Abstract:
:Altered cytochrome P450-catalyzed metabolism of 17beta-estradiol (E2) and estrone (E1) in the liver and (or) extrahepatic tissues may affect estrogen-sensitive tumorigenesis. We examined the effects of oral treatments of (i) indole-3-carbinol (13C) at 250 or 500 mg/kg or beta-naphthoflavone (beta-NF) at 40 mg/kg of body weight (bw)/day from 51 to 54 days of age (acute regimen), and (ii) 13C at 250 mg/kg or beta-NF at 20 mg/kg bw given 3x/week from 10 to 22 weeks of age (chronic regimen) in female Sprague-Dawley rats. We determined the effects of these treatments on the P450 content and P450 (CYP)-specific activities in the liver, P450-dependent metabolism of E2 and E1 by the liver and mammary gland, and interconversion of E1 and E2 catalyzed by 17beta-hydroxysteroid dehydrogenase (17beta-HSD) in these tissues and malignant mammary tumors. 13C at the two levels of acute regimen elicited similar responses. Acute and chronic treatments with 13C, but not beta-NF, increased P450 content approximately 2-fold. 13C, and to a lesser extent beta-NF, increased CYP1A1 and CYP1A2 probe activities in liver up to 117- and 27- fold, respectively, and after acute regimens, that of CYP3A by approximately 1.8-fold. 13C also increased activity of CYP2B up to 100-fold. Overall hepatic metabolism of E2 and E1, which was approximately 2-fold greater at 55 than 155 days of age, was increased (approximately 2.8-fold) by 13C with 2-, 4-, 16alpha-, 6alpha-, 6beta-, and 15alpha-hydroxy (OH) comprising > or = 54, 3, 2, approximately 2, approximately 5, 7, and 2%, respectively, of E1 and E2 metabolites. Acute regimens of beta-NF increased 2- and 15alpha-OH-E2 (62 and 5% of total) from E2 and 2-, 4-, and 6alpha-OH-E1 + 6beta-OH-E1 (32, 13, and 4% of total) from E1. Mammary gland metabolized E2 to E1 and small amounts of 15alpha-, 4-, 16alpha-, 6beta-, and 6alpha-OH-E2. After the acute IC3 regimen, E2 was also converted to 2-OH-E2. 17Beta-HSD-catalyzed oxidation of E2 was favored in the liver and reduction of E1 was favored in mammary gland and tumor (= 1% of hepatic activity). An increased (approximately 2-fold) ratio of reductive to oxidative activities in malignant mammary tumors by chronic 13C regimen may stimulate tumor growth. This is the first report showing that after chronic oral regimens, the 13C-, but not beta-NF-, induced changes in CYP complement led to elevated E2 and E1 metabolism. The persistent effects of increased putative carcinogenic and estrogenic 4- and 16alpha-OH as well as 6alpha- and 6beta-OH-E2 and 6beta-OH-E1 might counteract those of the less estrogenic 2-OH metabolites, thus accounting for the lack of suppression of mammary tumorigenesis by 13C in our previous study.
journal_name
Can J Physiol Pharmacoljournal_title
Canadian journal of physiology and pharmacologyauthors
Ritter CL,Prigge WF,Reichert MA,Malejka-Giganti Dsubject
Has Abstractpub_date
2001-06-01 00:00:00pages
519-32issue
6eissn
0008-4212issn
1205-7541journal_volume
79pub_type
杂志文章abstract::The goal of the present study was to assess the effects of a restricted feeding schedule (RFS) on postischemic contractile recovery in relation to triacylglycerol (TAG), glycogen, and ATP content. Glucose-6-phosphate dehydrogenase (G6PDH) activity, reduced/oxidized glutathione ratio (GSH/GSSG), and thiobarbituric acid...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/y10-076
更新日期:2010-10-01 00:00:00
abstract::The tau mutation in the golden (Syrian) hamster is a single gene mutation that drastically affects the speed of the circadian clock, in such a way that homozygous mutants have an endogenous circadian period of 20 h (compared with 24 h for wild-type hamsters). While studying the circadian system of tau-mutant hamsters ...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/cjpp-2013-0276
更新日期:2014-01-01 00:00:00
abstract::Insulin sensitivity and resistance were examined in vivo in uremic rats by using tracer methods which permit the assessment of "non-steady-state" glucose kinetics. By relating the changes in the rates of glucose output by the liver (Ra), uptake by tissues (Rd), and metabolic clearance (MCR) to immunoreactive glucagon ...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/y80-051
更新日期:1980-03-01 00:00:00
abstract::Sensorimotor mechanisms were studied on the basis of kinematic and electromyographic data as well as the static torque developed by the muscles as a function of joint angle. The latter relationship is known as the torque/angle characteristic. Fast single-joint movement may result from a shift in this characteristic an...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1139/y95-042
更新日期:1995-02-01 00:00:00
abstract::The major hallmark of rotator cuff tendinopathies (RCT) is the disorganization of tendon extracellular matrix (ECM) which is due to decrease in the collagen I-to-collagen III ratio. In addition, the pathology of tendon matrisome remains asymptomatic and hypoxia has been identified to be the priming signal to initiate ...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/cjpp-2020-0314
更新日期:2020-08-15 00:00:00
abstract::It has been proposed that medullary washout secondary to increased blood flow will limit maximal urine osmolality and reabsorption of salt and water from the inner medullary collecting duct. We have tested this prediction. The function of the inner medullary collecting duct was examined by microcatheterization. Acetyl...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/y87-383
更新日期:1987-12-01 00:00:00
abstract::The purposes of this review were twofold: to apply modern physicochemical principles to explain changes in acid-base regulation and the control of ventilation in human pregnancy; and to demonstrate the value of pregnancy as a model for the study of endocrine effects on physiological control systems. Application of P.A...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章,评审
doi:10.1139/cjpp-76-9-815
更新日期:1998-09-01 00:00:00
abstract::The developing heart forms during the early stages of embryogenesis, and misregulated heart development results in congenital heart defects (CHDs). To understand the molecular basis of CHDs, a deep understanding of the morphological and genetic basis of heart development is necessary. Atrial Natriuretic Factor (ANF) i...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章,评审
doi:10.1139/y11-051
更新日期:2011-08-01 00:00:00
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journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/Y10-057
更新日期:2010-08-01 00:00:00
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journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:
更新日期:1985-06-01 00:00:00
abstract::For 10 days, dogs were fed a normal salt diet containing 70 mequiv. Na+/day (NSD) followed by a high salt diet containing 170 mequiv. Na+/day (HSD) or 240 mequiv. Na+/day (VHSD), or the order was reversed. K+ in these diets was fixed at 40 mequiv./day. The different diets did not influence the basal level of serum cat...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/y80-164
更新日期:1980-09-01 00:00:00
abstract::This paper provides a brief overview of the adaptive control of prehension. Several primary issues for research in the field are considered. One pertains to the stages of prehensile activity, with particular concern for the kinematic control of precontact phases, and the coordination of load and grip forces following ...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章,评审
doi:10.1139/y94-074
更新日期:1994-05-01 00:00:00
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journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章,评审
doi:10.1139/y79-020
更新日期:1979-02-01 00:00:00
abstract::The area postrema (AP) is one of the circumventricular organs of the brain and as such it is highly vascular and lacks the normal blood-brain barrier. Anatomical tracing studies have demonstrated afferent projections to AP originating from the paraventricular nucleus, lateral parabrachial nucleus (l-PBN), nucleus trac...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章,评审
doi:10.1139/y91-153
更新日期:1991-07-01 00:00:00
abstract::The sarco(endo)plasmic reticulum calcium ATPase (SERCA) is responsible for transporting calcium (Ca(2+)) from the cytosol into the lumen of the sarcoplasmic reticulum (SR) following muscular contraction. The Ca(2+) sequestering activity of SERCA facilitates muscular relaxation in both cardiac and skeletal muscle. Ther...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章,评审
doi:10.1139/cjpp-2014-0463
更新日期:2015-10-01 00:00:00
abstract::This study examined whether the effects of FK506-binding protein dissociation from sarcoplasmic reticulum (SR) Ca(2+) release channels on excitation-contraction (EC) coupling changed when SR Ca(2+) reuptake and (or) the trans-sarcolemmal Ca(2+) extrusion were altered. The steady-state twitch Ca(2+) transient (CaT), ce...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/y05-020
更新日期:2005-04-01 00:00:00
abstract::The metabolic effect of intravenous infusion of ammonium chloride (60 mumol/(kg body weight.min] was compared in five sheep before and after adrenal denervation. Adrenal denervation completely abolished the hyperglycemic effect of ammonium chloride, diminished the rise of pyruvate and lactate concentration, and failed...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/y89-168
更新日期:1989-09-01 00:00:00
abstract::A significant relationship was observed between myocardial oxygen extraction and the extravascular mean time transit time. This relationship implies that oxygen extraction by the myocardium is a time-dependent process, and emphasizes the critical link between blood flow and myocardial oxygen consumption. ...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/y77-068
更新日期:1977-06-01 00:00:00
abstract::Neonatal hyperthyroidism in rats induced by daily administration of L-triiodothyronine for 30 days since birth resulted in a significant rise in mobility and the metabolism of brain norepinephrine and dopamine. Whereas administration of lithium carbonate (60 mg/kg ip) to normal rats for 6 days produced no effect on sp...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/y77-070
更新日期:1977-06-01 00:00:00
abstract::In Western societies, the incidence of diet-related diseases is progressively increasing due to greater availability of hypercaloric food and a sedentary lifestyle. Obesity, diabetes, atherosclerosis, and neurodegeneration are major diet-related pathologies that share a common pathogenic denominator of low-grade infla...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章,评审
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更新日期:2013-06-01 00:00:00
abstract::The effects of modafinil on heat thermoregulatory responses were studied in 10 male subjects submitted to a sweating test after taking 200 mg of modafinil or placebo. Sweating tests were performed in a hot climatic chamber (45 degrees C, relative humidity <15%, wind speed = 0.8 m x s(-1), duration 1.5 h). Body tempera...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 临床试验,杂志文章
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更新日期:2002-08-01 00:00:00
abstract::Rats were treated daily with atropine (2.5 mg/kg), imipramine (5 mg/kg), viloxazine (5 mg/kg), or saline for 14 days. Thirty-six hours following the final injection the rats were anaesthetized with urethane and the sensitivity of neurones in the somatosensory cortex to iontophoretically applied acetylcholine (ACh) was...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/y80-087
更新日期:1980-05-01 00:00:00
abstract::Tolerance to ethanol was induced in male Sprague-Dawley rats (225-250 g) by chronic feeding with a liquid diet containing 6.5% ethanol (v/v). Control rats were pair-fed with a liquid diet in which the ethanol was replaced by an equicaloric concentration of sucrose. Immediately following sacrifice of the animals the ne...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/y83-145
更新日期:1983-09-01 00:00:00
abstract::Chronically hypoxic rats (exposed to 5000 m elevation for 3 weeks) develop pulmonary hypertension (PH) that is reversed upon return to normoxia and is blocked by bradykinin (BK) antagonist B9430 treatment (100 microg/kg s.c. three times per week). Treatment of rats with both the synthetic VEGF receptor-1/2 antagonist ...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/y02-047
更新日期:2002-04-01 00:00:00
abstract::We investigated whether cell-to-cell coupling between myometrial cells of parturient rats is influenced by intracellular adenosine 3',5'-cyclic monophosphate (cAMP) concentration. To evaluate the coupling, we measured input resistance (Ro) and injected Lucifer Yellow (LY) using microelectrode techniques. The intercell...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/y92-045
更新日期:1992-03-01 00:00:00
abstract::The LA/N-corpulent (LA/N-cp) rat is a normotensive strain derived from Koltesky's original mutant strain of the spontaneously hypertensive rat (SHR). When homozygous for the cp gene (cp/cp), the rats are hyperphagous, hyperlipidemic, hyperinsulinemic, and obese. The rats have been shown, by scanning electron microscop...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/y86-215
更新日期:1986-10-01 00:00:00
abstract::The neural connections from the medial prefrontal cortex to the ventral pallidum were investigated in urethane-anesthetized rats. Extracellular recordings were made from 124 spontaneously firing neurons in the ventral pallidum while the medial prefrontal cortex was electrically stimulated. The most frequent response t...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/y93-053
更新日期:1993-05-01 00:00:00
abstract::The effects of 5-hydroxytryptamine (5-HT) on spinal motoneurons were examined in pentobarbital-anaesthetized cats and in nonanaesthetized decerebrate cats by intracellular recording and extracellular iontophoresis of 5-HT. 5-HT first induced a depolarization and then a long-lasting hyperpolarization (up to 60 min) wit...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/y91-022
更新日期:1991-02-01 00:00:00
abstract::Exercise is a powerful therapy for preventing the onset of and slowing the progression of cardiovascular disease. Increased shear stress during exercise improves vascular homeostasis by both decreasing reactive oxygen species and increasing nitric oxide bioavailability in the endothelium. While these observations are ...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章,评审
doi:10.1139/cjpp-2013-0486
更新日期:2014-07-01 00:00:00
abstract::The isometric potentiation associated with myosin phosphorylation is force dependent. The purpose of this study was to assess the influence of a pre-existing period of isometric force on the concentric force potentiation displayed by mouse muscles with and without the ability to phosphorylate myosin. We tested isometr...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/cjpp-2014-0118
更新日期:2015-01-01 00:00:00