Abstract:
:The 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta HSD-2) enzyme is thought to confer aldosterone specificity upon mineralocorticoid target tissues by protecting the mineralocorticoid receptor from binding by the more abundant glucocorticoids, corticosterone and cortisol. We have developed a Chinese hamster ovary cell line stably transfected with a plasmid containing the rat 11 beta HSD-2 complementary DNA. This cell line has expressed the enzyme consistently for many generations. The 11 beta HSD-2 was located primarily in the microsomes, but significant amounts also existed in the nuclei and mitochondria. The enzymatic reaction was unidirectional, oxidative, and inhibited by the product, 11-dehydrocorticosterone, with an IC50 of approximately 200 nM. The K(m) for corticosterone was 9.6 +/- 3.1 nM, and that for NAD+ was approximately 8 microM. The enzyme did not convert dexamethasone to 11-dehydrodexamethasone. Tunicamycin, an N-glycosylation inhibitor, had no effect on enzyme activity. 11 alpha-Hydroxyprogesterone (11 alpha OH-P) was an order of magnitude more potent a competitive inhibitor of the 11 beta HSD-2 than was glycyrrhetinic acid (GA) (approximate IC50 = 0.9 vs. 15 nM). 11 beta OH-P, progesterone, and GA were almost equipotent (IC50 = 10 and 6 nM, respectively), and 5 alpha-pregnandione and 5 beta-pregnandione were less potent (IC50 = 100 and 500 nM, respectively) inhibitors of the enzyme. When the inhibitory activities were examined with intact transfected cells, 11 alpha OH-P was more potent than GA (IC50 = 5 and 150 nM, respectively). 11 alpha OH-P was not metabolized by 11 beta HSD-2. We were unable to demonstrate the presence of 11 alpha OH-P in human urine. In conclusion, a cell line stably transfected with the rat 11 beta HSD-2 was created, and the enzyme kinetics, including inhibition, were characterized. 11 alpha OH-P was found to be a potent relatively specific inhibitor of the 11 beta HSD-2 enzyme. Its potential importance is that it is the most specific inhibitor of the 11 beta HSD-2 so far encountered and would aid in the study of the physiological importance of the isoenzyme.
journal_name
Endocrinologyjournal_title
Endocrinologyauthors
Morita H,Zhou M,Foecking MF,Gomez-Sanchez EP,Cozza EN,Gomez-Sanchez CEdoi
10.1210/endo.137.6.8641180subject
Has Abstractpub_date
1996-06-01 00:00:00pages
2308-14issue
6eissn
0013-7227issn
1945-7170journal_volume
137pub_type
杂志文章相关文献
ENDOCRINOLOGY文献大全abstract::Studies were performed to determine whether the postovulatory secretion of FSH in the rabbit is an LHRH-mediated event. Does were mated and then injected at 12 and 18 h postcoitum with pentobarbital (30 mg/kg BW), an agent known to block endogenous LHRH release. The injection of this barbiturate had no measurable effe...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-113-3-1020
更新日期:1983-09-01 00:00:00
abstract::Two receptors (CRH receptor type 1 and CRH receptor type 2) have been identified for the stress-induced neuropeptide, CRH and related peptides, urocortin, and urocortin II. We previously found marked down-regulation of cardiac CRH receptor type 2 expression following administration of bacterial endotoxin, lipopolysacc...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.142.8.8342
更新日期:2001-08-01 00:00:00
abstract::The direct effects of glucocorticoids on testicular LH receptor content and steroidogenesis were studied in vivo and in vitro. Immature hypophysectomized rats were treated with varying doses of dexamethasone, corticosterone, or a synthetic progestin, 17,21-dimethyl-19-nor-pregna-4,9-diene-3,20-dione (R5020). Some anim...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-108-6-2142
更新日期:1981-06-01 00:00:00
abstract::Ovarian angiotensin I (Ang I)-converting enzyme (ACE), estimated by the specific binding of the ACE inhibitor [125I]iodo-MK-351A, is localized on multiple ovarian structures, including follicular granulosa cells, corpora lutea, terminal epithelium, and ovarian blood vessels, but total ovarian ACE does not display a cy...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-126-6-2927
更新日期:1990-06-01 00:00:00
abstract::The effect of collagenase dissociation of virgin mouse mammary glands on the level of mammary epithelial cytosolic estrogen receptors (ER) and progesterone receptors (PR) was assessed. After cell dissociation, ER was present in mammary epithelial cells at concentrations similar to those found in the whole gland. Howev...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-116-1-105
更新日期:1985-01-01 00:00:00
abstract::PTH increases calcium reabsorption exclusively in the distal nephron. Two mechanisms of Ca++ transport through the basolateral membrane (BLM) have been described: the ATP-dependent and the sodium gradient-dependent transport. In the present study, we investigated the effect of PTH and (Bu)2cAMP on these two mechanisms...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-128-1-251
更新日期:1991-01-01 00:00:00
abstract::Previously, a human CYP3A4-transgenic (Tg-CYP3A4) mouse line was reported to exhibit enhanced metabolism of midazolam by cytochrome P450 3A4 (CYP3A4) expressed in small intestine. Here we show that expression of CYP3A4 and murine cyp3a and cyp2b was both age and sex dependent. CYP3A4 was expressed in the livers of mal...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2004-1248
更新日期:2005-07-01 00:00:00
abstract::p-Tyramine, an endogenous amine with sympathomimetic action, is found in the mammalian hypothalamus. When injected ip, p-tyramine reduced serum PRL without altering LH and TSH serum titers in adult orchidectomized rats and rats subjected to ether or immobilization stress. The hyperprolactinemia achieved by this last p...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-116-5-2044
更新日期:1985-05-01 00:00:00
abstract::ACTH and cAMP stimulate steroidogenesis and the mitochondrial electron transport system for steroid hydroxylation in cultured mouse adrenal cortex tumor cells. During this stimulation, the biosynthesis of adrenodoxin, a non-heme iron protein which is one of the electron transport enzymes, was examined. 14C-labeled adr...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-99-4-977
更新日期:1976-10-01 00:00:00
abstract::Although prolactinomas can be effectively treated with dopamine agonists, about 20% of patients develop dopamine resistance or tumor recurrence after surgery, indicating a need for better understanding of underlying disease mechanisms. Although estrogen-induced rat prolactinomas have been widely used to investigate th...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2012-1056
更新日期:2012-08-01 00:00:00
abstract::In the rat ovary, follicle cells produce and respond to activin, but as yet, the functional significance of the autocrine/paracrine effects of ovarian activin remains equivocal. To assess the effects of activin on folliculogenesis, normal cycling female rats were injected once every 8 h over a 40-h period with recombi...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.136.11.7588210
更新日期:1995-11-01 00:00:00
abstract::In mammals, adrenal medulla chromaffin cells constitute a fundamental component of the sympathetic nervous system outflow, producing most of the circulating adrenaline. We recently found that the rhesus monkey adrenal gland expresses several genes in a 24-h rhythmic pattern, including TH (the rate-limiting enzyme in c...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2007-0610
更新日期:2007-12-01 00:00:00
abstract::To probe the possible role of endogenous opiates in Sertoli cell proliferation during testicular development, the effect of interfering with beta-endorphin action either in vivo or in vitro was determined. The percent of Sertoli cells dividing was measured with quantitative autoradiography in [methyl 3H]-thymidine-exp...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-119-4-1876
更新日期:1986-10-01 00:00:00
abstract::Glutathione (GSH) is the most abundant intracellular thiol and an important regulator of cellular redox status. Mice that lack the modifier subunit of glutamate cysteine ligase (Gclm), the rate-limiting enzyme in GSH synthesis, have decreased GSH synthesis. Nicotinamide nucleotide transhydrogenase, an inner mitochondr...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2011-0207
更新日期:2011-07-01 00:00:00
abstract::The concentration-activity profiles for insulin and insulin-like growth factor I (IGF-I; in the presence of and insulin-like growth factor I (IGF-I; in the presence of hydrocortisone and PRL) have been compared in terms of the accumulation of beta-casein mRNA, total casein synthesis, and alpha-lactalbumin and basal ca...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-120-4-1411
更新日期:1987-04-01 00:00:00
abstract::In the present study, we investigated the role of the multidrug resistance (mdr) P-glycoprotein (Pgp) at the blood-brain barrier in the control of access of cortisol and corticosterone to the mouse and human brain. [(3)H]Cortisol poorly penetrated the brain of adrenalectomized wild-type mice, but the uptake was 3.5-fo...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.142.6.8213
更新日期:2001-06-01 00:00:00
abstract::Local release of TGF-beta during times of high bone turnover leads to elevated levels within the bone microenvironment, and we have shown that TGF-beta suppresses osteoclast apoptosis. Therefore, understanding the influences of TGF-beta on bone resorbing osteoclasts is critical to the design of therapies to reduce exc...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2009-0813
更新日期:2010-04-01 00:00:00
abstract::In various forms of shock, TRH is equivalent to naloxone in reversing the hypotension and improving the survival rate. The present findings indicate that in spontaneously hypertensive rats (SHR), TRH has another naloxone-like effect in antagonizing the antihypertensive response to clonidine and alpha-methyldopa. When ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-115-6-2481
更新日期:1984-12-01 00:00:00
abstract::Kisspeptin neurons play an essential role in the regulation of fertility through direct regulation of the GnRH neurons. However, the relative contributions of the two functionally distinct kisspeptin neuron subpopulations to this critical regulation are not fully understood. Here we analyzed the specific projection pa...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2015-1131
更新日期:2015-07-01 00:00:00
abstract::We previously characterized the transcriptional activity of the human CRH (hCRH) gene promoter in the mouse anterior pituitary cell line AtT20. Here, we show that phorbolester stimulated through the cAMP response element (CRE), located between -227 and -220 relative to the putative cap site, about 2.6-fold the express...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.132.1.8380380
更新日期:1993-01-01 00:00:00
abstract::The role of calcium in the angiotensin II- or potassium-mediated increase in aldosterone production was analyzed in isolated glomerulosa cells prepared from bovine adrenal glands. The response to potassium was highly dependent on the extracellular calcium concentration, and a maximal response was observed at 0.5 mM ca...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-109-6-2196
更新日期:1981-12-01 00:00:00
abstract::In rodents, soluble leptin receptor (SLR) may be generated by alternative splicing of ObR mRNA and/or as a cleavage product of ObR membrane-anchored receptors. In this study, we investigated the contribution of both processes on the generation of SLR in 3-, 8-, and 24-month-old Wistar rats fed ad libitum (AL) or under...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2005-0220
更新日期:2005-11-01 00:00:00
abstract::We compared the somatomedin (SM) activity of perfusates of livers from normal and hypophysectomized (hypox) rats with and without the addition of growth hormone (GH) to the perfusions. Livers were perfused for a total of 3 hours, with a change of Waymouth's medium MB 752/l every 30 min, in a continously recirculating ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-98-3-606
更新日期:1976-03-01 00:00:00
abstract::In the present study we examined the mechanisms involved in the activation of the hypothalamo-pituitary-adrenal (HPA) axis after administration of the glucose analog 2-deoxyglucose (2-DG), which inhibits intracellular glucose use. Adult male rats were injected with either 2-DG (400 mg/kg body wt ip) or vehicle and wer...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.134.4.8137760
更新日期:1994-04-01 00:00:00
abstract::The expression of cholesterol side-chain cleavage cytochrome P450 (P450scc), 17 alpha-hydroxylase cytochrome P450 (P45017 alpha), and 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) was studied in bovine placenta and fetal adrenal glands throughout gestation. The levels of expression of these enzymes were much lower ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.130.5.1374010
更新日期:1992-05-01 00:00:00
abstract::The concentrations of ACTH and cortisol both rise in the plasma of fetal lambs during late pregnancy, reflecting maturation of the fetal hypothalamic-pituitary-adrenal axis and providing the stimulus for parturition. The failure of rising cortisol to suppress plasma ACTH may be due to altered sensitivity of glucocorti...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-126-1-11
更新日期:1990-01-01 00:00:00
abstract::The antitumor properties of antibodies to the beta-subunit of hCG (hCG beta) coupled to tetanus toxoid (tt) were studied in hamsters implanted with the BeWo strain of human choriocarcinoma. After active immunization with hCG beta-tt mixed in complete Freund's adjuvant, hamsters synthesized large quantities of antibodi...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-106-1-150
更新日期:1980-01-01 00:00:00
abstract::We reported previously that chromogranin A (Chga) knockout (KO) mice are hypertensive and hyperadrenergic. Here we sought to determine the basis of such alterations by probing physiological, biochemical, and pharmacological responses to perturbations of the autonomic nervous system. In the conscious state, KO mice had...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2009-0429
更新日期:2009-11-01 00:00:00
abstract::We investigated the effects of acute (24-h) peroxisome proliferator-activated receptor (PPAR)alpha activation by WY14,643 (pirinixic acid) treatment on glucose-stimulated insulin secretion (GSIS) during pregnancy, in the rat, in relation to insulin sensitivity. GSIS after iv glucose challenge (500 mg/kg) was increased...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2002-220811
更新日期:2003-01-01 00:00:00
abstract::The effect of 3 alpha-hydroxy-4-pregnen-20-one (3HP), a Sertoli cell steroid, on the secretion of gonadotropins from rat anterior pituitary cells in culture was examined and subsequently compared with the action of other gonadal steroids and steroids structurally related to 3HP. Pituitary cells from randomly cycling, ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-125-1-41
更新日期:1989-07-01 00:00:00