ISSN:1068-3097    

出版商:OVID    

年代:2001

数据来源: OVID

ISSN:1068-3097    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

The presence of specific cell surface receptors for adrenocorticotropic hormone (ACTH) was first demonstrated in 1970. However, characterization and localization of the ACTH binding site have been extensively studied in adrenal cells of different species only in the 1980s. Cloning of the human ACTH and &agr;-MSH receptors in 1992 defined a new class of G protein coupled receptors: the melanocortin receptor family, which comprises five members named MC1-R to MC5-R where MC2-R is the ACTH receptor. Thereafter, characterization of the promoter ofMC2-Rgene revealed that the orphan nuclear receptor steroidogenic factor 1 (SF-1) is involved in the regulation of its activity like some other genes of the steroidogenic pathway. Several inactivating mutations in the MC2-R gene are responsible for the ACTH resistance found in the familial isolated glucocorticoid deficiency syndrome or FGD.

ISSN:1068-3097    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Classically, aldosterone activates mineralocorticoid receptors, which then act as ligand-dependent transcriptional regulators of target genes. The mechanism of action of aldosterone in both epithelial and nonepithelial tissues is not well understood. This review summarizes recent studies on a number of candidate mineralocorticoid target genes that are activated within hours after physiologic levels of aldosterone are reached. These include the genes for the subunits of the epithelial sodium channel and Na+K+ATPase pump and genes coding for three proteins (a serine/threonine kinaseSGK1; a small guanosine triphosphate (GTP)-binding proteinK-Ras2A; and channel-inducing factor orCHIF) that regulate Na+channel activity in epithelia. The authors discuss evidence for induction by aldosterone of the angiotensin IIAT1receptor gene in the heart, which may contribute to the fibrotic response of the heart to elevated aldosterone and salt.

ISSN:1068-3097    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

With improved screening and the recognition of normokalemic variants, it has become clear that primary hyperaldosteronism is the most common cause of secondary hypertension. Primary hyperaldosteronism is characterized by an excessive production of aldosterone that is not driven by known stimulators of aldosterone secretion, although these may retain some degree of modulatory activity. The ratio of plasma aldosterone to plasma renin activity is a reliable screening method for this syndrome. Confirmation of the diagnosis requires demonstration that aldosterone secretion is not suppressed by volume expansion or sodium loading. Several subtypes of primary hyperaldosteronism with different pathophysiologic characteristics and responses to surgery have been recognized, the most common being unilateral aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA) caused by bilateral zona glomerulosa hyperplasia. The purpose of this review is to address the new understanding of prevalence, subtype characteristics, and methods of screening and diagnosis.

ISSN:1068-3097    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Dehydroepiandrosterone (DHEA) and its sulfate ester are the most abundant steroids in human circulation but only recently received the attention of the scientific community. Biosynthesis of DHEA occurs in the adrenal zona reticularis and the gonads and is catalyzed by P450c17. In humans, DHEA is the crucial precursor for all sex steroids and exhibits indirect action after peripheral conversion to androgens and estrogens. In addition, DHEA can exert direct effects via interaction with neurotransmitter receptors in the brain. These two mechanisms of action explain most of the observed clinical effects: androgenic and estrogenic effects on lipids, skin, bone, skin and body composition; and neurosteroidal effects on mood and libido. However, neurosteroidal effects of DHEA replacement are only seen in patients with a pathologic loss of DHEA production (ie,adrenal insufficiency) and patients with impaired well-being and sexuality. Volunteers with normal well-being do not experience further improvements after DHEA administration. Future prospects of DHEA replacement involve its establishment as part of the standard replacement therapy in adrenal insufficiency and the investigation of potential benefits in patients receiving chronic glucocorticoid treatment and in women with androgen deficiency.

ISSN:1068-3097    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

High doses of glucocorticoid have adverse effects on bone, resulting in decreased bone mass and increased risk of fracture. There is substantial intraindividual variation in susceptibility to these effects and the condition is difficult to treat effectively. The mechanisms underlying the adverse effects of glucocorticoids are complex but actions on the bone-forming cell, the osteoblast, appear to be critical. Recent studies have clarified the epidemiology of fracture risk and have improved the understanding of the pathophysiology underlying glucocorticoid-induced osteoporosis. Agents that inhibit bone resorption have proven to be useful treatments and advances have been made toward the development of anabolic therapies. Future areas of research include the continued search for safe, effective anabolic agents and the development of predictive tests to allow more effective targeting of treatments to individuals most at risk of fracture.

ISSN:1068-3097    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Recent key advances in the biology of melatonin have been made in the understanding of the cellular biochemistry underlying the clock mechanism and of the nature of the melatonin receptors. Another recent development is the interest in phototransduction mechanisms and the spectral sensitivity of the effects of melatonin in man. Specific, high-affinity analogues are still required to help clarify the full range of melatonin actions. Melatonin has been found to have a number of other actions besides its contribution to circadian and seasonal rhythms, with research centering on the anticancer effects. This broadens the possible therapetic use to conditions other than those associated with phase shifts and sleep disorders.

ISSN:1068-3097    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Evidence is presented indicating that the initiation of mammalian puberty requires an array of transsynaptic and glial–neuronal interactions, brought about by neurons using excitatory and inhibitory amino acids as transmitters and astroglial cells producing cell–cell signaling molecules able to regulate neuronal function. Although a glutamate-to-GABA hierarchical arrangement appears prominent in the brain, it is still unclear which of these two neurotransmitter systems is primarily responsible for initiating the transsynaptic cascade of events that unleashes the pubertal increase in LHRH release. In contrast, there is now considerable evidence demonstrating that members of the TGF-β and EGF families of trophic factors are key components of the glia-to-neuron communication pathways used by glial cells to facilitate LHRH release. Progress has also been made toward the identification of genes belonging to the hierarchy of upstream molecules that presumably control the initiation of puberty.

ISSN:1068-3097    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Corticotropin-releasing hormone (CRH) is a key regulator of the endocrine, behavioral, autonomic, immune, and metabolic responses to stress. The discovery of urocortin, a mammalian peptide capable of eliciting CRH-like effects, and two CRH-receptors has complicated our understanding of the molecular mechanisms mediating particular aspects of the stress response. Recent studies using genetic, pharmacologic, and anatomic techniques have addressed the specific roles of the individual ligands and receptors of the CRH system in stress. Whereas distinct roles for CRH and other CRH-like ligands remain somewhat ill defined, recent studies dissecting the roles of the individual CRH-receptors have been more successful, suggesting dominant roles for each receptor subtype in particular aspects of the stress response and modulatory roles in others. Finally, clinical application of selective CRH-receptor antagonists has recently shown great therapeutic potential in treating major depression and anxiety disorders.

ISSN:1068-3097    

出版商:OVID    

年代:2001

数据来源: OVID