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HPA Axis Activity (hpa axis + activity)
Selected AbstractsHypothalamic,pituitary,adrenal axis activity and early onset of cannabis useADDICTION, Issue 11 2006Anja C. Huizink ABSTRACT Aims To identify early onset cannabis users by measuring basal hypothalamic,pituitary,adrenal (HPA) axis activity, which may be a risk factor for early onset substance use when showing low activity. Design In a prospective cohort study, adolescents who initiated cannabis use at an early age (9,12 years), those who initiated at a later age (13,14 years) and those who did not use cannabis by the age of 14 were compared with respect to HPA axis activity. Setting and participants Data were used from the first and second assessment wave of the TRacking Adolescents' Individual Lives Survey (TRAILS), that included 1768 Dutch young adolescents aged 10,12 years who were followed-up across a period of 2 years. Measurements Cortisol was measured in saliva samples at awakening, 30 minutes later and at 8 p.m. at age 10,12. Self-reported age at first cannabis use was used. Findings The early onset group had lower cortisol levels 30 minutes after awakening than the late onset group (OR = 0.93, 95% CI: 0.86,0.99). Furthermore, compared to non-users, the early and late onset cannabis users had higher levels of cortisol at 8 p.m. (OR = 1.25, 95% CI: 1.03,1.53 and OR = 1.21, 95% CI: 1.01,1.45, respectively). Conclusions Some evidence was found for HPA axis hypo-activity at awakening in adolescents with early onset of cannabis use compared to late onset users, which might indicate an increased risk for early onset users of seeking stimulation to restore arousal levels by using substances. [source] Immediate,early gene induction in hippocampus and cortex as a result of novel experience is not directly related to the stressfulness of that experienceEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2005Thaddeus W. W. Pace Abstract The stressful quality of an experience, as perceived by rats, is believed to be largely represented by the magnitude of a hypothalamic,pituitary,adrenal (HPA) axis response. The hippocampus may be especially important for assessing the stressfulness of psychological stressors such as novel experience. If such is the case then experience-dependent immediate,early gene expression levels within the hippocampus may parallel relative levels of HPA axis activity. We examined this prospect in rats that were placed in four different novel environments (empty housing tub, circular arena, elevated pedestal or restraint tube). Restraint and pedestal produced the largest magnitude of increased ACTH and corticosterone secretion, arena an intermediate level (Experiment 2) and tub the least magnitude of increase. We saw a very similar experience-dependent pattern of relative Fos protein, c-fos mRNA and zif268 mRNA expression in the paraventricular nucleus of the hypothalamus. However, in hippocampus (and select regions of cortex), immediate,early gene expression was associated with the exploratory potential of the novel experience rather than level of HPA axis activity; pedestal and arena elicited the greatest immediate,early gene expression, tub an intermediate level and restraint the least amount of expression. We conclude that the stressfulness of psychological stressors is not represented by the amount of immediate,early gene induction elicited in hippocampus and cortex, nor does there appear to be a general enhancing or depressive influence of acute stress on immediate,early gene induction in those brain regions. [source] The CRHR1 gene: a marker for suicidality in depressed males exposed to low stressGENES, BRAIN AND BEHAVIOR, Issue 1 2008D. Wasserman The risk of suicide, which causes about 1 million deaths each year, is considered to augment as the levels of stress increases. Dysregulation in the stress response of the hypothalamic-pituitary-adrenocortical (HPA) axis, involving the corticotrophin-releasing hormone (CRH) and its main receptor (CRHR1), is associated with depression, frequent among suicidal males. Here we have analyzed single nucleotide polymorphisms (SNPs) in these genes, in family trios with suicide attempter offspring (n = 542), by using the transmission disequilibrium test both in a two-staged screening/replication sample design and in detailed reanalysis in the entire sample. Stratification based on the levels of lifetime stress showed reproducible association and linkage of an SNP in the CRHR1 gene (rs4792887) to suicide attempters exposed to low levels of stress (P = 0.002), among whom most males were depressed (P = 0.001). The identified allele may represent a part of the genetic susceptibility for suicidality by increasing HPA axis activity upon exposure to low levels of stress. [source] Fetal programming and fetal psychologyINFANT AND CHILD DEVELOPMENT, Issue 1 2010Peter T. Ellison Abstract The introduction of the ,fetal programming hypothesis', first in epidemiology, subsequently in a broad range of disciplines concerned with developmental biology, has generated new interest in phenotypic plasticity, the mechanisms that govern it, and its place in evolutionary biology. A number of epidemiological studies link small size at birth, assumed to be a consequence of constrained prenatal energy availability, with adverse effects on the risk of chronic diseases later in life. The cluster of chronic diseases associated with the metabolic syndrome and alterations of glucose metabolism are particularly implicated. Recent evidence suggests that epigenetic modification of gene expression affecting the hypothalamic-pituitary-adrenal (HPA) axis may be involved in these effects. In animal studies epigenetic alteration of HPA axis activity and responsiveness is associated with changes in adult behaviour and stress responsiveness. The potential for similar effects to contribute to psychological and psychiatric outcomes in humans has been explored in a number of contexts, including famine exposure, observed covariance with birth weight, and prenatal dexamethasone treatment of fetuses at risk of congenital adrenal hyperplasia. While fetal programming effects have now been widely demonstrated across species and human populations, the adaptive significance of these effects is still a matter of debate. Copyright © 2010 John Wiley & Sons, Ltd. [source] Hypothalamic-Pituitary-Adrenal Axis Abnormalities in Response to Deletion of 11,-HSD1 is Strain-DependentJOURNAL OF NEUROENDOCRINOLOGY, Issue 11 2009R. N. Carter Inter-individual differences in hypothalamic-pituitary-adrenal (HPA) axis activity underlie differential vulnerability to neuropsychiatric and metabolic disorders, although the basis of this variation is poorly understood. 11,-Hydroxysteroid dehydrogenase type 1 (11,-HSD1) has previously been shown to influence HPA axis activity. 129/MF1 mice null for 11,-HSD1 (129/MF1 HSD1,/,) have greatly increased adrenal gland size and altered HPA activity, consistent with reduced glucocorticoid negative feedback. On this background, concentrations of plasma corticosterone and adrenocorticotrophic hormone (ACTH) were elevated in unstressed mice, and showed a delayed return to baseline after stress in HSD1-null mice with reduced sensitivity to exogenous glucocorticoid feedback compared to same-background genetic controls. In the present study, we report that the genetic background can dramatically alter this pattern. By contrast to HSD1,/, mice on a 129/MF1 background, HSD1,/, mice congenic on a C57Bl/6J background have normal basal plasma corticosterone and ACTH concentrations and exhibit normal return to baseline of plasma corticosterone and ACTH concentrations after stress. Furthermore, in contrast to 129/MF1 HSD1,/, mice, C57Bl/6J HSD1,/, mice have increased glucocorticoid receptor expression in areas of the brain involved in glucocorticoid negative feedback (hippocampus and paraventricular nucleus), suggesting this may be a compensatory response to normalise feedback control of the HPA axis. In support of this hypothesis, C57Bl/6J HSD1,/, mice show increased sensitivity to dexamethasone-mediated suppression of peak corticosterone. Thus, although 11,-HSD1 appears to contribute to regulation of the HPA axis, the genetic background is crucial in governing the response to (and hence the consequences of) its loss. Similar variations in plasticity may underpin inter-individual differences in vulnerability to disorders associated with HPA axis dysregulation. They also indicate that 11,-HSD1 inhibition does not inevitably activate the HPA axis. [source] Blunted Pituitary-Adrenocortical Stress Response in Adult Rats Following Neonatal Dexamethasone TreatmentJOURNAL OF NEUROENDOCRINOLOGY, Issue 10 2000K. Felszeghy Abstract Glucocorticoids have a prominent impact on the maturation of the stress-related neuroendocrine system and on the postnatal establishment of adaptive behaviour. The present study aimed at investigating the stress responsiveness of the hypothalamo-pituitary-adrenocortical (HPA) axis in young and adult rats after neonatal treatment with the synthetic glucocorticoid agonist, dexamethasone. Newborn male Wistar rats were injected s.c. with 1 µg/g dexamethasone on postnatal days 1, 3 and 5. Circulating adrenocorticotropic hormone (ACTH) and corticosterone concentrations were measured in the resting state and following a 30-min cold stress at the age of 10 days, as well as after a 30-min restraint stress at the age of 14 weeks. Also in adults, pituitary and adrenocortical hormone responsiveness was evaluated after i.v. administration of 2 µg/kg corticotropin releasing hormone (CRH). In addition, glucocorticoid (GR) and mineralocorticoid receptor (MR) binding capacities were assessed in the pituitaries of adult rats. The results showed that at day 10 basal ACTH concentration was elevated while the cold stress-evoked ACTH response was attenuated in the dexamethasone-treated rats. As adults, treated rats showed a suppressed elevation of both ACTH and corticosterone plasma cncentrations in response to restraint, while basal hormonal concentrations were not altered. There was no difference in the magnitude of the CRH-induced elevation of ACTH and corticosterone concentrations initially; however, the dexamethasone-treated animals showed a prolonged secretion of both hormones. These animals also showed a selective decrease in pituitary GR binding capacity. Neonatal dexamethasone treatment strongly suppressed body weight gain, and adrenal and thymus weights in the early phase of postnatal development. By adulthood, the body and adrenal weights were normalized while thymus weight was greater than in controls. These findings indicate that neonatal dexamethasone treatment permanently alters HPA axis activity by reducing stress responses to cold and restraint probably through supra-pituitary actions, and by decreasing the effectiveness of feedback through a diminished GR binding in the pituitary. [source] Prenatal synthetic glucocorticoid exposure alters hypothalamic,pituitary,adrenal regulation and pregnancy outcomes in mature female guinea pigsTHE JOURNAL OF PHYSIOLOGY, Issue 5 2010Elizabeth Dunn Preterm delivery occurs in approximately 10% of all pregnancies. Prenatal exposure to synthetic glucocorticoids (sGCs) reduces the incidence of respiratory distress syndrome (RDS) in these babies. Therefore, administration of multiple courses of sGCs became common practice. Animal and human studies have demonstrated that multiple courses of sGCs can have long-term effects. While the majority of animal studies have been undertaken in male offspring, it is emerging that there are profound sex differences in the consequences of prenatal sGC exposure. To our knowledge, no studies have determined the effects of prenatal sGC exposure on hypothalamic,pituitary,adrenal (HPA) axis function in female offspring while accounting for reproductive cycle status, or determined if there are effects on pregnancy parameters. Pregnant guinea pigs were administered three courses of betamethasone (Beta), dexamethasone (Dex) or vehicle on gestational days 40/41, 50/51 and 60/61. In adulthood (age range: postnatal days 126,165), basal and activated HPA axis function were assessed at various stages of the reproductive cycle. The female offspring were then mated and underwent an undisturbed pregnancy. Females were killed in the luteal phase of the reproductive cycle following litter weaning, and molecular analysis undertaken. In the luteal phase, Beta-exposed females exhibited significantly lower basal salivary cortisol levels (P < 0.05). Dex-exposed females also exhibited significantly lower basal salivary cortisol levels during the luteal phase (P < 0.05), but increased basal salivary cortisol levels during the ostrous phase (P < 0.01). The Beta-exposed females exhibited increased glucocorticoid receptor (GR) mRNA expression in the CA1/2 region of the hippocampus (P < 0.05) and MC2R mRNA in the adrenal cortex (P < 0.05). The Dex-exposed animals exhibited higher hippocampal GR and mineralocorticoid receptor (MR) mRNA levels (P < 0.05). Beta-exposed females showed reduced fecundity (P < 0.05). In Dex-exposed females there was a lower male to female sex ratio. In conclusion, prenatal sGC exposure affects HPA axis activity, in a cycle-dependent manner, and long-term reproductive success. The clinical implications of the findings on endocrine function and pregnancy in females are profound and further follow-up is warranted in human cohorts. Furthermore, we have shown there are considerable difference in phenotypes between the Beta- and Dex-exposed females and the specific endocrine and maternal outcome is contingent on the specific sGCs administered during pregnancy. [source] | |||||||||||||