SEARCH · PubMed Health

Results for “AXIS”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,045 records · Page 58Linked to original sources

PubMed1998

Axis I comorbidity of borderline personality disorder.

OBJECTIVE: The purpose of this study was to assess the lifetime rates of occurrence of a full range of DSM-III-R axis I disorders in a group of patients with criteria-defined borderline personality disorder and comparison subjects with other personality disorders. METHOD: The axis I comorbidity of 504 inpatients with personality disorders was assessed by interviewers who were blind to clinical diagnosis and who used a semistructured research interview of demonstrated reliability. RESULTS: Four new findings emerged from this study. First, anxiety disorders were found to be almost as common among borderline patients (N=379) as mood disorders but far more discriminating from axis II comparison subjects (N=125). Second, posttraumatic stress disorder (PTSD) was found to be a common but not universal comorbid disorder among borderline patients, a finding inconsistent with the view that borderline personality disorder is actually a form of chronic PTSD. Third, male and female borderline patients were found to differ in the type of disorder of impulse in which they "specialized." More specifically, substance use disorders were significantly more common among male borderline patients, while eating disorders were significantly more common among female borderline patients. Fourth, a lifetime pattern of complex comorbidity (i.e., met DSM-III-R criteria for both a disorder of affect and a disorder of impulse at some point before the patients' index admission) was found to have strong positive predictive power for the borderline diagnosis as well as a high degree of sensitivity and specificity. CONCLUSIONS: These results suggest that the lifetime pattern of axis I comorbidity characteristic of borderline patients and distinguishing for the disorder is a particularly good marker for borderline personality disorder.

Adolescent↗

PubMed1998

Limitations of axis II in diagnosing personality pathology in clinical practice.

OBJECTIVE: DSM-IV's axis II is limited to severe personality disturbances, posing difficulty for diagnosing less severe but nonetheless clinically significant personality pathology. The authors examined the percentage of patients treated in clinical practice for personality pathology who are diagnosable with DSM-IV. METHOD: Psychiatrists and psychologists from a random national sample provided diagnostic data on 714 patients treated for enduring, maladaptive personality patterns. RESULTS: Only 39.4% of the patients had diagnosable axis II disorders. This percentage was relatively stable across clinicians' theoretical orientations and did not vary substantially when axis I diagnosis was controlled for. CONCLUSIONS: DSM-IV cannot be used to diagnose most patients being treated for personality problems. The range of axis II should be broadened to encompass the range of personality pathology seen in clinical practice.

Adult↗

PubMed2002

Axis I and II psychiatric disorders after traumatic brain injury: a 30-year follow-up study.

OBJECTIVE: Patients who had suffered traumatic brain injury were evaluated to determine the occurrence of psychiatric disorders during a 30-year follow-up. METHOD: Sixty patients were assessed on average 30 years after traumatic brain injury. DSM-IV axis I disorders were diagnosed on a clinical basis with the aid of the Schedules for Clinical Assessment in Neuropsychiatry (version 2.1), and axis II disorders were diagnosed with the Structured Clinical Interview for DSM-III-R Personality Disorders. Cognitive impairment was measured with a neuropsychological test battery and the Mini-Mental State Examination. RESULTS: Of the 60 patients, 29 (48.3%) had had an axis I disorder that began after traumatic brain injury, and 37 (61.7%) had had an axis I disorder during their lifetimes. The most common novel disorders after traumatic brain injury were major depression (26.7%), alcohol abuse or dependence (11.7%), panic disorder (8.3%), specific phobia (8.3%), and psychotic disorders (6.7%). Fourteen patients (23.3%) had at least one personality disorder. The most prevalent individual disorders were avoidant (15.0%), paranoid (8.3%), and schizoid (6.7%) personality disorders. Nine patients (15.0%) had DSM-III-R organic personality syndrome. CONCLUSIONS: The results suggest that traumatic brain injury may cause decades-lasting vulnerability to psychiatric illness in some individuals. Traumatic brain injury seems to make patients particularly susceptible to depressive episodes, delusional disorder, and personality disturbances. The high rate of psychiatric disorders found in this study emphasizes the importance of psychiatric follow-up after traumatic brain injury.

Adult↗

PubMed1990

The ST segment axis as a differential diagnostic feature between acute pericarditis and acute inferior myocardial infarction.

The ST segment electrical axis in the frontal plane was calculated in 20 patients with an acute inferior myocardial infarction (AIMI) and another 20 patients with the acute phase of pericarditis (AP). The ST segment axis of patients with AIMI ranged from 100 degrees-120 degrees (mean 114 degrees). The ST segment axis of patients with AP ranged from 30 degrees-60 degrees (mean 45 degrees). Thus, the ST segment axis can be used for the differential diagnosis in the early acute phase, especially when there are no other important distinguishing factors between these two conditions.

Acute Disease↗

PubMed2002

A comparison of methods for assessing hypothalamic-pituitary-adrenal (HPA) axis activity in asthma patients treated with inhaled corticosteroids.

Suppression of the hypothalamic-pituitary-adrenal (HPA) axis is an accepted indicator of potential side effects from inhaled corticosteroids. Although cortisol monitoring is frequently used to detect changes in HPA axis activity, the optimal method for identifying the subset of asthma patients on inhaled steroids who experience severe cortisol suppression of potential clinical significance has not been established. The objective of this study was to compare several methods for assessing HPA axis activity in asthma patients taking inhaled corticosteroids. After screening, 153 patients with mild to moderate asthma were randomly assigned to receive inhaled fluticasone propionate (110, 220, 330, or 440 microg bid), flunisolide (500 microg or 1000 microg bid), or one of two control regimens (prednisone or placebo) for 21 days. Salivary (8 a.m.) and urinary (24-h) cortisol determinations were compared against 22-hour area under the serum cortisol concentration-time curve (AUC0-22 h) measured at baseline and on day 21. Comparisons were also made against 8 a.m. serum cortisol. A significant positive correlation was found between AUC0-22 h of serum cortisol and 8 a.m. serum cortisol level (r = 0.5140; p = 0.0001). The AUC0-22 h of serum cortisol was weakly correlated with 24-hour urinary cortisol levels, both corrected (r = 0.4388; p = 0.0001) and uncorrected (r = 0.3511; p = 0.0001) for creatinine excretion. The 8 a.m. salivary cortisol level correlated positively with the 8 a.m. serum cortisol level (r = 0.5460; p = 0.0001). Salivary cortisol was both sensitive and specific for the detection of a 50% decline in AUC0-22 h of serum cortisol. Cortisol reductions of this magnitude have been observed following repeated use of inhaled steroids. Because it is noninvasive, salivary cortisol measurement offers distinct advantages as a screening method for detecting pronounced HPA axis suppression in asthma patients receiving corticosteroid therapy.

Administration, Inhalation↗

PubMed2004

Imidazoline2 (I2) receptor- and alpha2-adrenoceptor-mediated modulation of hypothalamic-pituitary-adrenal axis activity in control and acute restraint stressed rats.

Central noradrenaline regulates the activity of the hypothalamic-pituitary-adrenal (HPA) axis and the neuroendocrine response to stress. alpha2-adrenoceptors and imidazoline2 (I2) receptors modulate the activity of the central noradrenergic system. The present set of experiments investigated the role of alpha2-adrenoceptors and I2 receptors in the regulation of HPA axis activity under basal conditions and during exposure to the acute psychological stress of restraint. Three separate experiments were carried out in which rats were given an i.p. injection of either saline vehicle, the combined alpha2-adrenoceptor antagonist and I2 receptor ligand idazoxan (10 mg/kg), the selective I2 receptor ligand BU224 (2.5 or 10 mg/kg) or the selective alpha2-adrenoceptor antagonist RX821002 (2.5 mg/kg) with or without restraint stress. Drugs were administered immediately prior to restraint of 60 min duration. Blood was sampled pre-injection, 30, 60 and 240 min post-injection and plasma corticosterone was measured by radioimmunoassay. In experiment 1, idazoxan increased plasma corticosterone levels in naive animals and potentiated the corticosterone response to acute restraint stress. In experiment 2, BU224 administration increased plasma corticosterone levels in a dose-related manner in naive rats. The results of experiment 3 indicated that RX821002 also elevated plasma corticosterone levels in naive rats, however, only BU224 potentiated the corticosterone response to restraint stress. These studies suggest that both alpha2-adrenoceptors and I2 receptors play a role in modulating basal HPA axis activity and that I2 receptors may play a more important role than alpha2-adrenoceptors in modulating the HPA axis response to the acute psychological stress of restraint.

Acute Disease↗

PubMed1976

Effects of cloprednol and other corticosteroids on hypothalamic-pituitary-adrenal axis function.

The effects of cloprednol and other corticosteroids on hypothalamic-pituitary-adrenal (HPA) function were studied in healthy subjects after administration of a single oral dose of corticosteroid at 6 a.m. or 6 p.m., and after daily 6 a.m. administration of corticosteroids at various doses for seven days. The degree of HPA suppression was assessed by metyrapone tests (METP), insulin hypoglycaemia tests (IHT) and 6 a.m. fasting plasma cortisol concentrations. Regardless of the corticosteroid tested, 6 p.m. dosing was at least four-fold more suppressive of METP response than 6 a.m. administration. At therapeutically equivalent doses, single doses of triamcinolone and dexamethasone were more suppressive of HPA-axis function than cloprednol, hydrocortisone or prednisolone, After 6 a.m. administration for seven days, 12-5 mg of cloprednol did not impair the cortisol response to IHT or interfere with the METP response. The clinically equivalent dose of prednisolone (25 mg) resulted in slightly greater HPA-axis suppression. All doses of dexamethasone (0-5, 3-75 and 6-0 mg) and of betamethasome (2-0, 4-0 and 6-5 mg) were more suppressive of HPA-axis function than either cloprednol or prednisolone. These results suggest that at equipotent anti-inflammatory doses, cloprednol is slightly less suppressive of HPA-axis function than prednisolone, and both cloprednol and prednisolone are much less suppressive than dexamethasone or betamethasone.

Adolescent↗

PubMed1992

Kinematics of the ankle: a hinge axis model.

We used a mechanical method to locate the axis of rotation of the talocrural joint. A single constant axis of rotation was found just distal to the tips of the malleoli. The paths of light-emitting diodes mounted on a talar pin were recorded with time lapse photography during flexion-extension. These paths were analyzed both in the sagittal plane and in a plane perpendicular to the axis of rotation. Sagittal plane studies were distorted by perspective error. The plane used to analyze joint motion or shape must be the plane of motion. Models of the talocrural joint for gait analysis, reconstructive surgery and prosthetic design should have a single offset axis of rotation.

Ankle Joint↗

PubMed2004

Asymmetry in the condylar long axis and first molar rotation.

Asymmetric growth occurs frequently in the mandibulofacial region, but little attention has been given to asymmetry in the temporomandibular joint. The purpose of this study was to clarify the feature of asymmetry in the condylar long axis and its relation to upper first molar rotation. Records of 148 pre-orthodontic patients were used. The angle of the condylar long axis and that of the molar rotation were both larger on the left side than on the right side. Positive correlations were found between the corresponding bilateral measurements of condylar long axes and also between those of molar rotations, whereas no correlation was found between the condylar long axis and molar rotation. These findings were found in most subgroups classified by dental age, skeletal pattern, bite force balance, or gender. These results suggest that consistent left-right differences in the condylar long axis and first molar rotation are common.

Adolescent↗

PubMed2026

Exerkine dysregulation links visceral adiposity to skeletal muscle impairment in end-stage heart failure with reduced ejection fraction: proteomic evidence for a cardio-adipose-muscle axis.

BACKGROUND: Heart failure with reduced ejection fraction (HFrEF) is associated with profound alterations in body composition, skeletal muscle dysfunction, and impaired exercise capacity. Exerkines representing exercise-responsive signaling molecules released by skeletal muscle, adipose tissue, and other organs may mediate systemic metabolic communication between tissues. However, their role in advanced HFrEF and their relationship with adiposity and skeletal muscle characteristics remain poorly understood. METHODS: We studied 73 patients with end-stage HFrEF and 16 healthy controls. Body composition was assessed using computed tomography, including visceral (VAT), subcutaneous (SAT), and epicardial adipose tissue (EAT), as well as skeletal muscle quantity (psoas muscle index, PMI) and quality (psoas muscle density, PMD). Functional performance was evaluated using handgrip strength (HGT) and the 6-min walk test (6MWT). Circulating exerkines were quantified using the Olink technology. Associations between proteins and clinical variables were assessed using age- and creatinine-adjusted linear models with false discovery rate correction. RESULTS: Among patients with HFrEF, 36% were obese and 38% exhibited central obesity independent of BMI. Muscle strength and muscle quality were strongly associated with functional capacity. VAT correlated with muscle mass but not with muscle quality or performance. Compared with controls, HFrEF patients demonstrated elevated inflammatory and metabolic stress-related exerkines including CXCL8, CCL2, IL-6, TNF, IL-15, GDF15, FGF21, ANGPTL4, CTSB, DCN, and resistin. In contrast, proteins associated with muscle integrity and regenerative signaling (myostatin, BDNF, IL-7, SPARC) were significantly reduced. In HFrEF patients leptin strongly correlated with adiposity measures. Metabolic stress mediators (GDF15, IL-15, FGF21, CTSB) were inversely associated with muscle quality and functional performance, whereas myostatin positively correlated with muscle quality, strength, and exercise capacity. BDNF was inversely associated with frailty. CONCLUSIONS: Advanced HFrEF is characterized by a dysregulated exerkine network linking adiposity, skeletal muscle quality, and functional performance. Four biologically coherent axes were identified: a leptin-driven adiposity axis, a metabolic stress-muscle quality axis, a myostatin-related muscle function axis, and a neurotrophic frailty axis. These findings support the presence of a systemic cardio-adipose-muscle signaling network in end-stage HFrEF and identify candidate molecular mediators of sarcopenia and functional decline.

Humans↗

PubMed1996

Clinical and magnetic resonance imaging correlates of hypothalamic-pituitary-adrenal axis function in depression and Alzheimer's disease.

BACKGROUND: An age-related dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is well recognised in animals, but still remains controversial in humans. There is increasing interest that raised corticosteroid levels, due to activation of the HPA axis, may cause both depressive symptoms and cognitive impairments. Steroid effects on cognition may be via the hippocampus, a major site of corticosteroid action and an important structure involved in learning and memory. METHOD: To investigate this further, we examined the relationship between the dexamethasone suppression test, cognitive function, depressive symptoms and hippocampal atrophy on magnetic resonance imaging (MRI) in 32 normal controls, 49 subjects with NINCDS/ADRDA Alzheimer's disease and 51 patients with DSM-III-R Major Depression. RESULTS: Controlling for differences in dexamethasone concentrations, post-dexamethasone cortisol levels were related to advancing age in controls and depressed subjects. However, among subjects with Alzheimer's disease, post-dexamethasone cortisol levels were independently associated with both minor depressive symptoms and hippocampal atrophy on MRI. CONCLUSION: An association between advancing age and increased HPA axis dysregulation is supported for controls and depressed subjects. In Alzheimer's disease, HPA axis changes were associated with depressive symptoms and hippocampal atrophy. Longitudinal studies are now needed to determine the causal direction of these associations.

Aged↗

PubMed1999

Axis I comorbidity in bipolar disorder with psychotic features.

BACKGROUND: Axis I comorbidities are prevalent among patients with severe bipolar disorder but the clinical and psychopathological implications are not clear. AIMS: To investigate characteristics of four groups of patients categorised as follows: substance abuse only (group 1), substance abuse associated with other Axis I disorders (group 2), non-substance-abuse Axis I comorbidity (group 3), no psychiatric comorbidity (group 4). METHOD: Consecutive patients with bipolar disorder with psychotic features (n = 125) were assessed using the Structured Clinical Interview for DSM-III-R--patient version, and several psychopathological scales. RESULTS: By comparison with group 4, group 1 had a higher risk of having mood-incongruent delusions, group 2 had an earlier age at onset of mood disorder, a more frequent onset with a mixed state and a higher risk of suicide, and group 3 had more severe anxiety and a better awareness of illness. CONCLUSIONS: Substance abuse, non-substance-abuse Axis I comorbidity and their reciprocal association are associated with different characteristics of bipolar disorder.

Adult↗

PubMed2005

Effects of 9-cis-retinoic acid on the insulin-like growth factor axis in former smokers.

PURPOSE: Insulin-like growth factor (IGF) axis has been associated with the risk of lung cancer. 9-cis-retinoic acid (9-cis-RA) has shown potential chemopreventive activities in former smokers. This study was designed to evaluate the effects of 9-cis-RA on IGF axis in former smokers to identify any benefit the retinoid may have in preventing lung cancer. PATIENTS AND METHODS: Serum concentrations of IGF-I, IGF binding protein (IGFBP)-3, and their molar ratio (IGF-I/IGFBP-3) were measured with radioimmunoassay kits in stored blood samples from the participants of an original chemoprevention trial. The participants had ceased smoking for at least 12 months and were randomly assigned to receive 3 months of daily oral 9-cis-RA (100 mg) or placebo. All statistical tests were two-sided. RESULTS: A total of 111 samples from the study's baseline and 84 samples from the 3 months treatment were analyzed. The serum concentrations of IGF-I and IGF-I/IGFBP-3 at baseline were significantly lower in female than in male participants. After 3 months of treatment, the serum level of IGF-I and IGF-I/IGFBP-3 were significantly lower in the 9-cis-RA group than in the placebo group (P = .03 and P < .01, respectively), but the IGFBP-3 level was significantly higher (P = .03). CONCLUSION: 9-cis-RA treatment modulated the IGF axis in former smokers, suggesting that the IGF axis is a potential target for the chemopreventive activities of 9-cis-RA and that the serum concentrations of IGF, IGFBP-3, and IGF-I/IGFBP-3 could serve as surrogate end point biomarkers of 9-cis-RA treatment.

Adult↗

PubMed1989

Functional enteroinsular axis in full-term newborn infants.

The term "enteroinsular axis" refers to the enhancement of insulin release by hormones secreted from the gut. Gastric inhibitory polypeptide (GIP) is one of the major hormones that mediates this function. The purpose of the present study was to examine whether the enteroinsular axis is functional in newborn infants born at term gestation. Between d 2 and d 4 of life, glucose was infused for 2 h intravenously or orogastrically to 44 fullterm newborn infants, of whom 18 were appropriate for gestational age, nine large for gestational age, eight small for gestational age; nine infants were born to diabetic mothers. Glucose was infused at either 8 mg/kg/min intravenously or 16 mg/kg/min orogastrically to achieve similar plasma glucose concentrations. Plasma insulin and GIP concentrations were compared. Plasma GIP concentration increased significantly with enteral glucose administration in all infants but remained unchanged with parenteral glucose infusion. The responses of plasma insulin and the insulin/glucose ratio were significantly greater in infants receiving enterally than parenterally infused glucose. However, when glucose was infused orogastrically at a lower rate (8 mg/kg/min), plasma GIP concentrations rose, but no enhancement of insulin response was detected, suggesting the importance of the role of circulating glucose in the "enteroinsular axis". The infants of diabetic mothers and the large-for-gestational-age infants had more rapid insulin response to orogastrically administered glucose, but their GIP responses were similar to that of normal infants. These findings suggest that, at term gestation, the newborn infants have a "functional" enteroinsular axis in response to glucose, i.e. the rising plasma GIP contributed in part to the enhanced insulin response to enterally infused glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

Enteral Nutrition↗

PubMed2002

Neuropeptide Y1 and Y5 receptors mediate the effects of neuropeptide Y on the hypothalamic-pituitary-thyroid axis.

Neuropeptide Y (NPY) is one of the most important hypothalamic-derived neuropeptides mediating the effects of leptin on energy homeostasis. Central administration of NPY not only markedly stimulates food intake, but simultaneously inhibits the hypothalamic-pituitary-thyroid axis (HPT axis), replicating the central hypothyroid state associated with fasting. To identify the specific NPY receptor subtypes involved in the action of NPY on the HPT axis, we studied the effects of the highly selective Y1 ([Phe7,Pro34]pNPY) and Y5 ([chicken pancreatic polypeptide(1-7), NPY(19-23), Ala31, Aib32 (aminoisobutyric acid), Q34]human pancreatic polypeptide) receptor agonists on circulating thyroid hormone levels and proTRH mRNA in hypophysiotropic neurons of the hypothalamic paraventricular nucleus. The peptides were administered continuously by osmotic minipump into the cerebrospinal fluid (CSF) over 3 d in ad libitum-fed animals and animals pair-fed to artificial CSF (aCSF)-infused controls. Both Y1 and Y5 receptor agonists nearly doubled food intake compared with that of control animals receiving aCSF, similar to the effect observed for NPY. NPY, Y1, and Y5 receptor agonist administration suppressed circulating levels of thyroid hormones (T3 and T4) and resulted in inappropriately normal or low TSH levels. These alterations were also associated with significant suppression of proTRH mRNA in the paraventricular nucleus, particularly in the Y1 receptor agonist-infused group [aCSF, NPY, Y1, and Y5 (density units +/- SEM), 97.2 +/- 8.6, 39.6 +/- 8.4, 19.9 +/- 1.9, and 44.6 +/- 8.4]. No significant differences in thyroid hormone levels, TSH, or proTRH mRNA were observed between the agonist-infused FSanimals eating ad libitum and the agonist-infused animals pair-fed with vehicle-treated controls. These data confirm the importance of both Y1 and Y5 receptors in the NPY-mediated increase in food consumption and demonstrate that both Y1 and Y5 receptors can mediate the inhibitory effects of NPY on the HPT axis.

Adipose Tissue↗

PubMed2003

No stress response of the hypothalamo-pituitary-adrenal axis in parturient rats: lack of involvement of brain oxytocin.

During parturition, the basal activity of the hypothalamo-pituitary-adrenal (HPA) axis of Wistar rats is strongly attenuated, whereas the oxytocin system is activated. We investigated the secretory responses of the HPA axis and oxytocin to exposure to a mild emotional stressor (airpuff) comparing virgin female, d 22 pregnant, and parturient rats. Furthermore, as the brain oxytocin system is activated in parturition and oxytocin has been shown to inhibit HPA axis responses in virgin rats, the role of brain oxytocin in the regulation of stress responses during parturition was investigated by intracerebroventricular administration of an oxytocin receptor antagonist before stressor exposure (0.75 micro g/5 micro l). In virgin female rats, exposure to airpuff increased ACTH (2.5 +/- 0.34-fold) and corticosterone (5.1 +/- 2.3-fold) secretion, but in late pregnancy and parturition, the stress-induced increase in ACTH (pregnancy: 1.9 +/- 0.41-fold; parturition: 1.3 +/- 0.13-fold) and corticosterone secretion (parturition: 1.8 +/- 0.40-fold) were strongly attenuated. Oxytocin secretion remained unchanged in response to airpuff in both virgin and parturient rats despite higher overall plasma concentrations in the latter. Oxytocin receptor blockade in the brain elevated basal and stress-induced ACTH secretion in virgin but not pregnant or parturient rats and had no effect on oxytocin secretion either in virgin or parturient rats. We conclude that the reactivity of the HPA axis to external stressors is strongly attenuated during parturition, and this cannot be disinhibited by blocking the receptor-mediated action of brain oxytocin.

Adrenocorticotropic Hormone↗

PubMed2004

Cocaine- and amphetamine-regulated transcript activates the hypothalamic-pituitary-adrenal axis through a corticotropin-releasing factor receptor-dependent mechanism.

Cocaine- and amphetamine-regulated transcript (CART) is a highly expressed hypothalamic transcript that is concentrated in areas associated with the stress response. There is evidence for a role of CART in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis. However, it is not clear whether CART regulates activity of the HPA axis by directly stimulating ACTH release from pituitary corticotropes or through interaction with hypothalamic factors. To address this issue, the effects of central and peripheral administration of CART on the HPA axis were compared. Central administration of CART(55-102) (1 microg) significantly increased circulating levels of ACTH (481 +/- 122 vs. 93 +/- 14 pg/ml; CART vs. vehicle) and corticosterone (460 +/- 29 vs. 179 +/- 62 ng/ml; CART vs. vehicle). In contrast, iv injection of CART(55-102) (0.09-9.0 nmol/kg) did not significantly affect circulating levels of ACTH or corticosterone. The corticotropin-releasing factor (CRF) receptor antagonist Astressin B was used to determine whether CART(55-102) elicits ACTH secretion via a CRF receptor-dependent mechanism. Injection of Astressin B (50 microg/kg, iv) inhibited CART(55-102)-induced ACTH and corticosterone responses. The effects of CART(55-102) on CRF and arginine vasopressin (AVP) expression were also examined in static hypothalamic explants. RT-PCR analysis revealed a significant up-regulation of CRF and AVP mRNA levels after CART(55-102) (10 nm and 1 microm) treatment. Last, the effects of CART(55-102) on CRF- and AVP-mediated ACTH release was investigated in dispersed rat anterior pituitary cells. Incubation of CART(55-102) (10-100 nm) did not significantly affect ACTH release from anterior pituitary cells. Findings from the present study suggest that CART regulates activity of the HPA axis through a CRF-dependent central mechanism and not by means of direct interaction with pituitary corticotropes.

Adrenocorticotropic Hormone↗

PubMed2005

Steroid receptor coactivator-1-deficient mice exhibit altered hypothalamic-pituitary-adrenal axis function.

Steroidogenic factor-1 (SF-1), has emerged as a critical nuclear receptor regulating development and differentiation at several levels of the hypothalamic-pituitary-steroidogenic axis. Although many coregulatory factors have been shown to physically and functionally interact with SF-1, the relative importance of these interactions in SF-1 target tissues has not been thoroughly established. In this study we assessed roles of steroid receptor coactivator-1 (SRC-1) in hypothalamic-pituitary-adrenal (HPA) axis function using SRC-1-deficient (SRC-1-/-) mice in the absence or presence of SF-1 haploinsufficiency. Surprisingly, SRC-1 deficiency did not alter baseline HPA axis function or the acute rise in corticosterone after ACTH administration and failed to exacerbate adrenocortical dysfunction in SF-1+/- mice. However, after exposure to paradigms of acute and chronic stress, SRC-1-/- mice exhibited an elevation in serum corticosterone despite normal (nonsuppressed) ACTH, suggesting an increase in adrenal sensitivity as well as a concomitant defect in glucocorticoid-mediated feedback inhibition of the HPA axis. An examination of potential compensatory mechanism(s) revealed an increase in adrenal weight, selective elevation of melanocortin 2 receptor mRNA, and a coincident increase in SRC-2 and SRC-3 expression in SRC-1-/- adrenals. A reduction in blood glucose was observed in SRC-1-/- mice after chronic stress, consistent with a generalized state of glucocorticoid resistance. Dexamethasone suppression tests confirmed a weakened ability of glucocorticoids to 1) elevate serum glucose levels and induce hepatic phosphoenolpyruvate carboxykinase transcription and 2) suppress pituitary proopiomelanocortin transcript levels in SRC-1-/- animals. Collectively, these data are consistent with an indispensable role for SRC-1 in mediating actions of glucocorticoids in pituitary and liver.

Adrenal Glands↗