Abstract:
:Effects of spironolactone, canrenone and canrenoate-K on adrenal cytochrome P450 (P450) and corticosteroid biosynthesis were examined by studying difference spectra, P450 reduction and corticoid hydroxylation in mitochondrial preparations isolated from zona fasciculata and zona glomerulosa of bovine adrenals and from adrenal adenoma and hyperplastic adrenal cortex removed from patients with hyperaldosteronism. All three agents bound to P450 producing type I difference spectra and underwent hydroxylation. They all inhibited 11beta-hydroxylation in bovine adrenal at 30 muM and higher concentrations. Canrenone, the most potent inhibitor, blocked enzyme activity by 60% at a concentration of 60 muM. Spironolactone stimulated P450 reduction. The order of potency of inhibition was found to correlate with the order of affinity of these agents for P450. 11beta-Hydroxylase in human adrenal appeared to be less sensitive to canrenone. All three agents or their hydroxylated metabolites blocked 18-hydroxylation in bovine adrenal at lower concentrations. Canrenoate-K, being the most effective, inhibited 52% at 20 muM. Low concentrations of canrenone (2.5-5.0 muM) were without effect on 11beta-hydroxylase but markedly inhibited 18-hydroxylation (62-76%) in hyperplastic human adrenals. The inhibitors produced mixed type inhibition of 11beta-hydroxylation and competitive type inhibition of 18-hydroxylation. These findings indicate that at low concentrations spironolactone and its major metabolites, canrenone and canrenoate-K, or their hydroxylated metabolites, can directly interfere with the biosynthesis of aldosterone in bovine and certain human adrenal cortical tissue.
journal_name
Endocrinologyjournal_title
Endocrinologyauthors
Cheng SC,Suzuki K,Sadee W,Harding BWdoi
10.1210/endo-99-4-1097subject
Has Abstractpub_date
1976-10-01 00:00:00pages
1097-106issue
4eissn
0013-7227issn
1945-7170journal_volume
99pub_type
杂志文章相关文献
ENDOCRINOLOGY文献大全abstract::Mammary gland is an organ that undergoes cycles of growth, differentiation, and function during pregnancy and lactation. Although it is known that the gland enhances its sensitivity to insulin during lactation, it remains to be investigated whether this increased sensitivity develops during pregnancy and which are the...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.139.2.5735
更新日期:1998-02-01 00:00:00
abstract::Mutations in the GnRH receptor gene (GNRHR) can result in hypogonadotropic hypogonadism in humans. Unlike most mammals, mice lack a second form of GnRH (GnRH2) and a type 2 GnRH receptor. To determine whether the GnRH receptor is critical at all stages of reproduction and whether this receptor has additional physiolog...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2009-0598
更新日期:2010-03-01 00:00:00
abstract::Rabbit hearts perfused by the Langendorff technique were studied. The addition of ovine prolactin (NIH-P-S-10) to the perfusate in a concentration of 50 ng/ml produced rapid increases in both the amplitude and rate of contraction in 33 adult male hearts studied in winter. Prepubertal male animals showed no response, a...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-97-4-1008
更新日期:1975-10-01 00:00:00
abstract::Obesity is often associated with an impairment of the hypothalamic-pituitary-gonadal axis. The leptin-deficient ob/ob mouse model is characterized by a morbid obesity with a sterility in males and females that is corrected by continuous leptin treatment. Since ob/ob mice are maintained on the C57BL/6J inbred genetic b...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.140.2.6470
更新日期:1999-02-01 00:00:00
abstract::Benign prostatic hyperplasia (BPH) is an age-related debilitating prostatic disease that is frequently associated with prostatic inflammation and bothersome lower urinary tract symptoms (LUTS). Animal models have shown that formalin- and bacterial-induced prostatic inflammation can induce bladder dysfunction; however,...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endocr/bqaa212
更新日期:2021-01-01 00:00:00
abstract::Peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1), a cold-induced protein expressed in brown adipose tissue (BAT), plays a role in adaptive thermogenesis by up-regulating uncoupling proteins (UCP). Here, we explore its relationship to the thermogenic actions of leptin, which also up-regulates UCPs...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.141.12.7804
更新日期:2000-12-01 00:00:00
abstract::The insulin-like growth factor-binding proteins (IGFBPs) comprise at least six distinct species that may modulate the action of IGFs. IGFs are important regulators of fetal growth and differentiation. To define sites of IGFBP mRNA synthesis, we have used in situ hybridization techniques in mouse conceptuses of differe...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.132.6.7684980
更新日期:1993-06-01 00:00:00
abstract::Previous studies have shown that the adenylyl cyclase of intact granulosa cells from immature porcine follicles has a uniquely prolonged responsiveness to FSH and an atypically poor responsiveness to cholera toxin relative to other cells. The present studies were designed to determine if these characteristics were due...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-118-1-302
更新日期:1986-01-01 00:00:00
abstract::Recent studies using twins and inbred strains of mice reveal evidence for genetic mechanisms contributing to variation in circulating levels of IGF-I, IGF-II, and IGF binding protein (IGFBP)-3. To examine the hypothesis that serum IGFBP-5 levels have a strong heritable component, we intercrossed two inbred strains of ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2003-0042
更新日期:2003-08-01 00:00:00
abstract::Selective serotonin-reuptake inhibitors (SSRIs) antagonize the serotonin (5-hydroxytryptamine) transporter (5-HTT), and are frequently prescribed to children and adolescents to treat depression. However, recent findings of functional serotonergic pathways in bone cells and preliminary clinical evidence demonstrating d...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2004-1259
更新日期:2005-02-01 00:00:00
abstract::Molecular mechanisms underlying unloading-induced reduction of bone formation have not yet been fully understood. In vitro, Runx2 has been suggested to be involved in mechanical signaling in osteoblasts. However, the roles of Runx2 in vivo during the bone response to mechanical stimuli have not yet been known. The pur...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2005-1020
更新日期:2006-05-01 00:00:00
abstract::The present study was undertaken to investigate the effect of the Hyp mutation and diet-induced hyperparathyroidism on renal responsiveness to PTH and forskolin and to determine whether the renal brush border membrane phosphate transport defect is expressed in the vitamin D- and calcium-deficient Hyp mouse. Our result...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-118-3-1047
更新日期:1986-03-01 00:00:00
abstract::Posttranslational modifications of prolactin (PRL), including phosphorylation, vary with physiologic state and alter biologic activity. In light of the growing evidence for a role for PRL in proliferation in mammary cancer, we examined the ability of a mimic of phosphorylated human PRL, S179D-PRL, to initiate signals ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2003-0826
更新日期:2003-12-01 00:00:00
abstract::Thyroid hormone produces a prompt, plasma membrane-mediated increase in several metabolic functions in the rat thymocyte. These effects of thyroid hormone require calcium and are inhibited by the beta-adrenergic antagonist alprenolol. In the present study, the interrelationship between thyroid hormone and adrenergic a...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-122-5-2240
更新日期:1988-05-01 00:00:00
abstract::In vivo and in vitro evidence indicates that FSH is a primary regulator of testicular inhibin production. However, recent reports suggest that LH may also promote inhibin secretion in vivo. To investigate whether LH regulates inhibin subunit messenger RNA (mRNA) expression as well, we examined the effects of hypophyse...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-127-3-1097
更新日期:1990-09-01 00:00:00
abstract::Hereditary vitamin D-resistant rickets (HVDRR) is an autosomal recessive disease caused by mutations in the vitamin D receptor (VDR). We studied a young Saudi Arabian girl who exhibited the typical clinical features of HVDRR, but without alopecia. Analysis of her VDR gene revealed a homozygous T to C mutation in exon ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2004-0080
更新日期:2004-11-01 00:00:00
abstract::Pineal denervation by superior cervical ganglionectomy (Gx) decreased high affinity binding of estradiol (E2) to the pineal cytosol of female rats and of testosterone to the cytosol of male rats by 40 and 26% and by 75 and 80%, 5 and 14 days after sugery; hormone binding remained unchanged up to 24 h after surgery. Bi...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-98-4-849
更新日期:1976-04-01 00:00:00
abstract::Transcriptional regulation of metabolic genes in the liver is the key to maintaining systemic energy homeostasis during starvation. The membrane-bound transcription factor cAMP-responsive element-binding protein 3-like 3 (CREB3L3) has been reported to be activated during fasting and to regulate triglyceride metabolism...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2014-1113
更新日期:2014-12-01 00:00:00
abstract::Diets lacking soy and alpha-alpha derivatives that are considered to be estrogen-free by standard bioassays (uterotrophic assay and vaginal opening) have been revealed to contain considerable amounts of compounds able to transcriptionally activate the estrogen receptors (ERs) and stimulate luciferase expression in sev...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2005-0660
更新日期:2005-12-01 00:00:00
abstract::Removal of fetuses at day 14 of gestation (Ftx14) in the pregnant rat leads to a marked suppression of serum levels of rat placental lactogen (rPL-II). One might attribute this to compromised placental growth in the absence of a fetus. However, if ovariectomy and fetectomy (Ftx14 Ovx14) are carried out at the same tim...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-114-1-22
更新日期:1984-01-01 00:00:00
abstract::Glucose stimulation of pancreatic beta-cells triggers electrical activity (slow waves of membrane potential with superimposed spikes) that is best monitored with intracellular microelectrodes. Closure of ATP-sensitive K+ channels underlies the depolarization to the threshold potential and participates in the increase ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.139.3.5783
更新日期:1998-03-01 00:00:00
abstract::Decidualization, the process by which fibroblastic human endometrial stromal cells (HESC) differentiate into secretory decidual cells, is a critical event during the establishment of pregnancy. It is dependent on the steroid hormone progesterone acting through the nuclear progesterone receptor (PR). Previously, we ide...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endocr/bqz021
更新日期:2020-01-01 00:00:00
abstract::Synthesis of uteroglobin in rabbit uterine epithelial cells during early pregnancy is induced by progesterone and apparently suppressed by estrogen. To assess whether the steroid hormones exert regulatory effects on the expression of the uteroglobin gene, we performed transcriptional rate assays in endometrial nuclei ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-112-3-871
更新日期:1983-03-01 00:00:00
abstract::The effects of LH on glucose metabolism within cumulus cell-enclosed bovine oocytes were determined. Cumulus cell-enclosed bovine oocytes were matured in vitro (IVM) in control medium alone or supplemented with LH, FSH, or TSH, then individually assayed for the metabolism of D-[5-3H]glucose, D-[1-14C]glucose, D-[6-14C...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.131.6.1446610
更新日期:1992-12-01 00:00:00
abstract::Whereas the stimulatory effect of interleukin-6 (IL-6) on the hypothalamic-pituitary-adrenal (HPA) axis is well established, its mode of action in this axis has yet to be fully elucidated. To further study the role of IL-6 in the HPA axis, we compared the expression of IL-6 messenger RNA (mRNA) in the rat hypothalamus...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.133.6.8243280
更新日期:1993-12-01 00:00:00
abstract::An estrogen-binding macromolecule was identified in cytosolic fractions prepared from fetal rat lung tissue. This component sedimented at 4.5S on sucrose gradients and was heat labile and proteinaceous in nature. This estrogen-binding protein bound 17 beta-estradiol (Ka = 10(8) M-1) and estrone but had little or no af...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-109-1-210
更新日期:1981-07-01 00:00:00
abstract::Altered leptin action has been implicated in the pathophysiology of heart failure in obesity, a hallmark of which is extracellular matrix remodeling. Here, we characterize the direct influence of leptin on matrix metalloproteinase (MMP) activity in primary adult rat cardiac fibroblasts and focus on elucidating the mol...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2010-1166
更新日期:2011-05-01 00:00:00
abstract::G proteins were quantitated by immunoblot in normal rat anterior pituitary, an estrone-induced pituitary adenoma, and in two transplantable pituitary tumors resistant to dopamine, 7315a and MtTW15. Antisera specific for the alpha o and beta subunits or the alpha i subunit of G proteins were tested with all preparation...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-122-3-1176
更新日期:1988-03-01 00:00:00
abstract::Recent evidence suggests that the aromatization of testosterone to estrogen is important for the organizing effects of neonatal testosterone on neuroendocrine responses to acute challenges. However, the extent to which neonatal inhibition of aromatase alters the stress-induced activation of neural pathways has not bee...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2011-1749
更新日期:2012-04-01 00:00:00
abstract::The effects of GH and PTH on cancellous histomorphometry were determined in the proximal tibial metaphysis of hypophysectomized (HYPOX) sexually mature female rats. HYPOX resulted in uterine atrophy and a loss in body weight. Longitudinal bone growth ceased and bone formation was greatly reduced. There were decreases ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.136.11.7588250
更新日期:1995-11-01 00:00:00