ISSN:1068-3097    

出版商:OVID    

年代:1998

数据来源: OVID

ISSN:1068-3097    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Cortisol has a number of surprising abilities. Perhaps the most interesting of these is its ability to bind to the mineralocorticoid receptor with an affinity equivalent to that of aldosterone. In sodium-transporting epithelia, 11β-hydroxysteroid dehydrogenase type 2(11βHSD2) converts cortisol to the receptor-inactive cortisone, allowing aldosterone to bind to its receptor in the setting of much higher circulating levels of glucocorticoid. Mutations in 11βHSD2 account for the congenital syndrome of apparent mineralocorticoid excess (AME), a low-renin, life-threatening form of hypertension resulting from overstimulation of the mineralocorticoid receptor by cortisol in the distal tubule of the kidney. The receptor and enzyme also colocalize in the gut, the sweat glands, and the lung. There is increasing evidence that the actions of 11βHSD2 also play an important role in other physiologic processes, notably reproduction. In the placenta, 11βHSD2 protects the fetus from high levels of maternal glucocorticoids; in other tissues, high localized levels of the enzyme lower the intracellular levels of glucocorticoids in specialized cells such as the nonluteinized granulosa cells of the human ovary and the epithelial cells of the endometrium, suggesting that fertility may also be affected in patients with AME. The extent to which these tissues are affected will be determined, inter alia, by the presence of other yet undiscovered oxidative isoforms of 11β-hydroxysteroid dehydrogenase.

ISSN:1068-3097    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Congenital lipoid adrenal hyperplasia (lipoid CAH) is the most severe of the CAH syndromes, eliminating virtually all adrenal and gonadal steroid hormone synthesis. Previously regarded as a rare, esoteric condition, lipoid CAH has recently received considerable attention since the discovery that lipoid CAH was caused by mutations in the gene for the steroidogenic acute regulatory protein (StAR), and the demonstration that the disease is fairly common in Japan. Clinical studies of lipoid CAH substantially illuminated the biology of the StAR protein, as lipoid CAH constitutes a StAR gene knockout experiment of nature. Studies of lipoid CAH showed that steroidogenic cells employ both StAR-dependent and StAR-independent modes of steroidogenesis. This in turn indicated that the lipoid CAH phenotype was due to two events: first, a loss of StAR-dependent steroidogenesis led to diminished steroidogenesis and to cellular accumulation of cholesterol esters; second, cellular damage caused by this accumulation eliminated StAR-independent steroidogenesis. This two-hit model of lipoid CAH explains the variable onset of salt loss and the presence of apparently normal pubertal feminization in affected 46,XX females. However, the mechanism of StAR's action to promote the flow of cholesterol into mitochondria remains unknown.

ISSN:1068-3097    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

There is little direct evidence from viral culture for HIV infection in the adrenal glands, but infiltration of endocrine tissues by opportunistic infection or malignancy is common. Loss of adrenocortical function can be difficult to assess, particularly when medications used in the treatment of opportunistic infections result in hormonal or metabolic disturbances. In most cases basal cortisol levels indicate that adrenal function is normal for desperately ill patients. Standard provocative tests, however, may reveal subtle abnormalities of adrenal and pituitary hormone production. Changes in adrenal steroidogenesis do occur, with the result that cortisol production is favored over adrenal androgen and miner-alocorticoid production. Adrenal reserve can be limited. An acquired glucocorticoid resistance may explain high cortisol levels in some cases. Complex interactions between the endocrine and immune systems may influence the progression of HIV infection to AIDS. Further research is necessary to clarify these interactions.

ISSN:1068-3097    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

In clinical practice we measure cortisol in plasma and urine and treat disorders of cortisol secretion. In research, extensive studies have dissected the factors that influence the hypothalamic-pituitary-adrenal axis and modulate cortisol secretion. In recent years, however, the research focus has turned toward factors influencing tissue sensitivity to cortisol, both in sites responsible for negative feedback and in peripheral tissues. Key observations include the cloning of glucocorticoid and mineralocorticoid receptors, dissection of their signaling pathways, and recognition of the importance of cortisol metabolism in modulating tissue sensitivity. This article reviews recent data that illustrate the extent to which these research findings are now being applied in clinical practice, addresses the question of whether intrinsic sensitivity to glucocorticoids varies between individuals, and emphasizes the important impact on health and on responsiveness to glucocorticoid therapy.

ISSN:1068-3097    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Aldosterone is an important regulator of fluid and electrolyte balance. The capacity of the adrenal gland to produce aldosterone is controlled by circulating levels of angiotensin II and potassium, which regulate the expression of aldosterone synthase (CYP11B2). This enzyme catalyzes the final steps of aldosterone synthesis and is expressed only in the zona glomerulosa of the adrenal cortex. The development of new systems for in vitro studies of expression has helped to define the molecular mechanisms that regulate this enzyme and thus the capacity of the adrenal gland to produce aldosterone. Both potassium and angiotensin II increase intracellular calcium levels, which regulate expression of CYP11B2 through transcription factors that interact with defined sites in the 5-flanking region of the gene.

ISSN:1068-3097    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Since the first cloning of members of the nuclear receptor superfamily, it has become evident that different isoforms are generated from single genes by various mechanisms such as utilization of alternative promoters, alternative splicing, and use of different translation initiation or polyadenylation sites. Different mineralocorticoid receptor mRNA isoforms have been identified in human and rat, which are submitted to tissue-specific expression and regulation. Recent studies indicate the existence of receptor variants with putative different functional properties, which could account for differences in target cell responsiveness to hormones. We review molecular mechanisms involved in generation of mRNA or protein isoforms and discuss the potential physiopathologic implications of mineralocorticoid receptor variants.

ISSN:1068-3097    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Therapy for adrenocortical carcinoma remains frustratingly problematic, and the prognosis for affected patients is dismal. Recent attempts to better understand the biology of these tumors have unraveled a number of abnormalities. Some features appear merely to reflect the growth potential of these tumors and loss of differentiated functions, whereas others may play a pathogenetic role. Particularly interesting is the frequent genetic turmoil at the 11 p15 locus, resulting in loss of the maternal allele and duplication of the paternal allele. This chromosomal region bears imprinted genes that are probably involved in the fine tuning of adrenocortical cell proliferation: antioncogenes (eg,p57K/P2and H19) and growth factors (eg, insulinlike growth factor-ll). These studies have revealed new molecular markers of the malignant phenotype that markedly improve the diagnosis of and prognosis for adrenocortical carcinoma. Genotyping of adrenocortical tumors will probably become more widely used and even obligatory for selecting patients for participation in trials of adjuvant chemotherapy after apparent curative surgery.

ISSN:1068-3097    

出版商:OVID    

年代:1998

数据来源: OVID

ISSN:1068-3097    

出版商:OVID    

年代:1998

数据来源: OVID