ISSN:1068-3097    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:1068-3097    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

During the preceding decade, major advances have been made in our understanding of the adrenal steroid hormone biosynthesis. Although the final hydroxylation steps are catalyzed by different cytochromes P450, which have been cloned and characterized in detail, the electron transferring proteins also play a pivotal role in oxygen activation and product formation. Adrenodoxin transfers electrons from adrenodoxin reductase to mitochondrial cytochromes P450. Its role in regulating adrenal steroid production has long been underestimated, and our recent understanding is mainly based onin vitrostudies using bovine adrenodoxin. Although only a few reports on this topic have been published within the past 12 months, recent data have demonstrated that the concentration of adrenodoxin as well as its electron transfer and redox partner interaction properties affect steroid biosynthesis. Thorough investigation of these complex processes in different species offers the hope of improved understanding of adrenal steroid biosynthesis.

ISSN:1068-3097    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Concerns about the sensitivity of the standard synacthen test for assessment of the hypothalamic-pituitary-adrenal (HPA) axis were raised when patients with undoubted HPA axis deficiency “passed” the test. It was postulated that 250 μg of synthetic adrenocorticotrophic hormone (ACTH) overstimulates adrenals and produces falsely adequate cortisol response. A low-dose synacthen test was then advocated. Initial reports of supraphysiologic plasma synthetic ACTH levels after administration of 1 μg have recently been refuted. Studies investigating the low-dose synacthen test reported good reproducibility and higher sensitivity compared with the standard test. Standard 1-μg dilution, harmonization of plasma cortisol assays, uniform sampling time, and plasma cortisol cut-off need to be resolved. The latter is likely to vary between centers; our experience indicates that plasma cortisol levels greater than 600 nmol/L practically exclude HPA axis deficiency; levels less than 400 nmol/L practically confirm HPA axis deficiency; and values between 400 and 600 nmol/L should be interpreted in the light of other clinical data. Evidence supporting its use is accumulating, and the low-dose synacthen test is likely to soon become a first-line screening test for HPA axis assessment.

ISSN:1068-3097    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

The recent advances in molecular endocrinology have resulted in clearer understanding of the process of differentiation and zonation of the mammalian adrenal cortex. Precursors of steroidogenic tissues appear in a rat embryo at an early stage of gestation, cleaving into the adrenal and gonad portions at midgestation. During the late stage of pregnancy, cortical precursor cells in the adrenal primordium become able to produce corticosterone, aligning themselves under the possible influence of developing microvasculature, and the medullary cells establish themselves at the central part of the gland. The completion of the fasciculata zone and the aldosterone-producing glomerulosa zone occur around term.The functionally undifferentiated zone between the zonae glomerulosa and fasciculata of the adult cortex seems to contain cortical stem cells, which migrate into the fasciculata zone after a space of time. The results obtained by the regeneration experiments as well as the transplantation experiments corroborate a notion that cells attached to the adrenal capsule could change their phenotypes under specific physiologic conditions.

ISSN:1068-3097    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Stress is both an evolutionary drive for normal life and a mechanism of disease. An intact cellular crosstalk between the immune and neuroendocrine systems is crucial for stress responses and thus normal development, homeostasis, and coping with the environment. Distortion of this interaction may constitute a primary or secondary event in many disease processes. Cytokines, as the main mediators of the immune cells, can activate the hypothalamic-pituitary-adrenal (HPA) axis at all three levels. They regulate the hormonal output from the adrenal gland in a differential fashion, which in return acts on the immune system. In addition to a systemic, paracrine, or autocrine role of cytokines on the adrenal gland, the inner zone of the adrenal cortex expresses major histocompatibility class II molecules and contains lymphocytes in direct cellular contact with steroid-producing cells. Lymphocytes activate androgen-producing cells in a cytokine-independent manner, suggesting direct cell-cell mediated mechanisms of immune-endocrine interaction. Adrenocorticotropic hormone (ACTH)–independent immune-adrenal interactions have been shown to be involved in the maintenance of high glucocorticoid levels during inflammation and sepsis. Finally, hypersecretion of cytokines that normally participate in the paracrine regulation of the adrenal cortex, together with ectopically or eutopically expressed receptors, constitute an unregulated trophic stimulus that can lead to hypercortisolism, hyperplasia, and tumorigenesis.

ISSN:1068-3097    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Traditionally, aldosterone action has been defined as unidirectional transepithelial sodium transport. Direct effects on the brain, such as raised blood pressure, and on the heart, such as cardiac fibrosis, have been observed in experimental studies on rats. In the recently published Randomized Aldactone Evaluation Study (RALES) trial, low doses of spironolactone (Aldactone, G.D. Searle Pharmaceuticals, Skokie, Illinois) produced a 30% improvement in morbidity and mortality rates when added to conventional best-practice treatment for patients with moderate to severe heart failure. Even at low (25 mg) doses, Aldactone is often associated with an unacceptable incidence of gynecomastia, reflecting its ability to act as an androgen receptor antagonist as well as a mineralocorticoid receptor antagonist. Given the experimental and clinical evidence for a cardioprotectant effect of mineralocorticoid receptor blockade, epoxymexrenone (Eplerenone, G.D. Searle Pharmaceuticals, Skokie, Illinois) has been developed as a selective aldosterone receptor antagonist, with 10 to 100-fold higher receptor specificity than spironolactone and with equivalentin vivopotency in humans and in rats.

ISSN:1068-3097    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Adrenal-based mineralocorticoid excess that is not secondary to excessive angiotensin II or adrenocorticotrophic hormone (ACTH) exists primarily as primary aldosteronism (PAL) and rarely as deoxycorticosterone-secreting adrenal tumor. The availability and wide application of the plasma aldosterone—plasma renin activity (PRA) ratio as a screening test for PAL has led to the recent recognition that PAL is common, possibly accounting for 5 to 10% of patients with hypertension, with most normokalemic. Detection and appropriate management of PAL relies on (1) screening of all patients with hypertension and not just those with hypokalemia or resistant hypertension; (2) confirmation of PAL using a reliable diagnostic approach such as fludrocortisone suppression testing (saline infusion testing may lack sensitivity); and (3) careful further assessment to differentiate the subtype, including genetic testing for the hybrid gene that causes glucocorticoid-remediable aldosteronism, and adrenal venous sampling to differentiate unilateral from bilateral aldosterone overproduction. The establishment of other underlying genetic mutations and new genetic tests should also aid in the detection of PAL and potentially curable hypertension.

ISSN:1068-3097    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:1068-3097    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Gonadotropin-releasing hormone (GnRH) is a decapeptide that is synthesized and released from specific neurons in the hypothalamus. It is responsible for the pituitary expression of the gonadotropins, luteinizing hormone, and follicle-stimulating hormone. In turn, these gonadotropins 1) signal the gonads to synthesize and release estrogen or testosterone and 2) stimulate gametogenesis. Complex feedback mechanisms operate at the level of the hypothalamus and pituitary. The molecular mechanisms that translate environmental and metabolic cues into changes in GnRH expression are beginning to be elucidated. Many studies have contributed to our understanding of the control mechanisms for the expression of hypothalamic GnRH. The advent of transformed cultured GnRH-expressing cell lines has certainly spirited the field forward, and the ability to use molecular techniques to study GnRH gene expressionin vivohas further advanced the field. Studies in infertile patients have identified genes that may be important in GnRH gene expression and that, therefore, may play an etiologic role in hypothalamic hypogonadism.

ISSN:1068-3097    

出版商:OVID    

年代:2000

数据来源: OVID