Constitutive Androstane Receptor and Pregnane X Receptor Gene Expression in Human Liver: Interindividual Variability and Correlation with CYP2B6 mRNA Levels

2003 ◽  
Vol 31 (1) ◽  
pp. 7-10 ◽  
Author(s):  
Thomas K. H. Chang ◽  
Stelvio M. Bandiera ◽  
Jie Chen
Keyword(s):  
Gene Expression ◽  
Human Liver ◽  
Interindividual Variability ◽  
Receptor Gene ◽  
Constitutive Androstane Receptor ◽  
Pregnane X Receptor ◽  
Mrna Levels ◽  
Receptor Gene Expression

scholarly journals Characterization and Regulation of Type A Endothelin Receptor Gene Expression in Bovine Luteal Cell Types

Endocrinology ◽  
1999 ◽  
Vol 140 (5) ◽  
pp. 2110-2116 ◽  
Author(s):  
Roni Mamluk ◽  
Nitzan Levy ◽  
Bo Rueda ◽  
John S. Davis ◽  
Rina Meidan
Keyword(s):  
Gene Expression ◽  
Receptor Gene ◽  
Cell Types ◽  
Cell Populations ◽  
Mrna Levels ◽  
Factor I ◽  
Receptor Mrna ◽  
Progesterone Production ◽  
Eta Receptor ◽  
Receptor Gene Expression

Abstract Our previous studies demonstrated that endothelin-1 (ET-1), a 21-amino acid vasoconstrictor peptide, has a paracrine regulatory role in bovine corpus luteum (CL). The peptide is produced within the gland where it inhibits progesterone production by acting via the selective type A endothelin (ETA) receptors. The present study was designed to characterize ETA receptor gene expression in different ovarian cell types and its hormonal regulation. ETA receptor messenger RNA (mRNA) levels were high in follicular cells as well as in CL during luteal regression. At this latter stage, high ETA receptor expression concurred with low prostaglandin F2α receptor mRNA. The ETA receptor gene was expressed by all three major cell populations of the bovine CL; i.e. small and large luteal cells, as well as in luteal endothelial cells. Among these various cell populations, the highest ETA receptor mRNA levels were found in endothelial cells. cAMP elevating agents, forskolin and LH, suppressed ETA receptor mRNA expression in luteinized theca cells (LTC). This inhibition was dose dependent and was evident already after 24 h of incubation. In luteinized granulosa cells (LGC), 10 and 100 ng/ml of insulin-like growth factor I and insulin (only at a concentration of 2000 ng/ml) markedly decreased ETA receptor mRNA levels. In both LGC and LTC there was an inverse relationship between ETA receptor gene expression and progesterone production; insulin (in LGC) and forskolin (in LTC) enhanced progesterone production while inhibiting ETA receptor mRNA levels. Our findings may therefore suggest that, during early stages of luteinization when peak levels of both LH and insulin-like growth factor I exist, the expression of ETA receptors in the gland are suppressed. This study demonstrates physiologically relevant regulatory mechanisms controlling ETA receptor gene expression and further supports the inhibitory role of ET-1 in CL function.

scholarly journals Circulating leptin during ovine pregnancy in relation to maternal nutrition, body composition and pregnancy outcome

2001 ◽  
Vol 169 (3) ◽  
pp. 465-476 ◽  
Author(s):  
L Thomas ◽  
JM Wallace ◽  
RP Aitken ◽  
JG Mercer ◽  
P Trayhurn ◽  
...  
Keyword(s):  
Gene Expression ◽  
Body Composition ◽  
Adipose Tissue ◽  
Dietary Intake ◽  
Leptin Receptor ◽  
Maternal Nutrition ◽  
Receptor Gene ◽  
Mrna Levels ◽  
Tissue Samples ◽  
Receptor Gene Expression

This study examined the pattern of circulating leptin in age-matched sheep during adolescent pregnancy, and its relationship with maternal dietary intake, body composition and tissue expression of the leptin gene. Overfeeding the adolescent pregnant ewe results in rapid maternal growth at the expense of the placenta, leading to growth restriction in the fetus, compared with normal fed controls. Our results demonstrate that, in the adolescent ewe, overfeeding throughout pregnancy was associated with higher maternal leptin concentrations, when compared with moderately fed controls (P<0.05), with no peak in circulating leptin towards the end of pregnancy. There was a close correlation between indices of body composition and circulating leptin levels at day 104 of gestation and at term (P<0.03). Further, when the dietary intake was switched from moderate to high, or high to moderate, at day 50 of gestation, circulating leptin levels changed rapidly, in parallel with the changes in dietary intake. Leptin mRNA levels and leptin protein in perirenal adipose tissue samples, taken at day 128 of gestation, were higher in overfed dams (P<0.04), suggesting that adipose tissue was the source of the increase in circulating leptin in the overnourished ewes. Leptin protein was also detected in placenta but leptin gene expression was negligible. However, leptin receptor gene expression was detected in the ovine placenta, suggesting that the placenta is a target organ for leptin. A negative association existed between maternal circulating leptin and fetal birth weight, placental/cotyledon weight and cotyledon number. In conclusion, in this particular ovine model, hyperleptinaemia was not observed during late pregnancy. Instead, circulating leptin concentrations reflected increased levels of leptin secretion by adipose tissue primarily as a result of the increase in body fat deposition, due to overfeeding. However, there appears to be a direct effect of overfeeding, particularly in the short term. In the nutritional switch-over study, circulating leptin concentrations changed within 48 h of the change in dietary intake. The presence of leptin protein and leptin receptor gene expression in the placenta suggests that leptin could be involved in nutrient partitioning during placental and/or fetal development.

scholarly journals Modulation of glomerular endothelin and endothelin receptor gene expression in aminonucleoside-induced nephrosis.

1995 ◽  
Vol 5 (8) ◽  
pp. 1585-1590
Author(s):  
T Nakamura ◽  
I Ebihara ◽  
M Fukui ◽  
S Osada ◽  
Y Tomino ◽  
...  
Keyword(s):  
Gene Expression ◽  
Receptor Gene ◽  
Mrna Level ◽  
Experimental Period ◽  
Receptor Expression ◽  
Mrna Levels ◽  
Puromycin Aminonucleoside ◽  
Receptor Mrna ◽  
Etb Receptor ◽  
Receptor Gene Expression

This study assessed glomerular endothelin (ET)-1, ET-3, and ET-receptor A and B mRNA levels in puromycin aminonucleoside (PAN)-induced nephrosis. During the nephrotic stage, 8 days after PAN injection, ET-1 and ETB receptor mRNA were elevated by 2.8 +/- 0.8-fold (P < 0.01) and 2.4 +/- 0.9-fold (P < 0.01), respectively, as compared with controls. These mRNA levels decreased to control levels by Day 20, when the nephrosis was in remission. In contrast, glomerular ETA receptor mRNA levels did not change in PAN nephrosis or control rats during the experimental period. ET-3 mRNA was not detected in the glomeruli of PAN nephrosis or control rats. Additionally, plasma ET concentration and glomerular ET production were measured in PAN nephrosis and control rats by radio-immunoassay. Eight days after PAN injection, ET-1 levels in plasma and glomeruli were not significantly altered in rats with PAN-induced nephrosis (glomeruli, 104.68 +/- 16.46 pg/mg of protein versus 98.24 +/- 13.68 pg/mg of protein; plasma, 2.68 +/- 1.10 versus 2.52 +/- 0.98 pg/mL). The administration of methylprednisolone to PAN rats resulted in the rapid disappearance of proteinuria and partially attenuated the increased ET-1 and ETB receptor gene expression in the glomeruli. These data indicate that glomerular ET-1 and ETB receptor expression in PAN nephrosis in increased at the mRNA level and that methylprednisolone treatment results in an attenuated increase.

scholarly journals PDGF ligand and receptor gene expression during repair of arterial injury.

1990 ◽  
Vol 111 (5) ◽  
pp. 2149-2158 ◽  
Author(s):  
M W Majesky ◽  
M A Reidy ◽  
D F Bowen-Pope ◽  
C E Hart ◽  
J N Wilcox ◽  
...  
Keyword(s):  
Gene Expression ◽  
Carotid Artery ◽  
Receptor Gene ◽  
Receptor Expression ◽  
Quiescent State ◽  
Mrna Levels ◽  
Luminal Surface ◽  
Receptor Mrna ◽  
Beta Receptor ◽  
Receptor Gene Expression

Smooth muscle cells (SMC) in rat carotid artery leave the quiescent state and proliferate after balloon catheter injury, but the signals for mitogenesis are not known. In this study, the possibility that cells within damaged arteries produce a growth factor that could act locally to stimulate SMC replication and repair was examined. We found that the genes for PDGF-A and -B (ligand) and PDGF receptor (alpha and beta subunits) were expressed in normal and injured carotid arteries and were independently regulated during repair of carotid injury. Two phases of PDGF ligand and receptor gene expression were observed: (a) In the early stage, a large decrease in PDGF beta-receptor mRNA levels preceded 10- to 12-fold increases in PDGF-A transcript abundance in the first 6 h after wounding. No change in PDGF alpha-receptor or PDGF-B gene expression was found at these times. (b) In the chronic phase, 2 wk after injury, neointimal tissue had lower levels of PDGF alpha-receptor mRNA (threefold) and higher levels of PDGF beta-receptor mRNA (three- to fivefold) than did restored media. Moreover, in situ hybridization studies identified a subpopulation of neointimal SMC localized at or near the luminal surface with a different pattern of gene expression than the underlying carotid SMC. Luminal SMC were strongly positive for PDGF-A and PDGF beta-receptor transcripts, while showing little or no hybridization for PDGF-B or PDGF alpha-receptor. Immunohistochemical studies showed strongly positive staining for PDGF-A in SMC along the luminal surface. These data show that changes in PDGF ligand and receptor expression occur at specific times and locations in injured carotid artery and suggest that these changes may play a role in regulating arterial wound repair.

scholarly journals Regulation of angiotensin II type 2 receptor gene expression in the adrenal medulla by acute and repeated immobilization stress

2012 ◽  
Vol 215 (2) ◽  
pp. 291-301 ◽  
Author(s):  
Regina Nostramo ◽  
Andrej Tillinger ◽  
Juan M Saavedra ◽  
Ashok Kumar ◽  
Varunkumar Pandey ◽  
...  
Keyword(s):  
Gene Expression ◽  
Angiotensin Ii ◽  
Receptor Gene ◽  
Receptor Expression ◽  
Mrna Levels ◽  
Ang Ii ◽  
Catecholamine Biosynthesis ◽  
Receptor Mrna ◽  
Receptor Gene Expression

While the renin–angiotensin system is important for adrenomedullary responses to stress, the involvement of specific angiotensin II (Ang II) receptor subtypes is unclear. We examined gene expression changes of angiotensin II type 1A (AT1A) and type 2 (AT2) receptors in rat adrenal medulla in response to immobilization stress (IMO). AT2 receptor mRNA levels decreased immediately after a single 2-h IMO. Repeated IMO also decreased AT2 receptor mRNA levels, but the decline was more transient. AT1A receptor mRNA levels were unaltered with either single or repeated IMO, although binding was increased following repeated IMO. These effects of stress on Ang II receptor expression may alter catecholamine biosynthesis, as tyrosine hydroxylase and dopamine β-hydroxylase mRNA levels in PC12 cells are decreased with Ang II treatment in the presence of ZD7155 (AT1 receptor antagonist) or with CGP42112 (AT2 receptor agonist) treatment. Involvement of stress-triggered activation of the hypothalamic–pituitary–adrenocortical or sympathoadrenal axis in AT2 receptor downregulation was examined. Cultured cells treated with the synthetic glucocorticoid dexamethasone displayed a transcriptionally mediated decrease in AT2 receptor mRNA levels. However, glucocorticoids are not required for the immediate stress-triggered decrease in AT2 receptor gene expression, as demonstrated in corticotropin-releasing hormone knockout (Crh KO) mice and hypophysectomized rats, although they can regulate basal gene expression. cAMP and pituitary adenylate cyclase-activating polypeptide also reduced AT2 receptor gene expression and may mediate this response. Overall, the effects of stress on adrenomedullary AT1A and AT2 receptor expression may contribute to allostatic changes, such as regulation of catecholamine biosynthesis.

Regulation of insulin-like growth factor-I and growth hormone receptor gene expression by diabetes and nutritional state in rat tissues

1989 ◽  
Vol 122 (3) ◽  
pp. 651-656 ◽  
Author(s):  
K. E. Bornfeldt ◽  
H. J. Arnqvist ◽  
B. Enberg ◽  
L. S. Mathews ◽  
G. Norstedt
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Receptor Gene ◽  
Mrna Levels ◽  
Factor I ◽  
Receptor Mrna ◽  
Gh Receptor ◽  
Igf I ◽  
Receptor Gene Expression ◽  
Different Tissues

ABSTRACT Insulin-like growth factor-I (IGF-I) mRNA and GH receptor mRNA levels were analysed in different tissues from rats made diabetic with streptozotocin, fasted rats and rats fed with a protein-reduced diet. Diabetes decreased IGF-I mRNA levels in liver, heart, diaphragm, kidney and aorta, but not in brain. GH receptor mRNA levels were decreased in heart and diaphragm, but not in liver and kidney. Fasting decreased IGF-I mRNA in all tissues studied except brain, and decreased GH receptor mRNA in liver, heart and diaphragm, but not in kidney. A protein-reduced diet decreased hepatic IGF-I mRNA levels but did not significantly affect other tissues, while GH receptor mRNA levels were reduced in liver and diaphragm. In conclusion, both diabetes and limited nutrition affected IGF-I and GH receptor mRNA in different tissues, but the two mRNAs were not co-ordinately regulated in all tissues studied. While reduced GH receptor gene expression may thus be responsible for decreased IGF-I gene expression in some states and tissues, additional regulatory mechanisms may be of importance. Journal of Endocrinology (1989) 122, 651–656

Modulation of epidermal growth factor binding and receptor gene expression by hormones and growth factors in sheep pituitary cells

1994 ◽  
Vol 143 (3) ◽  
pp. 489-496 ◽  
Author(s):  
S S Chaidarun ◽  
M C Eggo ◽  
P M Stewart ◽  
M C Sheppard
Keyword(s):  
Gene Expression ◽  
Growth Factors ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Receptor Gene ◽  
Pituitary Cells ◽  
Mrna Levels ◽  
High Affinity ◽  
Epidermal Growth ◽  
Receptor Gene Expression

Abstract Epidermal growth factor (EGF) is a potent mitogen for sheep pituitary cells but the factors controlling the binding and expression of EGF and its receptor (EGFR) in the pituitary are poorly understood. Regulation of EGF binding and EGFR gene expression may determine cellular responsiveness to EGF and could play a role in neoplastic development. Scatchard analysis of 125I-EGF binding in cultured sheep pituitary cells revealed two receptor binding sites (high affinity class of 2·5± 0·5 × 103 receptors/cell with a dissociation affinity constant (Kd) of 3·2± 0·7 × 1010m and low affinity class of 3·3 ±1·0 × 104 receptors/cell with a Kd of 71 ±1·3 × 10−9 m). Exposure of the cultured cells to some target gland hormones of the pituitary (oestrogen, tri-iodothyronine and hydrocortisone), pituitary growth factors (EGF, basic fibroblast growth factor, transforming growth factor-β and a tumour-promoting phorbol ester (TPA) resulted in an increase in the binding affinity of the high affinity receptors while reducing the receptor number and also a reduction of EGFR mRNA levels, shown by Northern blot analysis. In contrast, forskolin, an activator of adenylate cyclase, showed no significant effect on EGF binding and receptor gene expression. We conclude that the EGFR in normal pituitary cells can be modulated by several hormones and other growth factors at both receptor binding and mRNA levels. Transmodulation of EGFR by hormones and growth factors in the pituitary may be one of the regulatory mechanisms controlling the balance of normal pituitary growth and function. Defects in this regulatory system could have a role in the multistep process of pituitary tumourigenesis. Journal of Endocrinology (1994) 143, 489–496

scholarly journals Pituitary Hormone Gene Expression and Secretion in Human Growth Hormone-Releasing Hormone Transgenic Mice: Focus on Lactotroph Function1

Endocrinology ◽  
2000 ◽  
Vol 141 (1) ◽  
pp. 81-90 ◽  
Author(s):  
Joseph P. Moore ◽  
Aihua Cai ◽  
Mary Ellen Hostettler ◽  
Lydia A. Arbogast ◽  
James L. Voogt ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tyrosine Hydroxylase ◽  
Transgenic Mice ◽  
Transgenic Mouse ◽  
Anterior Pituitary ◽  
Receptor Gene ◽  
D2 Receptor ◽  
Mrna Levels ◽  
Receptor Mrna ◽  
Receptor Gene Expression

Abstract The human GH-releasing hormone (hGHRH) transgenic mouse has a hyperplastic anterior pituitary gland that eventually develops into an adenoma. We showed previously that the number of lactotrophs in the male hGHRH transgenic mouse is increased 2-fold, yet there is no concomitant increase in plasma levels of PRL. To further elucidate underlying changes in lactotroph function in the hGHRH transgenic mouse, the objectives of this study were to 1) examine the relative differences in PRL gene expression in transgenic mice and their siblings, 2) quantify PRL secretion at the level of the individual cell, 3) determine whether tyrosine hydroxylase gene expression and/or activity are altered in the hypothalamus of transgenic mice, and 4) assess dopamine receptor gene expression and functional sensitivity in lactotrophs of transgenic mice. Total PRL messenger RNA (mRNA) levels were increased nearly 5-fold in the hGHRH transgenic mouse, whereas the concentrations of PRL mRNA (PRL mRNA per μg total RNA) were unchanged. In contrast, total PRL contents were unchanged, whereas the concentrations of PRL (micrograms of PRL per mg total protein) were decreased 3-fold. Hypothalamic tyrosine hydroxylase steady state mRNA levels were not altered in the hGHRH transgenic mice, but hypothalamic tyrosine hydroxylase activity was increased 2-fold in transgenic mice. Dopamine D2 receptor mRNA concentrations in the anterior pituitary were increased 2.5-fold in hGHRH transgenic mice, and total pituitary D2 receptor mRNA levels were increased nearly 10-fold. Furthermore, the basal secretory capacity of lactotrophs from transgenic mice was increased significantly at the level of the single cell, and dopamine inhibited the secretion of PRL to a greater extent in hGHRH transgenic mice. Thus, although the total number of lactotrophs is increased 2-fold in hGHRH transgenic mice, the present data are consistent with the hypothesis that increased hypothalamic dopamine synthesis and release coupled with an increase in D2 dopamine receptor gene expression and functional sensitivity in the pituitary result in normal plasma levels of PRL.

Regulation of adiponectin receptor gene expression in diabetic mice

2005 ◽  
Vol 288 (5) ◽  
pp. E876-E882 ◽  
Author(s):  
Kouichi Inukai ◽  
Youhei Nakashima ◽  
Masaki Watanabe ◽  
Nobuki Takata ◽  
Takahiro Sawa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Receptor Gene ◽  
Inhibitory Effect ◽  
Northern Blotting ◽  
Mitogen Activated Protein Kinase ◽  
Adiponectin Receptor ◽  
Mrna Levels ◽  
Diabetic Mice ◽  
Receptor Gene Expression

Adiponectin is an adipocyte-derived factor that plays pivotal roles in lipid and glucose metabolism in muscle and liver. The following two adiponectin receptor types were recently identified: AdipoR1 is abundantly expressed in muscle, whereas AdipoR2 is predominantly expressed in the liver. To clarify the regulation of adiponectin receptor gene expression in diabetic states, we examined mRNA levels of AdipoR1 in the muscles of diabetic animals by Northern blotting. The level of AdipoR1 mRNA was increased ∼2.5-fold in muscle of streptozotocin (STZ) diabetic mice, but the normal level was restored by insulin administration, indicating that insulin has an inhibitory effect on AdipoR1 expression. To confirm this inhibitory effect of insulin, we performed in vitro experiments using C2C12 skeletal muscle cells. Insulin treatment for 24 h decreased AdipoR1 expression by ∼60% in C2C12 cells. In addition, this effect was mediated by the phosphatidylinositol 3-kinase-dependent pathway rather than the mitogen-activated protein kinase pathway. AdipoR1 expression in insulin-resistant diabetic mice was also investigated. AdipoR1 expression was decreased by 36% in type 2 diabetic obese db/db mice compared with lean mice. In contrast, hepatic AdipoR2 expression was not significantly changed in either STZ mice or genetically obese mice. Our results indicate that regulation of AdipoR1, but not that of AdipoR2, may be involved in glucose and lipid metabolism in diabetic states.

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