Abstract:
:At the early stage of its development in 1957, the daily dose of spironolactone necessary to improve various pathological conditions was not precisely determined and dose-dependent sexual side effects limited its long-term use. Prescription of high daily doses and absence of selectivity for the mineralocorticoid receptor explain these limitations. The 9-11alpha epoxy group added to mexrenone by the Ciba-Geigy chemists in 1984 and improved chemical synthesis at Searle, permitted the original international clinical development of a selective antagonist for high blood pressure and congestive heart failure treatment. This review deals with the main methodological issues of a 20-year biological and clinical development of eplerenone, the second antimineralocorticoid drug. The investigation of a large range of daily doses (25-400mg) initially selected in normal volunteers by the 9alpha-fluorohydrocortisone test has led to the conclusion that 50-100mg q.i.d. doses of eplerenone offer a favorable benefit/risk ratio in various patient populations by neutralization of the aldosterone effects on blood pressure and target organ damage. The absence of sexual side-effects has confirmed the clinical relevance of the initial biological hypothesis on the need for more selectivity at the androgen and progestogen receptor sites. Widening the distance between efficacy and adverse effects of an anti-mineralocorticoid drug will facilitate the long-term maintenance of a moderately negative sodium balance and a slightly positive potassium balance, while minimizing the direct effects of salt and aldosterone on the heart, vessels, brain, and kidneys. Wide use in unselected patients and additional controlled clinical trials are necessary to confirm the benefits expected from animal and clinical research given that a 45-year interval also characterizes the story of the Na-Cl cotransporter (NCC) blocker, chlorthalidone, from its initial clinical use to the demonstration of its beneficial effects on cardiovascular morbidity and mortality.
journal_name
Mol Cell Endocrinoljournal_title
Molecular and cellular endocrinologyauthors
Ménard Jdoi
10.1016/j.mce.2003.10.008keywords:
subject
Has Abstractpub_date
2004-03-31 00:00:00pages
45-52issue
1-2eissn
0303-7207issn
1872-8057pii
S0303720703003794journal_volume
217pub_type
历史文章,杂志文章abstract:OBJECTIVES:The aim of this study is to address the role of low-density lipoprotein (LDL) on mouse preimplantation embryos. METHODS:The temporal expression of low-density lipoprotein receptor (LDLR) and side-chain cleavage cytochrome P450 (P450scc) mRNAs in mouse oocytes and preimplantation embryos up to the hatched bl...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/s0303-7207(03)00082-0
更新日期:2003-04-28 00:00:00
abstract::We investigated the effect of pretreatment of immature rats with 5 or 50 micrograms nafoxidine (UA), or with 0.05 micrograms 17 beta-estradiol (E2) on several uterine responses elicited by treatment with a test injection of 15 micrograms E2, administered 48 h after pretreatment. Early (6 h) and late (24 h) responses w...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(85)90053-x
更新日期:1985-10-01 00:00:00
abstract::The seminal vesicles of male rat secrete tissue-specific proteins under androgenic control. The effects of testosterone on the rough endoplasmic reticulum (RER) and Golgi-system of this tissue have been quantified using specific antibodies. Castration was followed within 2 weeks by a 10-fold reduction in RER-specific ...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(84)90124-2
更新日期:1984-08-01 00:00:00
abstract::Evidence from in vitro studies and naturally occurring human diseases indicate that several endocrine cells, and particularly somatotrophs, recognize cAMP as a growth factor. Accordingly, mutations of the alpha subunit of the stimulatory G protein gene (GNAS) leading to the constitutive activation of adenylyl cyclase ...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章,评审
doi:10.1016/j.mce.2010.04.009
更新日期:2010-09-15 00:00:00
abstract::Leptin, the adipocyte-derived hormone that plays a key role in body weight homeostasis, has recently emerged as a relevant neuroendocrine mediator in different systems, including the reproductive axis. Thus, compelling evidence points out a major role of leptin in the regulation of female pubertal development and fert...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章,评审
doi:10.1016/s0303-7207(02)00008-4
更新日期:2002-02-25 00:00:00
abstract::Human chorionic gonadotropin (hCG) is synthesized primarily in the placenta while human luteinizing hormone (hLH) is produced in the pituitary. Both hormones are highly homologous in structure and both appear to be altered to analogous molecular forms as the hormones are proteolytically processed, or metabolized, from...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章,评审
doi:10.1016/s0303-7207(96)03942-1
更新日期:1996-12-20 00:00:00
abstract::Peroxisome proliferator-activated receptors (PPAR)α have been shown to exert immunomodulatory effects in autoimmune disorders; no study evaluated the effect of PPARα activation in Graves' ophthalmopathy (GO). We show the presence of PPARα, δ and γ in GO fibroblasts and preadipocytes. PPARα activators have a potent inh...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2011.11.001
更新日期:2012-02-26 00:00:00
abstract::A cell culture line has been derived from lymphosarcoma P1798. Cells will not divide in the prescence of 10(-8) M dexamethasone. Half-maximal inhibition of proliferation occurs at about 10(-9) M. Half-maximal inhibition of [3H] thymidine incorporation occurs at somewhat higher concentrations of dexamethasone. When cel...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(80)90121-5
更新日期:1980-02-01 00:00:00
abstract::A critical regulatory component of the hypothalamus/pituitary/adrenal axis (HPA) in mammals, reptiles and birds, and in the hypothalamus/pituitary/interrenal (HPI) axis of amphibians and teleosts (modern bony fishes) is the strict ligand selectivity of the melanocortin-2 receptor (MC2R). Tetrapod and teleost MC2R orth...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章,评审
doi:10.1016/j.mce.2014.12.022
更新日期:2015-06-15 00:00:00
abstract::We previously demonstrated the interactions of different chemical compounds with estrogen receptors ERalpha and ERbeta and the androgen receptor (AR) using different reporter cell lines. In this study, we characterize the ERalpha, ERbeta and AR activity of different biphenyls using the same tools. We provide evidence ...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/s0303-7207(02)00094-1
更新日期:2002-07-31 00:00:00
abstract::Calcium homeostasis refers to the regulation of calcium ion concentration in the body. This concentration is tightly controlled by a stabilizing system consisting of calcium channels and calcium buffering proteins. Calcium homeostasis is crucial for cell survival. Various forms of cell death (e.g., necrosis and apopto...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2015.05.017
更新日期:2015-09-05 00:00:00
abstract::Transforming growth factor beta (TGF beta) caused a dose-dependent increase in both basal and follicle-stimulating hormone (FSH)-stimulated inhibin production by rat granulosa cells in culture. The TGF beta dose-response curve in the absence of FSH was approximately parallel to that in the presence of either a minimal...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(88)90150-5
更新日期:1988-08-01 00:00:00
abstract::The molecular basis of the organogenesis, homeostasis, and tumorigenesis of the adrenal cortex has been the subject of intense study for many decades. Specifically, characterization of tumor predisposition syndromes with adrenocortical manifestations and molecular profiling of sporadic adrenocortical tumors have led t...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章,评审
doi:10.1016/j.mce.2015.11.031
更新日期:2016-02-05 00:00:00
abstract::The Steroidogenic acute regulatory protein (StAR) directs mitochondrial cholesterol uptake through a C-terminal cholesterol binding domain (CBD) and a 62 amino acid N-terminal regulatory domain (NTD) that contains an import sequence and conserved sites for inner membrane metalloproteases. Deletion of the NTD prevents ...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章,评审
doi:10.1016/j.mce.2016.08.015
更新日期:2017-02-05 00:00:00
abstract::Environmental conditions in early life permanently alter the development of glucocorticoid receptor gene expression in the hippocampus and hypothalamic-pituitary-adrenal responses to acute or chronic stress. In part, these effects can involve an activation of ascending serotonergic pathways and subsequent changes in t...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章,评审
doi:10.1016/s0303-7207(01)00635-9
更新日期:2001-12-20 00:00:00
abstract::Parathyroid hormone-related protein (PTHrP) is produced by many tumors not associated with humoral hypercalcemia, including breast cancers. In this study, we used three human immortalized mammary epithelial cell lines that differ in tumorigenicity and PTHrP expression. Using RT-PCR we investigated 5' and 3' alternativ...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/s0303-7207(02)00298-8
更新日期:2003-06-30 00:00:00
abstract::The purpose of this paper is to review potential novel functional pathways by which estradiol and estrogenic compounds elicit biological responses in mammals. We will limit our approach to those novel functions suggested by phenotypes associated with estrogen receptor-alpha (ER alpha) gene mutations and polymorphisms....
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章,评审
doi:10.1016/s0303-7207(98)00170-1
更新日期:1998-10-25 00:00:00
abstract::Galectin-1 is highly expressed in blastocysts and trophoblast giant cells during implantation, and dysregulated galectin-1 is associated with many pregnancy-related abnormalities. Elevated galectin-1 contributes to cancer cells invasion. Here, we found that galectin-1 is expressed in mouse oocytes, preimplantation emb...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2017.11.003
更新日期:2018-07-15 00:00:00
abstract::This study examines the effect of FSH, testosterone and estradiol on testicular LH receptors and in vitro testicular responsiveness to LH in immature rats under various conditions. FSH treatment of 15-day-old immature rats significantly increased the number of LH receptors but did not alter testicular responsiveness. ...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(77)90004-1
更新日期:1977-10-01 00:00:00
abstract::The antiestrogen tamoxifen has been successfully used to control estrogen receptor (ER) and progesterone receptor positive breast cancer. However, the development of antiestrogen resistance is frequently observed in patients following long term treatment. We have studied the development of antiestrogen resistance in v...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(92)90104-e
更新日期:1992-12-01 00:00:00
abstract::Deficiency of adrenal hormones promotes exacerbated neutrophil influx into inflammatory sites. We investigated the effect of adrenal deficiency on neutrophil mobilization comparing adrenalectomized (ADX) male Wistar rats to sham-operated (SO) or non-manipulated (N) animals, as controls. Seven days after surgeries, the...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2006.01.007
更新日期:2006-04-25 00:00:00
abstract::In type 2 diabetes, a strong correlation between intramyocellular lipid accumulation and insulin resistance exists but whether intramyocellular accumulation is a cause or a consequence of insulin resistance is not clear. Lipid accumulation and response to insulin were evaluated in primary human myotubes derived from n...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2009.10.017
更新日期:2010-02-05 00:00:00
abstract::Administration of 0.1 or 1 mg of prednisolone to fed mice caused a 5-fold activation of glycogen synthase in the liver after 3h, without significant changes in the circulating levels of glucose or insulin, or the hepatic concentration of cyclic AMP. Adrenalectomized fasted rats responded to cortisol (10 mg) with an in...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(82)90067-3
更新日期:1982-06-01 00:00:00
abstract::Over the last 20 years, aromatase inhibitors have been developed to become a highly effective treatment strategy for treatment of hormone receptor positive breast cancer. Despite their success, poor response and resistance limit the effectiveness of these agents in up to 50% of patients. In recent years, studies using...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章,评审
doi:10.1016/j.mce.2010.12.034
更新日期:2011-07-04 00:00:00
abstract::Perfluorooctanoic acid (PFOA) is a persistent pollutant worldwide and even found in human cord blood and breast milk. Some animal studies have reported that PFOA causes developmental toxicity such as fetal weight loss, but the mechanism is still unclear. This study focused on developmental toxicity of PFOA, particular...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2011.01.009
更新日期:2011-04-30 00:00:00
abstract::Podocyte apoptosis in glomerular lesions has been found to have a dominant role in the progression of diabetic nephropathy. The present research aimed to explore the beneficial effect of icariin on diabetic podocytes by interfering in the process of apoptosis. Podocyte apoptosis was significantly exacerbated after hig...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2018.01.014
更新日期:2018-09-15 00:00:00
abstract::Bisphenol A (BPA) and para-Nonylphenol (p-NP) are chemicals of industrial origin which may influence human reproductive health. The effects of these substances in the prenatal life is an important topic that is receiving greater attention in the developed countries. In this study, human trophoblast cells HTR-8/SVneo w...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2015.05.023
更新日期:2015-09-05 00:00:00
abstract::The most potent, physiologic activator of proopiomelanocortin (POMC) gene transcription is corticotropin releasing hormone (CRH) and increased intracellular cAMP is critical for this effect. The 5'-flanking region of the murine POMC gene has several potential binding sites for regulatory proteins. To characterize the ...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(93)90224-8
更新日期:1993-11-01 00:00:00
abstract::The aim of this study was to examine the first step in steroidogenesis in male and female gonads of fetal rats. Pregnenolone production was measured by radioimmunoassay in organ culture, conversion of [3H]cholesterol to [3H]pregnenolone was evaluated in isolated mitochondria and cytochrome P-450scc was revealed by imm...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(90)90101-d
更新日期:1990-08-20 00:00:00
abstract::Using as a model system, primary cultures of porcine Leydig cells, we have shown that transforming growth factor-beta 1 (TGF-beta 1) (2 ng/ml, 72 h) antagonizes the stimulatory action of insulin-like growth factor-I (IGF-I) on luteinizing hormone (LH/hCG) receptors. We therefore investigated the action of TGF-beta 1 o...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(94)90015-9
更新日期:1994-03-01 00:00:00