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PubMed1997

Dynamic microtubules and specification of the zebrafish embryonic axis.

BACKGROUND: The zebrafish is emerging as an important genetic system for the study of vertebrate development, and many zygotic mutations affecting embryogenesis have been isolated. The early events in development are under the control of maternal genes but are relatively unexplored. Here, the process of axis specification is investigated. RESULTS: The vegetal pole of the zygote transiently contains a dense array of parallel microtubules, while microtubules near the equator are disorganized. Irradiation of the zygote with ultraviolet light disrupts the formation of the vegetal microtubule array and causes loss of the axis; brief treatment with nocodazole at this stage also causes defects in the axis. During cleavage stages, yolk cortical microtubules reorganize to form arrays that apparently extend from marginal blastomeres. Prolonged exposure to cold (18 degrees C) or incubation in nocodazole prior to the 32-cell stage disrupts cortical microtubules and causes premature formation of the yolk syncytial layer; these treatments also prevent formation of an axis, as indicated by the absence of goosecoid and forkhead2 expression and of translocation of beta-catenin into nuclei. Cortical microtubule arrays are required for the transport of particles from the vegetal hemisphere into marginal blastomeres, as shown by the movement of polystyrene beads; treatments that prevent axis formation also prevent the entry of beads into blastomeres. CONCLUSIONS: To form an organizer, zebrafish blastomeres appear to require substances which are transported from the vegetal hemisphere of the yolk cell by cortical microtubules. Initial asymmetry appears dependent on an array of parallel microtubules at the vegetal pole.

Animals↗
PubMed2002

Effects of budesonide inhalation suspension on hypothalamic-pituitary-adrenal-axis function in infants and young children with persistent asthma.

BACKGROUND: The initial 12-week, double-blind phases of three studies demonstrated that budesonide inhalation suspension (BIS) is effective and well tolerated in infants and young children (6 months to 8 years of age) with persistent asthma. OBJECTIVE: Open-label, 52-week extensions to these studies were conducted to evaluate long-term safety of BIS, including effects of treatment with the lowest effective dose of BIS on hypothalamic-pituitary-adrenal (HPA)-axis function, as compared with conventional asthma therapy (CAT). Complete results of the earlier phases of the studies and of long-term safety are reported elsewhere; only results pertaining to HPA-axis function are summarized here. METHODS: Patients eligible for the open-label phases of the three trials were randomized to treatment with nebulized BIS (n = 447) or CAT (n = 223). CAT included short-acting oral or inhaled beta2-agonists, methylxanthines, or cromolyn sodium; in two of the studies, CAT could have included other inhaled corticosteroids. HPA-axis function, which had been evaluated during the 12-week double-blind studies, was again evaluated at the beginning and end of the 52-week study period using basal plasma cortisol concentrations and response to stimulation with a 250-microg dose of adrenocorticotropic hormone. RESULTS: There was no evidence of altered HPA-axis function attributable to BIS treatment. No clinically or statistically significant differences in basal or adrenocorticotropic hormone-stimulated plasma cortisol concentrations were observed between BIS and CAT in either the 12-week, double-blind or 52-week, open-label phases of the three studies. CONCLUSIONS: The results indicate that treatment with BIS does not result in clinically significant suppression of HPA-axis function in infants and young children.

Administration, Inhalation↗
PubMed2001

Suppression of hypothalamic-pituitary-adrenal axis activity with inhaled flunisolide and fluticasone propionate in adult asthma patients.

BACKGROUND: Suppression of the hypothalamic-pituitary-adrenal (HPA) axis, a potential systemic effect of inhaled corticosteroid therapy, can be quantified by monitoring serum, urinary, and salivary cortisol levels. OBJECTIVES: 1) Compare the effects on HPA axis of the inhaled corticosteroids flunisolide and fluticasone propionate versus placebo and oral prednisone. 2) Estimate dose-potency ratio for HPA-axis suppression. METHODS: Multicenter, randomized, placebo-controlled, open-label, 21-day trial. Active regimens were flunisolide 500 and 1,000 microg, twice daily; fluticasone propionate 110, 220, 330, and 440 microg, twice daily; and prednisone, 7.5 mg daily. Enrolled patients were nonsmokers, 18 to 50 years of age, with persistent mild-to-moderate asthma and had not used oral, nasal, or inhaled corticosteroids for 6 months before study. Main outcome measures were area under serum cortisol concentration curve for 22 hours (AUC(0-22h)); 24-hour urinary cortisol level; and 8 AM salivary cortisol level. RESULTS: One hundred fifty-three patients were randomly assigned to active treatment or placebo; 125 patients completed the study and were at least 80% compliant with their regimens. Both fluticasone propionate and flunisolide caused dose-dependent suppression of HPA axis, which was statistically greater for fluticasone propionate (P = 0.0003). Dose-potency ratio showed 4.4 times more serum-cortisol suppression/microgram increase in dose with fluticasone propionate than with flunisolide. Diurnal pattern of serum cortisol suppression was persistent with fluticasone propionate and "remitting" with flunisolide. Salivary and urinary cortisol data were qualitatively similar to serum cortisol results. CONCLUSIONS: Fluticasone caused significantly more suppression of HPA axis than flunisolide. Flunisolide may provide a safe option for patients with asthma requiring long-term inhaled corticosteroid therapy.

Administration, Inhalation↗
PubMed2004

Nodal and BMP2/4 signaling organizes the oral-aboral axis of the sea urchin embryo.

In the sea urchin embryo, the oral-aboral axis is specified after fertilization by mechanisms that are largely unknown. We report that early sea urchin embryos express Nodal and Antivin in the presumptive oral ectoderm and demonstrate that these genes control formation of the oral-aboral axis. Overexpression of nodal converted the whole ectoderm into oral ectoderm and induced ectopic expression of the orally expressed genes goosecoid, brachyury, BMP2/4, and antivin. Conversely, when the function of Nodal was blocked, by injection of an antisense Morpholino oligonucleotide or by injection of antivin mRNA, neither the oral nor the aboral ectoderm were specified. Injection of nodal mRNA into Nodal-deficient embryos induced an oral-aboral axis in a largely non-cell-autonomous manner. These observations suggest that the mechanisms responsible for patterning the oral-aboral axis of the sea urchin embryo may share similarities with mechanisms that pattern the dorsoventral axis of other deuterostomes.

Acebutolol↗
PubMed2006

CO2 challenge induced HPA axis activation in panic.

The hypothalamic-pituitary-adrenal axis (HPA axis) plays a critical role in stress management. Involvement of this physiological axis in the underlying mechanisms of panic disorder (PD) has been suggested. Studies using 35% CO(2) inhalation to provoke panic found no evidence for robust increases in cortisol levels in PD. However, cortisol levels alone may not be conclusive, as this hormone is merely the end product of a complex physiological axis. Sixteen PD patients and 16 healthy control subjects underwent a 35% CO(2) inhalation and a placebo inhalation on separate days according to a fixed order, double-blind design. Both serum and salivary cortisol, as well as adrenocorticotropic hormone (ACTH) were measured at regular time intervals. Cortisol and ACTH levels increased in the patient and control groups following 35% CO(2) inhalation. The magnitude of the increase was similar in patients and controls despite marked differences in anxiety. This study is the first to document a clear HPA response following 35% CO(2) inhalation in both PD patients and controls. This effect occurs independently of the specific panicogenic properties of the CO(2) challenge. It remains to be clarified whether panic is initially accompanied by major HPA axis activation or whether other stress-responsive systems underlie panic.

Administration, Inhalation↗
PubMed1996

Determination of the orientation of a band 3 affinity spin-label relative to the membrane normal axis of the human erythrocyte.

The orientation of the nitroxide moiety of an isotopically substituted spin-labeled derivative of dihydrostilbenedisulfonate ([15N,2H13]-SL-H2DADS-maleimide) covalently coupled at the extracellular stilbenedisulfonate binding site of the human erythrocyte anion exchange protein, band 3, has been determined relative to the membrane normal axis of intact cells. The X-band linear electron paramagnetic resonance (EPR) spectra of [15N,2H13]-SL-H2DADS-maleimide-labeled band 3 in intact erythrocytes oriented by flow through an EPR flat cell have been obtained for two orthogonal orientations of the sample in the DC magnetic field. Two different methods of analysis have provided very similar values for the angles alpha 1 and beta 1 which uniquely define the orientation of the nitroxide axis frame relative to the membrane normal axis. In the first approach, a variable fraction of the cells, f, were taken to be biconcave disks perfectly oriented relative to the flat cell surface with the remainder, 1-f, isotropically oriented. Simultaneous nonlinear least squares analysis of the spectra obtained at the two sample orientations yielded best fit values of f = 0.60, alpha 1 = 58 degrees, and beta 1 = 36 degrees. In the second approach, the EPR spectra of flow-oriented intact erythrocytes labeled with the fatty acid spin-label, [15N,2H12]-5-nitroxyl stearate, have been obtained at the two sample orientations. These two spectra have been used to determine a model-independent distribution of membrane normal orientations in the sample. Using this experimentally determined membrane normal orientation distribution, the EPR spectra of [15N,2H13]-SL-H2DADS-maleimide-labeled erythrocytes were then reanalyzed to obtain a second determination of the nitroxide orientation, alpha 1 = 61 degrees and beta 1 = 37 degrees. The orientation of the nitroxide with respect to the membrane normal axis determined in the present study is nearly identical to the orientation of the nitroxide with respect to the uniaxial rotational diffusion axis, alpha = 66 degrees and beta = 34 degrees, as determined from saturation transfer EPR (ST-EPR) studies [Hustedt, E. H., & Beth, A. H. (1995) Biophys. J. 69, 1409-1423]. This result supports the conclusion that the motion observed using ST-EPR spectroscopy is, in fact, the uniaxial rotational diffusion of band 3 about the membrane normal.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
PubMed2004

Uniaxial alignment of the smallest diamagnetic susceptibility axis using time-dependent magnetic fields.

A diamagnetic particle with magnetic susceptibilities chi3 < chi2 = chi1 < 0 was subjected to a rotating magnetic field to obtain an alignment of the chi3 axis (the smallest susceptibility axis) in the direction perpendicular to the plane of the rotating magnetic field. A polymer short fiber, whose fiber axis coincides with the chi3 axis, was suspended in a fluid with the same density, and then a rotating magnetic field generated by a rotation of a pair of permanent magnets was applied. The fiber axis, rotating following the applied field, finally ended up with an alignment perpendicular to the plane of the rotating magnetic field. The experimental data on the time course of the alignment was in good agreement with the numerical calculation based on the equation of rotation.

Journal Article↗
PubMed2003

The comorbidity of bipolar disorder and axis II personality disorders: prevalence and clinical correlates.

OBJECTIVES: Many studies have examined the prevalence and predictive validity of axis II personality disorders among unipolar depressed patients, but few have examined these issues among bipolar patients. The few studies that do exist suggest that axis II pathology complicates the diagnosis and course of bipolar disorder. This study examined the prevalence of axis II disorder in bipolar patients who were clinically remitted. METHODS: We assessed the co-occurrence of personality disorder among 52 remitted DSM-III-R bipolar patients using a structured diagnostic interview, the Personality Disorder Examination (PDE). RESULTS: Axis II disorders can be rated reliably among bipolar patients who are in remission. Co-diagnosis of personality disorder occurred in 28.8% of patients. Cluster B (dramatic, emotionally erratic) and cluster C (fearful, avoidant) personality disorders were more common than cluster A (odd, eccentric) disorders. Bipolar patients with personality disorders differed from bipolar patients without personality disorders in the severity of their residual mood symptoms, even during remission. CONCLUSIONS: When structured assessment of personality disorder is performed during a clinical remission, less than one in three bipolar patients meets full syndromal criteria for an axis II disorder. Examining rates of comorbid personality disorder in broad-based community samples of bipolar spectrum patients would further clarify the linkage between these sets of disorders.

Adolescent↗
PubMed2001

Hypothalamic-pituitary-adrenal axis activation by experimental periodontal disease in rats.

Organisms respond to inflammatory conditions by mounting a co-ordinated complex series of adaptive responses involving the immune, nervous and endocrine systems that are aimed at restoring the homeostatic balance. We have recently shown in a rat model that inappropriate hypothalamic-pituitary-adrenal (HPA) axis regulation and a subsequent inability to mount a suitable glucocorticoid response to gingival inflammation may influence susceptibility to periodontal disease. This study was designed to investigate whether ligature- and bacterial lipopolysaccharide (LPS)-induced inflammation in the gingival connective tissues may activate this physiological axis, and to further explore the significance of HPA regulation in periodontal disease. Experimental periodontal disease was induced in major histocompatibility complex (MHC)-identical but HPA low (LEW) and high (F344) responding rat strains. We tested (1) whether ongoing periodontal disease activates the HPA axis as measured by corticosterone levels, and (2) whether genetic differences in HPA regulation modulate periodontal disease progression. In the F344 strain. the periodontal tissue destruction was more severe. This observation was associated with a significant increase of corticosterone levels in F344 rats only. Addition of LPS at the gingival inflammatory site led to a further increase of corticosterone levels and disease severity in F344 rats. These findings illustrate a positive feedback loop between the HPA axis and periodontal disease: the disease activates the HPA axis, and a genetically determined high HPA responsivity further increases disease susceptibility.

Alveolar Bone Loss↗
PubMed1996

Initiation of vertebrate left-right axis formation by maternal Vg1.

In the development of the three-dimensional vertebrate body plan, the left-right axis is linked to the dorsoventral and anterioposterior axes. In humans, altered left-right development results in severe cardiovascular and visceral abnormalities in individuals and in conjoined twins. Although zygotically transcribed genes that are asymmetrically expressed have been identified, the mechanism by which left-right asymmetries are established during embryogenesis is unknown. Here we show that the Xenopus maternal gene Vg1, a member of the TGF-beta family of cell-signalling molecules which are implicated in dorsoanterior development, initiates left-right axis formation. Altered expression of Vg1 on the right side of 16-cell embryos or disruption of endogenous Vg1 signalling on the left side randomizes cardiac and visceral left-right orientation and alters expression of Xnr-1, a nodal-related molecular marker for left-right development. Furthermore, the orientation of the left-right axis in conjoined twins is dependent upon which cell-signalling molecule initiated twin formation and on whether the secondary axis is on the left or right side of the primary embryonic axis, implicating a molecular pathway leading to the formation of conjoined twins.

Activin Receptors↗
PubMed2006

The role of the VEGF-C/VEGFR-3 axis in cancer progression.

Vascular endothelial growth factor (VEGF) receptor 3 (VEGFR-3) (also called VEGFR-3) is activated by its specific ligand, VEGF-C, which promotes cancer progression. The VEGF-C/VEGFR-3 axis is expressed not only by lymphatic endothelial cells but also by a variety of human tumour cells. Activation of the VEGF-C/VEGFR-3 axis in lymphatic endothelial cells can facilitate metastasis by increasing the formation of lymphatic vessels (lymphangiogenesis) within and around tumours. The VEGF-C/VEGFR-3 axis plays a critical role in leukaemic cell proliferation, survival, and resistance to chemotherapy. Moreover, activation of the VEGF-C/VEGFR-3 axis in several types of solid tumours enhances cancer cell mobility and invasion capabilities, promoting cancer cell metastasis. In this review, we discuss the novel function and molecular mechanism of the VEGF-C/VEGFR-3 axis in cancer progression.

Disease Progression↗
PubMed1997

Leptin and the hypothalamic-pituitary-adrenal axis activity in women with different obesity phenotypes.

OBJECTIVE: Women with visceral obesity may have hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. Since glucocorticoids are involved in the expression of the ob gene, this study was carried out to investigate the relationship between serum leptin and the activity of the HPA axis in women with different obesity phenotypes. DESIGN: Cross sectional clinical study. SUBJECTS: Fifteen obese (Body Mass Index BM128 kg/m2) women and ten normal weight control women (BM126 kg/m2) were included in the study. MEASUREMENTS: Body fat distribution was defined by CT scan at the L4-L5 level. Baseline blood samples were obtained for hormone concentrations. The activity of the HPA axis was evaluated by measuring ACTH and cortisol blood levels after combined iv administration of corticotropin releasing factor (100 microg) + arginine-vasopressin (0.3 IU). RESULTS: Baseline cortisol, ACTH, and androgen levels were similar in all groups, whereas leptin levels were significantly higher in the obese groups than in normal weight controls, without any significant difference between women with different obesity phenotypes. Incremental areas of ACTH and cortisol were significantly higher in women with visceral obesity than in those with subcutaneous obesity and controls. No significant correlation was found between the activity of the HPA axis and leptin concentrations. Leptin showed a highly significant correlation with BMI and subcutaneous fat and a weak but significant correlation with visceral fat and the visceral-to-subcutaneous fat ratio. CONCLUSION: Women with different obesity phenotypes had similar serum leptin concentrations but different HPA axis activity, and there was no correlation between them.

Adrenocorticotropic Hormone↗
PubMed2003

Hyperforin-containing extracts of St John's wort fail to alter gene transcription in brain areas involved in HPA axis control in a long-term treatment regimen in rats.

We previously showed that a methanolic extract of St John's wort (SJW) (Hypericum) and hypericin, one of its active constituents, both have delayed regulation of genes that are involved in the control of the hypothalamic-pituitary-adrenal (HPA) axis. Hyperforin, another constituent of SJW, is active in vitro and has been proposed to be the active constituent for therapeutic efficacy in depression. We therefore examined if hyperforin has delayed effects on HPA axis control centers similar to those of Hypericum and hypericin. We used in situ hybridization histochemistry to examine in rats the effects of short-term (2 weeks) and long-term (8 weeks) oral administration of two hyperforin preparations, fluoxetine (positive control), and haloperidol (negative control) on the expression of genes involved in the regulation of the HPA axis. Fluoxetine (10 mg/kg) given daily for 8 weeks, but not 2 weeks, significantly decreased levels of corticotropin-releasing hormone (CRH) mRNA by 22% in the paraventricular nucleus (PVN) of the hypothalamus and tyrosine hydroxylase (TH) mRNA by 23% in the locus coeruleus. Fluoxetine increased levels of mineralocorticoid (MR) (17%), glucocorticoid (GR) (18%), and 5-HT(1A) receptor (21%) mRNAs in the hippocampus at 8, but not 2, weeks. Comparable to haloperidol (1 mg/kg), neither the hyperforin-rich CO(2) extract (27 mg/kg) nor hyperforin-trimethoxybenzoate (8 mg/kg) altered mRNA levels in brain structures relevant for HPA axis control at either time point. These data suggest that hyperforin and hyperforin derivatives are not involved in the regulation of genes that control HPA axis function.

Adrenal Glands↗
PubMed2003

Pharmacological and nonpharmacological factors influencing hypothalamic-pituitary-adrenocortical axis reactivity in acutely depressed psychiatric in-patients, measured by the Dex-CRH test.

The most consistent biological findings in patients with depression are abnormalities in the hypothalamic-pituitary-adrenal (HPA)-axis, which can be measured using the combined dexamethasone-suppression/CRH-stimulation (Dex-CRH) test. The reactivity of the HPA-axis in this test, however, ranges over several orders of magnitude in depressed patients with comparable severity of symptoms. In this present study, we investigate which factors influence the magnitude of the response in the Dex-CRH test in 235 acutely depressed in-patients. We first examined the effects of common confounders shown to influence the HPA-axis, such as caffeine and nicotine consumption, acute stressors during the test, weight, gender, and age. Of all these variables, only female sex and nicotine consumption were positively correlated with the cortisol or ACTH response, respectively. As for the effects of psychopharmacological treatment, only the intake of carbamazepine and the fact of having relapsed under an established pharmacotherapy significantly increased the response in the Dex-CRH test, whereas the presence or absence of antidepressant treatment, the type of antidepressant treatment, or the number of ineffective antidepressant treatment trials during the index episode up to admission did not have any effect. We also found a positive correlation of the number of previous episodes, the overall HAM-D score and the severity of somatic/vegetative symptoms with the results in the Dex-CRH test. These results underline that in depressed patients this test is not majorly influenced by disease-unrelated factors. In addition, current antidepressant treatment does not appear to affect test outcome in the absence of clinical response. The influence of the number of previous episodes and relapse under pharmacotherapy suggests that HPA-axis reactivity may be altered by repetitive states of hypercortisolemia or continuous antidepressant treatment. Finally, more severe vegetative symptoms are associated with an enhanced HPA-axis activity.

Adrenocorticotropic Hormone↗
PubMed1999

C-axis: a growth vector for the maxilla.

Based on M-point, defined as the center of the largest circle that is tangent to the superior, anterior, and palatal outlines of the maxilla in the sagittal view, a growth axis and its direction are described for each gender from age 7.4 to 18.75 years. Growth increments along the C-axis, defined by sella-M-point, are described by regression formulas with correlation coefficients of 0.618 for females and 0.669 for males. The vector (direction) of the growth axis, defined by the angle S-M-C-axis, increases in females from 42.21 degrees at 7.4 years to 44.47 degrees at 18.75 years, with a standard deviation of 3.55 degrees. In males, it increases from a mean of 41.69 degrees at 7.6 years to 45.55 degrees at 18.6 years, with a standard deviation of 2.74 degrees. This is based on 172 serial lateral cephalograms of 20 females and 174 serial lateral cephalograms of 19 males. The C-axis incremental growth change and its vector offer a means of quantifying complex maxillary growth in the sagittal plane via cephalometric measurements relative to and coordinated with other craniofacial structures.

Adolescent↗
PubMed2004

The G-Axis: a growth vector for the mandible.

On the basis of the G-point, defined as the center of the largest circle that is tangent to the internal inferior, anterior, and lingual surfaces of the mandibular symphysis in the sagittal view, a growth axis and its direction are described for each gender from age six to 19.25 years. Incremental growth along the G-Axis, defined by Sella-G-point, is described by regression formulas with correlation coefficients of 0.673 for female subjects and 0.749 for male subjects. The vector (direction) of the growth axis, defined by the angle alpha ((G-Axis)-(S-N)) does not materially alter in the age range studied. At age six in female subjects the angle alpha is 67.16 degrees +/- 3.03 degrees and at age 19.25 it is 66.87 degrees +/- 3.03 degrees, whereas in male subjects it is 66.12 degrees +/- 4.00 degrees and 67.93 degrees +/- 4.00 degrees, respectively. These changes and gender differences are not clinically significant. The data is based on 444 serial lateral cephalograms of 24 female subjects and 24 male subjects. The G-Axis incremental growth change and its vector offer an improved means of quantifying complex mandibular growth in the sagittal plane by using cephalometric measurements relative to and correlated with other craniofacial structures.

Adolescent↗
PubMed2005

Simulation study for a finite helical axis analysis of tooth movement.

The description of motion using a finite helical axis (FHA) is independent of the chosen coordinate system because the values of the helical axis parameters do not change with coordinate transformations. However, an intuitive understanding of tooth movement expressed by the FHA can be slightly difficult for orthodontists who have never used it. The purpose of this study was to clarify the basic behavior of the FHA to increase our understanding of the FHA during tooth movement. Parameters of the FHA were calculated in two different simulations of canine retraction. In simulation 1, as the tipping angle of the canine was increased from 5 degrees to 30 degrees, the direction vector of the FHA v approached the x-axis (tipping axis), thus increasing the rotation angle about the FHA theta. These results demonstrated that the direction vector of the FHA can indicate the axis of rotation that is most affected in three-dimensional transformation. In simulation 2, bodily tooth movement of the canine was increased from one to five mm, and the shortest distance from the origin to the FHA d increased in a linear manner. In this case, the percent increase in bodily tooth movement could be determined by the d value. This study showed that the use of FHA makes it possible to determine the torques applied to the tooth and the true bodily tooth movement during orthodontic treatment, and this may lead to a better understanding of how to move teeth.

Cuspid↗
PubMed2002

Perinatal malnutrition programs sympathoadrenal and hypothalamic-pituitary-adrenal axis responsiveness to restraint stress in adult male rats.

In humans, an altered control of cortisol secretion was reported in adult men born with a low birth weight making the hypothalamic-pituitary-adrenal (HPA) axis a possible primary target of early life programming. In rats, we have recently shown that maternal food restriction during late pregnancy induces both an intrauterine growth retardation and an overexposure of fetuses to maternal corticosterone, which disturb the development of the HPA axis in offspring. The first aim of this work was to investigate, in adult male rats, whether perinatal malnutrition has long-lasting effects on the HPA axis activity during both basal and stressful conditions. Moreover, as the HPA axis and sympathetic nervous system are both activated by stress, the second aim of this work was to investigate, in these rats, the adrenomedullary catecholaminergic system under basal and stressful conditions. This study was conducted on 4-month-old male rats malnourished during their perinatal life and on age-matched control animals. Under basal conditions, perinatal malnutrition reduced body weight and plasma corticosteroid-binding globulin (CBG) level but increased mineralocorticoid receptor (MR) gene expression in CA1 hippocampal area. After 30 min of restraint, perinatally malnourished (PM) rats showed increased plasma noradrenaline, adrenocorticotropin hormone (ACTH) and corticosterone concentrations similarly as controls, but calculated plasma-free corticosterone concentration was significantly higher and adrenaline level lower than controls. During the phase of recovery, PM rats showed a rapid return of plasma ACTH and corticosterone concentrations to baseline levels in comparison with controls. These data suggest that in PM rats, an elevation of basal concentrations of corticosterone, in face of reduced CBG and probably increased hippocampal MR lead to a much larger impact of corticosterone on target cells that mediate the negative-feedback mechanism on the activities of both the HPA axis and sympathoadrenal one.

Adrenal Glands↗