concentration of plasma corticosterone, maximum corticosterone-binding capacity, and corticosteroid-binding globulin-bound corticosterone. In January, individuals in all local populations had normal body weight and albumin levels, and enlarged tail bases (a fat store). They also had elevated levels of free corticosterone, neutrophils, incidence of Salmonella , and total leucocyte count; lymphocyte to neutrophil ratios differed between populations. These data indicate that populations at differing densities and in average nutritional state had greater levels of physiological and pathological stress factors in the wet season suggesting that exogenous rather than endogenous factors control stress.

Normal levels of serum corticosterone and hepatic glucocorticoid receptors in obese (fa/fa) rats.

In an attempt to understand the hyper-responsiveness to glucocorticoids that is characteristic of genetically obese fa/fa rats, we have measured the levels of free corticosterone in serum from lean and obese rats as well as the number of "cytosolic" and "nuclear" binding sites in livers of these rats. Both the lean and obese rats had similar amounts of free corticosterone available for biological activity at 4 weeks and 10 weeks of age. Measurement of glucocorticoid binding to hepatic glucocorticoid receptors failed to show any differences between genotypes leading to the suggestion that the abnormal glucocorticoid response in obese rats may be due either to post-receptor defects or to a permissive action of the steroid in the expression of the fa/fa genotype.

Role of noradrenergic neurons in ethanol-induced elevation of free fatty acids and corticosterone

The effects of ethanol (2 or 3 g/kg) on plasma corticosterone and free fatty acids were examined in rats with bilateral electrolytic lesions of locus coeruleus or pretreated with the noradrenergic neurotoxin DSP 4 (50 mg/kg). Both lesions and DSP 4 significantly attenuated ethanol induced elevation of free fatty acids. No changes in basal levels of free fatty acids or corticosterone were observed nor did either treatment alter the elevating effect of ethanol on corticosterone. The results indicate that ethanol alters plasma free fatty acids through mechanisms involving noradrenergic neurons in the central nervous system.

A direct method for determination of the time integral of corticosterone availability in interstitial fluid of rats

A novel method for direct determination of the time integral of free corticosterone levels in interstitial fluid was used to measure corticosterone availability at rest and during free-operant shock-avoidance (SA) training in male rats. The method employs a subcutaneously implanted device to continuously accumulate the free hormone at a rate proportional to local concentration. The proportional rate of accumulation is maintained by providing mass-action corticosterone binding capacity within the device such that the device establishes a diffusion gradient for free corticosterone. The rate of uptake is limited so as to avoid disturbing equilibrium between free and bound hormone in the environment of the device. Corticosterone accumulation increased to 3× baseline during SA and was dexamethasone suppressible. These findings demonstrate the utility of a method uniquely combining specific measurement of free hormone with time integration to yield estimates of hormone availability during behavioral performance by an untethered subject. The method is suggested to be applicable to measurement of an extremely wide variety of drugs and hormones, under generally nonconstraining conditions.

Phase shifts in circadian rhythmicity of total, free corticosterone and transcortine plasma levels in hypothyroid male Japanese quails

Control, radiothyroidectomized, and methimasol-treated short day (6L:18D; beginning of light at 0700) male Japanese quails were studied with regard to their circadian rhythmicity of total, free corticosterone and transcortine plasma level. In the controls, the peak of total and free corticosterone coincided with the maximal corticosterone binding capacity of transcortine; these parameters can be characterized by similar daily rhythm. In hypothyroid birds a synchronous phase shift of these parameters has been observed. In methimasol-treated animals the phase shift of the circadian rhythmicity was 6–8 hr, and in the radiothyrodectomized group 12 hr, respectively. According to the degree of hypothyroidism the metabolic clearance rate (MCR) of corticosterone decreased. This effect leads to the phase shift of total corticosterone rhythm, and the shift includes not only free, but also transcortine concentration.

Effects of maternal diabetes on the development of carbohydrate metabolizing enzymes in fetal rat liver

Effects of streptozotocin-induced maternal diabetes on fetal hepatic carbohydrate-metabolizing enzyme development and hormonal status has been explored in the rat. Hepatic glycogen synthase a activity of the normal fetus rose to a maximum at 20 days of gestation, then fell prior to parturition. In fetuses of diabetic mothers, this prepartum decline was curtailed, resulting in enhanced synthase a activity and increased glycogen content in fetal livers at term. Elevation in hepatic synthase a in fetuses of diabetic mothers was due, not to altered interconversion between existing synthase a and b, but to equivalent increases in both forms of the enzyme. Both hepatic and free plasma corticosterone levels were elevated in fetuses of diabetic mothers and may be responsible for the enhanced development of total glycogen synthase observed in these fetuses. In normal fetuses hepatic phosphofructokinase and pyruvate kinase activities also rose to maxima at 20 days, then declined prior to term. In fetuses of diabetic mothers pyruvate kinase activity attained higher than normal maximal levels and phosphofructokinase activity fell more gradually, thus resulting in elevations in both enzyme activities at term. Augmentations in these glycolytic enzymes are compatible with hyperinsulinemia observed in fetuses of diabetic mothers. The following conclusions may be drawn from these findings. During late fetal life developmental patterns of rate-limiting hepatic glycogen-synthesizing and glycolytic enzymes are adapted to glucose utilization. In the normal fetus these patterns reverse at term, thereby promoting glucose mobilization, which prepares the fetus for abrupt deprivation of maternal glucose at birth. Maternal diabetes results in retardation of these reversal processes, presumably due to elevations in fetal glucocorticoid and insulin levels. Glycogenolytic and glucogenic capacities are thereby impaired in these fetuses.

Status of the Pituitary-Adrenocortical-Liver Axis following Partial Hepatectomy

AbstractSince the liver is the primary site of steroid degradation and plasma binding protein synthesis, studies were undertaken to evaluate adrenocortical activity in partially hepatectomized (H) male rats. Two days after either 10, 30, 40, or 70% H, significant decreases in liver mass were observed, while elevations in total and free plasma corticosterone levels, adrenal corticosterone content, and adrenal weights were noted only in the 70% H group. Hepatic δ4-steroid hydrogenase activity was significantly depressed in both whole and microsomal, but not in the supernatant, fractions of the regenerating liver of the 70% H group. Although plasma ACTH levels were unchanged in these animals, the in vitro adrenocortical responsiveness to ACTH was increased. These data suggest that a portion of the increase in total plasma corticosterone levels post-70% H was due to a reduction in the hepatic capacity to inactivate corticosterone, while the remainder may be due to an increase in adrenocortical secretion as a ...

5 - Steroidogenesis in the Postmenopausal Ovary

Sex differences exist for stress reactivity as well as for the prevalence of depression, which is more frequent in women of reproductive age and often precipitated by stressful events. In animals, the differential effect of stress on male's and female's emotional behavior has been well documented. Crosstalk between the gonadal and stress hormones, in particular between estrogens and glucocorticoids, underlie these sex differences on stress vulnerability.We have previously shown that corticosteroid binding globulin (CBG) deficiency in a mouse model (Cbg k.o.) leads, in males, to an increased despair-like behavior caused by suboptimal corticosterone stress response. Because CBG displays a sexual dimorphism and is regulated by estrogens, we have now investigated whether it plays a role in the sex differences observed for emotional reactivity in mice.By analyzing Cbg k.o. and wild-type (WT) animals of both sexes, we detected sex differences in despair-like behavior in WT mice but not in Cbg k.o. animals. We showed through ovariectomy and estradiol (E2) replacement that E2 levels explain the sex differences found in WT animals. However, the manipulation of E2 levels did not affect the emotional behavior of Cbg k.o. females. As Cbg k.o. males, Cbg k.o. females have markedly reduced corticosterone levels across the circadian cycle and also after stress. Plasma free corticosterone levels in Cbg k.o. mice measured immediately after stress were blunted in both sexes compared to WT mice. A trend for higher mean levels of ACTH in Cbg k.o. mice was found for both sexes. The turnover of a corticosterone bolus was increased in Cbg k.o. Finally, the glucocorticoid-regulated immediate early gene early growth response 1 (Egr1) showed a blunted mRNA expression in the hippocampus of Cbg k.o. mutants while mineralocorticoid and glucocorticoid receptors presented sex differences but equivalent mRNA expression between genotypes.Thus, in our experimental conditions, sex differences for despair-like behavior in WT mice are explained by estrogens levels. Also, in both sexes, the presence of CBG is required to attain optimal glucocorticoid concentrations and normal emotional reactivity, although in females this is apparent only under low E2 concentrations. These findings suggest a complex interaction of CBG and E2 on emotional reactivity in females.

Chick embryonic plasma proteins and binding capacity for corticosterone

Plasma was collected from White Leghorn embryos on alternate days from Day 4 of incubation to Day 22 (day after hatch). The plasma-binding capacity for corticosteroid was essentially zero before Day 10, but rose rapidly between Days 10 and 12. Binding capacity remained high until Day 16 and then declined before hatch. The increase after Day 10 was concurrent with the appearance of α-globulin whose rate of migration on acrylamide gel electrophoresis was similar to that of purified chicken corticosteroid binding globulin. Corticosterone, which was present in the plasma of the 4-day embryo, rose to its highest level on Day 20. The relatively high corticosterone concentration, with low plasma-binding capacity, suggests that in the chick embryo levels of free or active corticosterone are highest before Day 10 and just prior to hatching.

Adrenal function and the effect of a high-fat diet on C57BL/6J and C57BL/6J-ob/ob mice.

In C57BL/6J mice and the ob/+ and ob/ob mutants total plasma corticosterone levels were found to be statistically different. In C57BL/6J mice the level was 1.9 +/- 0.2 mug/100 ml plasma, in ob/+ mice 8.6 +/- 1.6 mug/100 ml and in ob/ob mice 13.7 +/- 1.5 mug/100 ml. The percentage of protein-bound corticosterone as well as the free endogenous corticosterone levels were also different. Feeding a high-fat diet to young C57BL/6J and C57BL/6J-ob/ob mice for a period of 4 weeks had no effect upon blood glucose, plasma insulin and plasma corticosterone levels. The significantly higher increase in body weight of the high-fat diet groups of both lines of mice was mainly due to fat cell hypertrophy.

The significance of the antidiuretic hormone in the release mechanism of corticotropin.

In posterior lobectomized rats the antidiurctic response to hemorrhage, histamine injection and a painful stimulus is markedly depressed. Exposure of such animals to “systemic” stress such as hemorrhage under ether anesthesia, histamine and nicotine injection elicits an increase in plasma free corticosterone levels similar to that found in sham operated controls. The increment in plasma free corticosterone following “neurogenic” stress such as strange environment, sound and pain is significantly reduced. A distinct adrenal hypertrophy is found in posterior lobectomized rats. However, the sensitivit of these adrenals is similar to that of sham operated controls. Treatment of posterior lobectomized rats with 1 unit of Pitrcssin tannate for 5 consecutive days decreases water intake to that of intact controls, induces the accumulation of neurosecretory material in the infundibular stem, normalizes adrenal weight and simultaneously restores pituitary response to neurogenic stimuli in posterior lobectomized rat...