Abstract:
:To study the physiological regulation of the iodothyronine 5'-deiodinases (I-5'D), we have examined the effects of some thiol blockers and of thyroid status on I-5'D activities both in vitro and in vivo. At low (less than 5 mM) concentrations of dithiothreitol, propylthiouracil (PTU) inhibited I-5'D in the brain, pituitary, and brown adipose tissue (BAT) of hypothyroid rats (which contain predominantly the type II activity); the patterns of inhibition in these tissues were essentially similar, with a Ki of about 174 microM at 250 microM dithiothreitol. Hydroxyethyldisulfide was a strong inhibitor of the type II enzyme, with relatively little effect on the renal enzyme at both high concentrations (micromolar) of T4, i.e. predominantly type I activity, and low concentrations (nanomolar) to T4, i.e. both type I and low Km activity. Preincubation of cerebral microsomes with PTU, followed by removal of excess PTU, resulted in 70% inhibition of I-5'D activity in cerebral microsomes at 5 mM dithiothreitol; the corresponding inhibitions of the renal enzyme at high and low substrate concentrations were 66% and 48%, respectively. Specific binding of PTU to renal and cerebral microsomes was diminished by hydroxyethyldisulfide, but not by T4, suggesting that PTU binding was not dependent on substrate interaction. Administration of PTU in vivo (1 mg/100 g BW, ip; 1 h before killing) resulted in approximately 80% inhibition of I-5'D activity in renal microsomes at high T4, and 50-70% inhibition in pituitary, BAT, and renal microsomes at low T4, but no inhibition was observed in brain microsomes. HPLC analyses revealed a PTU content of 35-65 nmol/g wet wt in the pituitary, BAT, liver, and kidney, but no PTU was detected in the brain, suggesting that PTU may be excluded by the blood-brain barrier. Maintaining hypothyroid rats on 1 microgram T4/100 g BW.day for 5 days enhanced renal type I and low Km I-5'D with restoration of serum T3 to normal levels, although the type II I-5'Ds from all sources were severely depressed. A supraphysiological dose of T4 depressed all three I-5'Ds. The data indicate that the I-5'Ds are regulated in a qualitatively similar fashion.
journal_name
Endocrinologyjournal_title
Endocrinologyauthors
Goswami A,Rosenberg INdoi
10.1210/endo-126-5-2597subject
Has Abstractpub_date
1990-05-01 00:00:00pages
2597-606issue
5eissn
0013-7227issn
1945-7170journal_volume
126pub_type
杂志文章相关文献
ENDOCRINOLOGY文献大全abstract::In adult male rhesus monkeys, 1 day of fasting leads to a profound suppression of LH secretion that is rapidly reversed with refeeding. To test the hypothesis that changes in insulin secretion during fasting and refeeding mediate the changes in LH secretion, blood samples for LH measurement were obtained between 0900-...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.137.6.8641210
更新日期:1996-06-01 00:00:00
abstract::The maternal plasma concentrations of GH and PRL increase dramatically upon the initiation of lactation in the rat. In light of the fact that these two hormones have evolved from one common precursor, we sought to determine if the neuroendocrine mechanisms regulating their concomitant increase during lactation are com...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-124-1-464
更新日期:1989-01-01 00:00:00
abstract::5-Hydroxytryptamine (5-HT) is synthesized and secreted by thyroid parafollicular (PF) cells. As all PF granules contain 5-HT, it is released whenever PF cells secrete. Because 5-HT stimulates follicular (F) cells and can modulate their response to TSH, 5-HT has been proposed to be a paracrine PF to F cell transmitter....
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.137.10.8828510
更新日期:1996-10-01 00:00:00
abstract::This study was designed to investigate the role of dopaminergic mechanisms in the control of aldosterone secretion. Six rhesus monkeys received metoclopramide (1.25 mg, iv), with 5% dextrose (vehicle) or with dopamine (4 micrograms/kg . min) infusions begun 60 min before the administration of the dopamine antagonists....
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-110-4-1173
更新日期:1982-04-01 00:00:00
abstract::Hypothalamic lesions or deficient melanocortin (MC) signaling via MC4 receptor (MC4r) mutations often lead to hyperphagia and severe treatment-resistant obesity. We tested the methionine aminopeptidase 2-inhibitor beloranib (ZGN-440) in 2 male rat models of obesity, one modeling hypothalamic obesity with a combined me...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2016-1665
更新日期:2017-01-01 00:00:00
abstract::During preimplantation development in the mouse, it is crucial that glucose metabolism not be compromised. Any decrease in glucose uptake at this stage in development can compromise the developing embryo. We have cloned another member of the glucose transporter family, GLUT9, which is expressed embryonically. Three di...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2003-1264
更新日期:2004-03-01 00:00:00
abstract::Insulin coordinates the complex response to feeding, affecting numerous metabolic and hormonal pathways. Forkhead box protein O1 (FoxO1) is one of several signaling molecules downstream of insulin; FoxO1 drives gluconeogenesis and is suppressed by insulin. To determine the role of FoxO1 in mediating other actions of i...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2017-00870
更新日期:2018-03-01 00:00:00
abstract::Leptin, a circulating 16-kDa protein secreted by adipocytes, decreases body weight by reducing food intake and enhancing energy utilization. Leptin receptors that share homology to the glycoprotein gp130 have been recently cloned. In addition, differentially spliced leptin receptor messenger RNAs have been identified....
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.138.8.5343
更新日期:1997-08-01 00:00:00
abstract::Male Sprague-Dawley rats were injected ip with 1 microgram pertussis toxin (PTX)/100 g BW. The rats were killed 24, 48, and 72 h after injection, and their pancreases were removed. At each time point, insulin secretion by isolated islets was measured under basal and glucose-stimulated conditions and in the absence and...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.136.5.7720630
更新日期:1995-05-01 00:00:00
abstract::The purpose of this experiment was to determine whether surgical stress on the morning of proestrus would elicit an early release of gonadotropin from the pituitary. Animals exhibiting 5-day estrous cycles underwent bilateral sham-ovariectomy under ether anesthesia at 0800 h of proestrus. These animals had high levels...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-97-3-718
更新日期:1975-09-01 00:00:00
abstract::To examine the mechanism of estrogen's direct stimulation of steroidogenesis in the rabbit corpus luteum, we tested the hypothesis that the effect of estrogen on progestin production occurs at the site of processing of the precursor for pregnenolone (i.e. cholesterol) in the mitochondrion. For this purpose, we manipul...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-122-5-1948
更新日期:1988-05-01 00:00:00
abstract::The formation of a new blood supply, angiogenesis, is an essential component of carcinogenesis and unrestricted tumor growth. A substance capable of inhibiting angiogenesis would be of considerable therapeutic potential in the treatment of cancer. We previously reported that the 16-kilodalton N-terminal fragment of ra...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.133.3.7689950
更新日期:1993-09-01 00:00:00
abstract::The estrogenic and antiestrogenic actions of the geometric isomers of tamoxifen and 4-hydroxytamoxifen were determined in a PRL synthesis assay using primary cultures of dispersed immature rat pituitary gland cells. 4-Hydroxytamoxifen was 100 times more potent as an antiestrogen than tamoxifen. The cis isomer of tamox...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-122-4-1449
更新日期:1988-04-01 00:00:00
abstract::SH2-containing inositol 5'-phosphatase 2 (SHIP2) is a 5'-lipid phosphatase hydrolyzing the phosphatidylinositol (PI) 3-kinase product PI(3,4,5)P(3) to PI(3,4)P(2) in the regulation of insulin signaling, and is shown to be increased in peripheral tissues of diabetic C57BL/KSJ-db/db mice. To clarify the impact of SHIP2 ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2007-0820
更新日期:2008-02-01 00:00:00
abstract::ACTH produced a 75% increase in pregnenolone biosynthesis from endogenous precursors in isolated cells prepared from the rat Snell adrenocortical carcinoma 494. On the addition of 24- and 25-hydroxycholesterol to the tumor cells, the rate of pregnenolone synthesis increased 10-fold but was insensitive to the presence ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-105-5-1230
更新日期:1979-11-01 00:00:00
abstract::We have shown that nonlactogenic rat (r) GH is far more potent than rPRL in inducing rat mammary development. To determine the relative roles of GH and PRL in mammary development and their mechanisms of action, we have compared the abilities of a group of native and mutant GHs, PRLs, and placental lactogens (PLs) to i...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.133.4.8404600
更新日期:1993-10-01 00:00:00
abstract::The present work aimed to determine the role played by protein kinase-C (PKC) in the alpha 1-adrenoceptor-induced activation of hepatic metabolism. The following observations indicate that activation of PKC is a condition necessary for alpha 1-adrenoceptor activation of hepatic functions, but not sufficient to mimic t...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.133.5.8404660
更新日期:1993-11-01 00:00:00
abstract::Nucleic acid-based therapies offer great potential for treatment of a variety of diseases including cancer by modulating protein expression with DNA or small interfering RNA. However, realization of their full therapeutic potential is currently limited due to an inability to reach the target site in an active form. Id...
journal_title:Endocrinology
pub_type: 杂志文章,评审
doi:10.1210/en.2009-1045
更新日期:2010-02-01 00:00:00
abstract::We have studied regulation of the glucose transporter by thyroid hormone in ARL 15 cells, a thyroid hormone-responsive cell line derived from rat liver, T3 treatment (5 x 10(-8) M for 48 h) of confluent cell monolayers grown in thyroid hormone-deficient medium increased the rate of uptake of [3H] 2-deoxyglucose by 2.3...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-126-3-1421
更新日期:1990-03-01 00:00:00
abstract::Newborn male rats were treated SC with dexamethasone phosphate (100 microgram) or dexamethasone acetate (100 microgram) on postnatal day 1, dexamethasone phosphate (5.0 microgram) opn postnatal days 1, 2, 3, or the corresponding drug vehicle. All animals were sacrificed 65-70 days later at previously determined daily ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-108-3-1055
更新日期:1981-03-01 00:00:00
abstract::Since hypophysectomy and GH deficiency are associated with decreases in hypothalamic content and release of SRIF, it was of interest to determine whether these hormonal alterations also affect peripheral tissue levels of SRIF. Hypophysectomized (hypox) rats were studied at various times after surgery and compared with...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-115-6-2260
更新日期:1984-12-01 00:00:00
abstract::Cyclin D1 encodes the regulatory subunit of a holoenzyme that phosphorylates and inactivates the retinoblastoma protein and promotes progression through the G1-S phase of the cell cycle. Amplification or overexpression of cyclin D1 plays pivotal roles in the development of a subset of human cancers including parathyro...
journal_title:Endocrinology
pub_type: 杂志文章,评审
doi:10.1210/en.2004-0959
更新日期:2004-12-01 00:00:00
abstract::The effect of beta-endorphin upon plasma arg8-vasopressin release was studied in vivo in rabbits and in vitro in rat neural lobes. Following intravenous administration of 200 mug/kg synthetic beta-endorphin plasma AVP rose significantly by five minutes after injection and remained elevated for twenty-five minutes comp...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-101-5-1643
更新日期:1977-11-01 00:00:00
abstract::The estrogen receptor (ER) mixed agonists tamoxifen and raloxifene have been shown to protect against bone loss in ovariectomized rats. However, the mechanism by which these compounds manifest their activity in bone is unknown. We have used a series of in vitro screens to select for compounds that are mechanistically ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.138.9.5358
更新日期:1997-09-01 00:00:00
abstract::Androgens and estrogens play major roles in cell differentiation, cell growth, and peptide secretion in steroid target tissues. In addition to the binding of these hormones to their receptors, formation and metabolism are important in the action of steroids. Metabolism of the potent steroid hormones includes glucuroni...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.142.2.7958
更新日期:2001-02-01 00:00:00
abstract::We previously found that the sustained rise in active sodium transport by the toad urinary bladder after exposure to insulin is associated with the synthesis of a membrane protein with a molecular weight of 25,000. Studying the effects of insulin on the incorporation of uridine into RNA of epithelial cells of the blad...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-109-6-2167
更新日期:1981-12-01 00:00:00
abstract::The influence of administration of ovine prolactin in vivo on intestinal fluid and ion transport in vitro was investigated using intact and hypophysectomized male rats. Prolactin administration significantly stimulated fluid, sodium,potassium, calcium, magnesium and chloride transport across everted jejunal sacs. The ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-96-5-1158
更新日期:1975-05-01 00:00:00
abstract::Adult rats which have received monosodium-L-glutamate (MSG, 4 mg/g BW) on alternate days for the first 10 days of life manifest central nervous system lesions largely restricted to the retina and the arcuate nucleus of the hypothalamus in which nearly 90% of the perikarya are destroyed, leaving axons in passage intact...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-103-1-170
更新日期:1978-07-01 00:00:00
abstract::Activin A is a dimeric protein hormone that regulates numerous cellular functions. A clear physiological role for this molecule in pregnancy is suggested by previous studies in the human, wherein activin A rises dramatically as women approach parturition. To determine whether the rodent is a suitable animal model for ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.138.7.5231
更新日期:1997-07-01 00:00:00
abstract::A myometrial explant culture system was developed to investigate the effect of progesterone and the antiprogestagen RU486 on prostacyclin (PGI2) and thromboxane A2 (TXA2) synthesis by the rat myometrium. After culture, eicosanoid synthesis was stimulated with arachidonic acid (AA) and the calcium ionophore A23187 (A23...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-119-2-655
更新日期:1986-08-01 00:00:00