PHYSIOLOGY AND PATHOPHYSIOLOGY OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS
下丘脑-垂体-肾上腺轴的生理学和病理生理学
基本信息
- 批准号:3878083
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:
- 资助国家:美国
- 起止时间:至
- 项目状态:未结题
- 来源:
- 关键词:Cushing's syndrome adolescence (12-20) adrenal disorder adrenal hyperplasia anorexia anorexia nervosa chronic fatigue syndrome clinical depression corticosteroid receptors corticotropin releasing factor cortisone endocrine disorder diagnosis endocrine pharmacology genetic regulation glucocorticoids hormone metabolism hormone receptor hormone regulation /control mechanism human subject human tissue hypothalamus neurotransmitter metabolism neurotransmitters nutrition related tag organ culture pituitary adrenal axis pituitary disorders point mutation pregnancy sheep stress stress proteins
项目摘要
In this project we seek to advance the understanding of the physiology and
pathophysiology of the hypothalamic-pituitary-adrenal axis. The role of
stress-related hormones in normal and disease states is being examined, and
clinical applications for these hormones are sought. The recent discovery
of the structure of corticotropin releasing hormone (CRH) and the
development of sensitive assays for measuring stress-related hormones and
their receptors have led to rapid progress in this field. Major progress
has been made in three areas:
1) Clinical applications of CRH: An ovine CRH (oCRH) stimulation test has
been developed that is useful in the differential diagnosis of adrenal
insufficiency. Cushing's syndrome and pseudo-Cushing's states (psychiatric
hypercortisolism). The human CRH (hCRH) analog is useful in studying the
physiology of the pituitary-adrenal axis. The oCRH stimulation test and
measurement of CSF CRH have increased our understanding of the
pathophysiology of Cushing's syndrome, melancholic depression, atypical
depression, seasonal depression, the premenstrual tension syndrome,
anorexia nervosa the chronic fatigue syndrome and late-onset congenital
adrenal hyperplasia.
2) The regulation of the axis by opioids, vasopressin, oxytocin,
glucocorticoids, platelet activating factor (PAF), tumor necrosis factor -
alpha, cholecystokinin (CCK), neuropeptide Y, benzodiazepine agonists and
antagonists and thyroid hormones has been studied in vivo and/or in vitro.
Neurotransmitter and feedback regulation of hypothalamic CRH secretion has
also been examined in vitro. Third trimester pregnant women and athletes
have a hyperfunctional pituitary-adrenal axis in the resting state.
Hypothalamic-pituitary-adrenal axis reactivity and personality traits have
been correlated in developing adolescents. The hCRH gene 5' regulatory
region has been cloned sequenced and its regulation is being studied.
3) Role and actions of glucocorticoids: The effects of glucocorticoids upon
the cardiovascular system during surgical stress are merely permissive.
Surgical Stress is associated with continuous and pulsatile secretion of
ACTH. Glucocorticoid resistance is an autosomal recessive disease
associated with normal size glucocorticoid receptor protein that has
decreased affinity for glucocorticoids and normal size mRNA. We have found
a nonconserved point mutation (Asp --> Val) in the steroid binding domain
of the glucocorticoid receptor which leads to a decrease in the affinity of
the receptor for glucocorticoids and decreased glucocorticoid effect. The
interaction of the glucocorticoid receptor with the heat-shock proteins is
studied.
在这个项目中,我们试图推进对生理学和
项目成果
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{{ truncateString('G P CHROUSOS', 18)}}的其他基金
PHYSIOLOGY AND PATHOPHYSIOLOGY OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS
下丘脑-垂体-肾上腺轴的生理学和病理生理学
- 批准号:
6108012 - 财政年份:
- 资助金额:
-- - 项目类别:
PHYSIOLOGY OF STRESS AND CLINICAL APPLICATIONS OF CORTICOTROPIN RELEASING HORMONE
应激生理学和促肾上腺皮质激素释放激素的临床应用
- 批准号:
4693770 - 财政年份:
- 资助金额:
-- - 项目类别:
PHYSIOLOGY AND PATHOPHYSIOLOGY OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS
下丘脑-垂体-肾上腺轴的生理学和病理生理学
- 批准号:
3942055 - 财政年份:
- 资助金额:
-- - 项目类别:
Pathophysiology of the Hypothalamic-pituitary-adrenal &
下丘脑-垂体-肾上腺的病理生理学
- 批准号:
6541135 - 财政年份:
- 资助金额:
-- - 项目类别: