Abstract:
:A midregion fragment of PTH-related protein (PTHrP), which is intensively conserved across species, has been identified as a secretory product of several different cell types, including keratinocytes and squamous carcinomas. As recent data suggest that a midregion PTHrP fragment may be biologically active, we hypothesized that midregion PTHrPs interact with unique cell surface receptors that mediate autocrine or paracrine action. Dose-dependent transient elevations in intracellular calcium ([Ca2-]i) were observed in fura-2-loaded SqCC/Y1 squamous carcinoma cells exposed to human (h) PTHrP-(67-86)NH2, [Tyr36]hPTHrP-(1-36)NH2, and hPTHrP-(1-141) at concentrations ranging from 1 pM to 1 microM. The effects of maximal stimulatory concentrations of [Tyr36]PTHrP-(1-36)NH2 and PTHrP-(67-86)NH2 on [Ca2+]i were additive. The inhibitory PTH analog, [D-Trp12,Tyr34]bovine PTH-(7-34)NH2, attenuated the [Ca2+]i response to [Tyr36]hPTHrP-(1-36)NH2, but not that to PTHrP-(67-86)NH2. These data suggest that PTHrP-(67-86)NH2 activates a different receptor pathway in SqCC/Y1 cells from the one activated by [Tyr36]hPTHrP-(1-36)NH2. Radiolabeled PTHrP-(67-86)NH2 did not bind to SqCC/Y1 cells, and PTHrP-(67-86)NH2 did not compete for binding of 125I-labeled [Tyr36]PTHrP-(1-36)NH2 to PTH/PTHrP receptors on SaOS-2 osteosarcoma cells. Activation of the phospholipase C pathway by PTHrP-(67-86)NH2 was confirmed by exposing SqCC/Y1 cells to peptide for 1 min and measuring the accumulation of inositol trisphosphates. PTHrP-(67-86)NH2 treatment (100 nM) resulted in maximal stimulation of inositol trisphosphates of 3.1 +/- 0.1-fold over the control value, with an EC50 of 1.5 +/- 1.2 nm. In contrast, PTHrP-(67-86)NH2 (0.1 nM to 1 microM) did not stimulate adenylyl cyclase in SqCC/Y1 cells despite vigorous stimulation of cAMP formation by isoproterenol (1 microM) to 66-fold over the basal value. To determine whether messenger RNA (mRNA) prepared from SqCC/Y1 cells would direct the translation of a receptor protein that mediated a [Ca2+]i response to PTHrP-(67-86)NH2, we performed expression studies in Xenopus oocytes. Fluo-3 fluorescence in Xenopus oocytes expressing SqCC/Y1 mRNA was visualized by confocal video microscopy after exposure to 1 microM PTHrP-(67-86)NH2. Clear increases in [Ca2+]i were detected in mRNA-injected, but not in sham-injected, oocytes. Finally, we examined the effect of PTHrP-(67-86)NH2 treatment on fibronectin secretion from SqCC/YN1 cells. A significant 3.5-fold increase in fibronectin secretion into conditioned medium was observed when SqCC/Y1 cells were exposed to 100 nM PTHrP-(67-86)NH2, and this effect was dose dependent, with an EC50 of 0.1 nM. We conclude that PTHrP-(67-86)NH2 activates phospholipase C-dependent pathways in SqCC/Y1 cells through a receptor distinct from that activated by PTHrP-(1-36) in the same cells. As a midregion secretory fragment of PTHrP has been partially purified from several different cell types, this receptor may have broad biological significance.
journal_name
Endocrinologyjournal_title
Endocrinologyauthors
Orloff JJ,Ganz MB,Nathanson MH,Moyer MS,Kats Y,Mitnick M,Behal A,Gasalla-Herraiz J,Isales CMdoi
10.1210/endo.137.12.8940360subject
Has Abstractpub_date
1996-12-01 00:00:00pages
5376-85issue
12eissn
0013-7227issn
1945-7170journal_volume
137pub_type
杂志文章相关文献
ENDOCRINOLOGY文献大全abstract::Relaxin is a naturally occurring regulator of collagen turnover. In this study, we determined the role of endogenous relaxin in the pathogenesis of primary tubulointerstitial fibrosis after unilateral ureteric obstruction (UUO). Four- to 6-wk-old relaxin (RLX) gene-knockout (RLX(-/-)) and age-matched wild-type (RLX(+/...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2006-0814
更新日期:2007-02-01 00:00:00
abstract::Myocardial fibrosis is a key pathological change in a variety of heart diseases contributing to the development of heart failure, arrhythmias, and sudden death. Recent studies have shown that relaxin prevents and reverses cardiac fibrosis. Endogenous expression of relaxin was elevated in the setting of heart disease; ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2012-1114
更新日期:2012-08-01 00:00:00
abstract::We have found notable sex difference in peptidylarginine deiminase (EC 3.5.3.15) in rat pituitaries. Pituitaries collected from 3-week to 6-month-old male rats, and those from 3-week-old females showed negligible enzyme activities. The enzyme activity of female pituitaries increased markedly by 2 months, and even furt...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-124-6-2666
更新日期:1989-06-01 00:00:00
abstract::The mineralocorticoid receptor (MR) is a member of the steroid-thyroid hormone receptor superfamily of ligand-dependent transcription factors with diverse functions including the biological actions of aldosterone. Identification of the various transcriptional coregulators of MR is essential for understanding the compl...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2017-00095
更新日期:2017-07-01 00:00:00
abstract::To determine if CRH and glucocorticoids are respectively required for hypophagia and catabolism in malnutrition, we have subjected wild-type (WT) and CRH knockout (KO) mice to dietary protein deprivation. Compared with WT mice, CRH KO mice exhibited greater decreases in food intake and negligible change in plasma cort...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.140.8.6910
更新日期:1999-08-01 00:00:00
abstract::The antiestrogen ICI 164,384 (ICI) binds the estrogen receptor (ER) with approximately 20% the affinity of estradiol, but without the partial agonistic effects caused by tamoxifen. Investigations into the mechanism of ICI action have used ER molecules expressed in vitro to examine the binding of ER to ICI and the capa...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-129-4-2000
更新日期:1991-10-01 00:00:00
abstract::The binding characteristics of Sertoli Cell Factor (SCF) to the anterior pituitaries were examined using tissue homogenates and cultured cells. Tritium-labeled SCF (3H-SCF), synthesized by rat Sertoli cells in vitro in the presence of 3H-leucine and partly purified by Sephadex gel chromatography, was used to the ligan...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-111-2-696
更新日期:1982-08-01 00:00:00
abstract::Alzheimer's disease (AD) is a progressive neurodegenerative disorder whose etiology is presently unknown. Probably the most consistent and widespread deficit seen in this syndrome is that of the basal forebrain cholinergic system. We have previously demonstrated that estradiol (E2) modulates the function of these neur...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.136.5.7720680
更新日期:1995-05-01 00:00:00
abstract::IL-18 was identified due to its ability to induce interferon-gamma (IFNgamma) production by T cells. It is a pleiotropic factor that shares structural features with IL-1 and functional activities with IL-12. IL-18 has a role in T cell development, where it has been demonstrated to act cooperatively with IL-12 to regul...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2002-220936
更新日期:2003-04-01 00:00:00
abstract::The present studies demonstrate that the murine adrenocortical tumor cell line Y-1 releases a digoxin-like immunoreactive material into both serum-supplemented nutrient medium and minimal Krebs-Ringer bicarbonate medium. Release of pregnenolone into minimal medium from these cells was consistently inhibited by additio...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-125-5-2580
更新日期:1989-11-01 00:00:00
abstract::In this study we used live-cell immunocytochemistry and confocal microscopy to study the release from a single vesicle in a simplified system called membrane lawns. The lawns were prepared by exposing differentiated pituitary prolactin (PRL)-secreting cells to a hypoosmotic shear stress. The density of the immunolabel...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2012-2022
更新日期:2013-03-01 00:00:00
abstract::Using a primary culture of neonatal rat heart, we investigated the properties of iodothyronine 5'-deiodinating activity in the heart. 125I- release from [125I] reverse T3 incubated with cell homogenates depended on the concentrations of protein and dithiothreitol, pH, incubation time, and temperature of the incubation...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-128-6-3105
更新日期:1991-06-01 00:00:00
abstract::To evaluate the relative contribution of the GH/IGF axis to the development of peak bone mineral density (BMD), we measured skeletal changes in IGF-I knockout (KO), IGF-II KO, and GH-deficient lit/lit mice and their corresponding control mice at d 23 (prepubertal), 31 (pubertal), and 56 (postpubertal) in the entire fe...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2002-220948
更新日期:2003-03-01 00:00:00
abstract::The conversion of T4 to T3 in the brain and anterior pituitary gland contributes significantly to the T3 content of these tissues and appears to be an important modulator of thyroid hormone action. In the present study, the antimanic agent lithium was demonstrated in cultured neural and pituitary tissue to have a sign...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-120-4-1430
更新日期:1987-04-01 00:00:00
abstract::We investigated the contribution of corticotropin-releasing factor (CRF) receptors types 1 and 2 (CRF(1) and CRF(2)) in mediating the ACTH response to shock, alcohol injection, or endotoxemia in the rat. Peptidic (Astressin B and Astressin(2)-B) and nonpeptidic (NBI 30775) CRF antagonists were injected iv before the s...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2002-0117
更新日期:2003-06-01 00:00:00
abstract::Amphibian skin has functional characteristics of epithelium in the mammalian distal nephron and plays an important role in sodium and water metabolism in these animals. A peptide extracted from the skin of the Australian frog Crinia georgiana has been purified, has been determined to have the amino acid sequence of [A...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-122-1-359
更新日期:1988-01-01 00:00:00
abstract::Selective inhibitors of sodium glucose cotransporter-2 (SGLT2) are widely used for the treatment of type 2 diabetes and act primarily to lower blood glucose by preventing glucose reabsorption in the kidney. However, it is controversial whether these agents also act on the pancreatic islet, specifically the α cell, to ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endocr/bqaa080
更新日期:2020-08-01 00:00:00
abstract::The present study was undertaken to evaluate the efficacy of an estradiol-chemical delivery system (E2-CDS) for the brain vs. estradiol benzoate (E2-BNZ) in suppressing serum testosterone (T) and weights of the ventral prostate and seminal vesicle in male rats. Also, the role of serum T in the weight reduction of andr...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-129-2-726
更新日期:1991-08-01 00:00:00
abstract::The binding properties of the gamma-emitting 125I-labeled 11 beta-methoxy analog of 16 alpha-iodoestradiol, 11 beta-methoxy-16 alpha-iodoestradiol (MIE2), were characterized for its use in vivo as a ligand for the measurement and localization of estrogen-binding sites. In binding displacement studies, MIE2 bound to ra...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-124-5-2074
更新日期:1989-05-01 00:00:00
abstract::Immunological and binding methods have been used to demonstrate that acute inflammation induced in the pregnant mouse by a single sc turpentine injection elicits plasma protein responses in the fetal as well as in the maternal compartment. The maternal response involves, along with the classical pattern of positive an...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-120-5-1782
更新日期:1987-05-01 00:00:00
abstract::MRL-lpr/lpr mice manifest a systemic lupus-like autoimmune disease. As part of this syndrome, the mice spontaneously develop autoimmune thyroiditis, which is morphologically and biochemically similar to human autoimmune thyroiditis. In this study we investigated whether thyroid tissue obtained from sites of chronic in...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.136.8.7628400
更新日期:1995-08-01 00:00:00
abstract::We previously reported that dexamethasone (DEX) induces dose-dependent biphasic effects on steady state somatostatin (SS) messenger RNA (mRNA) levels in normal rat islet and islet SS-producing tumor cells (1027B2), characterized by stimulation at low doses and marked inhibition at high doses. The stimulatory effect is...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.136.6.7750460
更新日期:1995-06-01 00:00:00
abstract::Nuclear receptor function on DNA is regulated by the balanced recruitment of coregulatory complexes. Recruited proteins that increase gene expression are called coactivators, and those that decrease gene expression are called corepressors. Little is known about the role of corepressors, such as nuclear receptor corepr...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2009-0594
更新日期:2010-03-01 00:00:00
abstract::Pituitary homeobox 1 (Ptx1) is a homeodomain-containing transcription factor acting on transcription of all pituitary hormone genes. Its expression is first detected in the stomodeal ectoderm and is maintained in all derivatives of this structure, including Rathke's pouch. We now show that Ptx1 is expressed in all pit...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.140.3.6549
更新日期:1999-03-01 00:00:00
abstract::Explants from nonmenstrual endometria cultured in the absence of ovarian hormones undergo tissue breakdown. Addition of estradiol and progesterone (EP) prevents proteolysis. Explants include stromal and epithelial compartments which play different but complementary roles in endometrial physiology, including tissue rem...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2009-1398
更新日期:2010-09-01 00:00:00
abstract::The effect of fasting on hepatic endothelial lipase activity in the liver of adult rats was investigated. We found that, both in male and female rats, fasting produced a progressive decrease of the hepatic endothelial lipase activity. Upon refeeding, the activity returned to control values in 48 h. In isolated livers ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-129-5-2599
更新日期:1991-11-01 00:00:00
abstract::Starvation depresses thyroid gland function. In addition, the peripheral turnover of thyroxine (T4) is reduced, in part due to decreased fecal elimination of T4. The present studies were performed to determine if starvation also affects the deiodinative pathway for T4 degradation. Rats were isotopically equilibrated w...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-96-6-1525
更新日期:1975-06-01 00:00:00
abstract::In muscular dystrophy there is an imbalance between muscle protein synthesis and protein degradation, resulting in net muscle catabolism and progressive muscle weakness and wasting. Both insulin and insulin-like growth factor I (IGF-I) are known to have an anabolic effect on skeletal muscle, which is believed to be en...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.136.11.7588220
更新日期:1995-11-01 00:00:00
abstract::Using a sensitive method for the simultaneous measurement of TSH subunit mRNAs, we have investigated their hormonal regulation in the pituitary glands of normal and hypothyroid rats. Oligodeoxyribonucleotides (probes) complementary to coding regions of rat alpha- and TSH beta-subunit mRNAs were synthesized. These prob...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-117-3-1272
更新日期:1985-09-01 00:00:00
abstract::We previously examined the segregation patterns of two polymorphic restriction enzyme sites for EcoRI and HindIII in the 3'-flanking region of human CG-alpha gene in placenta and choriocarcinoma. We observed that a unique combination of restriction sites predominates in choriocarcinoma while this pattern was rare in p...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-119-5-2124
更新日期:1986-11-01 00:00:00