Abstract:
:Prostaglandin (PG) E2 (PGE(2)) plays a central role in the regulation of smooth muscle contractions. Classically, PGE(2) stimulates contractions via EP1 and EP3 receptors, whereas EP2 and EP4 maintain quiescence. Labor involves a change from myometrial quiescence to contractions with a shift from anti- to proinflammatory pathways. EP2, a Gαs-coupled receptor, is known to mediate its actions via cAMP signaling. However, we have recently shown that EP2 also activates the proinflammatory PG G/H synthase-2 (PGHS-2). Here, we identify the mechanism underlying the ability of EP2 to maintain uterine quiescence and activate a proinflammatory/prolabor response in term-pregnant human myometrium. Human myometrial biopsies for in vivo and in vitro studies were taken at cesarean section at term, before or after the onset of labor. Activation of EP2 increased intracellular levels of cAMP and reduced contractility. Contrastingly, EP2 stimulation increased levels of PGHS-2, membrane-associated PGE synthase-1, and PGE(2). This was entirely dependent on EP2-mediated activation of calcium signaling. Both calcium signaling and up-regulation of PGHS-2 were insensitive to the Gαi inhibitor pertussis toxin but inhibited by small interfering RNA knockdown of Gαq/11. There were no differences in EP2 mRNA or protein levels between upper or lower segment myometrium or between pre- and postlabor myometrium. However, in myocytes taken after the onset of labor, cAMP signaling was markedly attenuated, whereas activation of calcium and PGHS-2 was preserved. Overall, the dual coupling of EP2 to Gαs-cAMP and Gαq/11-calcium pathways underlies its ability to mediate contrasting functions in term pregnancy and the "switching" to a prolabor receptor.
journal_name
Endocrinologyjournal_title
Endocrinologyauthors
Kandola MK,Sykes L,Lee YS,Johnson MR,Hanyaloglu AC,Bennett PRdoi
10.1210/en.2013-1761subject
Has Abstractpub_date
2014-02-01 00:00:00pages
605-17issue
2eissn
0013-7227issn
1945-7170pii
en.2013-1761journal_volume
155pub_type
杂志文章相关文献
ENDOCRINOLOGY文献大全abstract::Mechanisms underlying lymphocyte infiltration of the thyroid gland and orbit in Graves' disease (GD) are poorly understood. The IGF-I receptor (IGF-IR) is a newly recognized self-antigen that, when activated in GD fibroblasts by IGF-I or GD-IgGs, provokes the expression of IL-16 and RANTES (regulated upon activation, ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2005-1375
更新日期:2006-04-01 00:00:00
abstract::In the bovine ovary, thecal cells are the only cell type capable of expressing the CYP17 gene in response to LH. With the onset of ovulation and luteinization in the cow, there is complete loss of P450c17alpha expression. To characterize the molecular mechanisms involved in tissue-specific regulation of the CYP17 gene...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.138.5.5112
更新日期:1997-05-01 00:00:00
abstract::LHRH release is dependent on the availability of calcium, and prostaglandin E2 is a potent releaser of LHRH. Therefore, we investigated the role of phospholipase A2 (PLA2) on the release of LHRH from the hypothalamus. Four rat hypothalami were perifused with Krebs-Ringer buffer, and after a 60-min preincubation period...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-121-4-1483
更新日期:1987-10-01 00:00:00
abstract::Physiological roles for PTH-related peptide (PTHrP) appear varied, but remain to be clarified. The peptide is present in large amounts in milk, and PTHrP mRNA has been shown to be present in high amounts in lactating mammary gland. Because PTHrP can cause smooth muscle relaxation, we hypothesized that the peptide migh...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.133.3.8396010
更新日期:1993-09-01 00:00:00
abstract::Estradiol imprinting plays an important role in the regulation of galanin (GAL) gene expression in the rat. In the anterior pituitary gland, GAL gene expression is greatly induced by estrogen. The relative involvement that the two estrogen receptor subtypes, alpha and beta, have in regulating this induction is not kno...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.140.6.6932
更新日期:1999-06-01 00:00:00
abstract::The hepatic extractions of gastric inhibitory polypeptide (GIP) and insulin were determined using in vitro and in vivo methods to assess the role of the liver in GIP metabolism and the possible effect of GIP on the hepatic extraction of insulin. During in vitro studies using the isolated perfused rat liver, infusion o...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-115-3-1011
更新日期:1984-09-01 00:00:00
abstract::To study blood capillary growth in the hyperplastic thyroid gland, rats were fed 0.25% thiouracil in a low iodine diet for time intervals up to 100 days. Thyroids were fixed by vascular perfusion and embeded in Epon. Whole lobes were sectioned from pole to pole and slides were prepared of sections every 0.3 mm. Capill...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-103-6-2306
更新日期:1978-12-01 00:00:00
abstract::The effects of dopamine (DA) on voltage-dependent Ca2+ currents were investigated in cultured rat lactotroph cells using the patch clamp recording technique. Each recorded cell was identified by the reverse hemolytic plaque assay. In the whole-cell configuration, two types of Ca2+ currents, L and T, were characterized...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-127-3-990
更新日期:1990-09-01 00:00:00
abstract::Increasing adiposity predisposes to the development of the metabolic syndrome, in part, through adipose tissue dysregulation and inflammation. In addition, offspring nutrient-restricted (NR) in utero can exhibit an increased risk of early-onset insulin resistance and obesity, although the mechanisms remain unclear. We...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2008-1784
更新日期:2009-08-01 00:00:00
abstract::We have investigated the role of protein kinase C (PKC) isoenzymes in the differential growth regulation of human pancreatic carcinoma cell lines by all-trans retinoic acid (RA). RA treatment results in dose-dependent stimulation of anchorage-independent growth in AsPc1 cells and growth inhibition in Capan 2 cells. Bo...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.137.8.8754760
更新日期:1996-08-01 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::To examine the possibility that the prepubertal hiatus in gonadotropin secretion in primates is occasioned by an endogenous opioid peptide (EOP)-dependent suppression of pulsatile GnRH release, the ability of an EOP receptor antagonist, naloxone (NAL), to elicit GnRH release was examined indirectly in the rhesus monke...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-126-2-1036
更新日期:1990-02-01 00:00:00
abstract::The predisposition of the testis and ovary to primarily synthesize testosterone (T) and estradiol (E2), respectively, is due to gonadal-specific cell types that differentially express the various hydroxysteroid (17beta) dehydrogenase (HSD17B) isoforms. In testes, Leydig cells rely on LH stimulation to maintain express...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2006-0276
更新日期:2006-08-01 00:00:00
abstract::The endocrine-disrupting chemical bisphenol A (BPA) increases adipose tissue mass in vivo and promotes adipogenesis in vitro; however, mechanisms explaining BPA's obesogenic effect remain unknown. We investigated the effects of gestational BPA and its analog, bisphenol S (BPS), exposure on the adipogenic differentiati...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2017-00615
更新日期:2017-11-01 00:00:00
abstract::Immunohistochemical (immunoperoxidase) studies were performed on 478 sections from 97 rat pituitary glands with rabbit antisera to unconjugated human synthetic calcitonin beta-endorphin, and/or ACTH-(17--39). Calcitonin-positive cells were present in a majority of the anterior lobes studied, whereas they were present ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-106-6-1966
更新日期:1980-06-01 00:00:00
abstract::The differential regulation of neurotensin (NT), calcitonin (CT), and CT gene-related peptide (CGRP) production was studied in the clonal, rat C cell-derived, 44-2C cell line. Two experimental paradigms were used: cells were incubated with maximally effective concentrations of calcium (4.0 mM); alternatively, cells we...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-121-1-361
更新日期:1987-07-01 00:00:00
abstract::Inflammatory mediators, such as cytokines and prostaglandins, play a fundamental role in estrogen-dependent breast cancer through their ability to up-regulate aromatase expression and subsequent local production of estrogens in the breast. To study the link between estrogens and inflammation further, we examined the r...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2008-0352
更新日期:2008-12-01 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::Although lower than in brain, the type 2 PTH receptor (PTH2-R) has been shown to be expressed throughout the cardiovascular system. Tuberoinfundibular peptide (TIP) purified from brain is thought to be the endogenous selective ligand of the PTH2-R. In the present studies, TIP and PTH2-R mRNA expressions were evidenced...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.143.8.8960
更新日期:2002-08-01 00:00:00
abstract::The mechanisms by which bacterial endotoxin [lipopolysaccharide (LPS)] stimulates the hypothalamo-pituitary-adrenal axis (HPAA) have not been elucidated. The present study was designed to investigate the involvement of macrophages in plasma ACTH and corticosterone responses to LPS administration in rats using selectiv...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-129-1-330
更新日期:1991-07-01 00:00:00
abstract::Tumor necrosis factor-alpha (TNF alpha), a product of activated monocytes, induces tissue wasting in certain solid tumors in vivo and in in vitro model systems. Recent studies indicate that TNF alpha also regulates cell replication and expression of differentiated function in a variety of nonneoplastic cell systems. S...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-123-3-1442
更新日期:1988-09-01 00:00:00
abstract::The intermediary role of the putative inhibitory regulatory membrane protein "Ni" in the "antigonadal" activity of the neurohypophysial hormones was investigated in vitro with the use of a primary culture of rat testicular cells. To this end, use was made of the pertussis toxin (PT) probe, an exotoxin of Bordetella pe...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-115-2-839
更新日期:1984-08-01 00:00:00
abstract::Dysregulation of the hypothalamic-pituitary-adrenocortical axis has been theoretically linked to the processes of aging for decades. To investigate the effects of age on high frequency rhythms of plasma ACTH at the time of circadian activation, integrated 2-min blood samples were collected over 4 h in 10 young and 14 ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.133.2.8393770
更新日期:1993-08-01 00:00:00
abstract::Circadian clocks have been described in each tissue of the hypothalamo-pituitary-ovarian axis. Although a role for the clock in the timing of ovulation is indicated, the impact of diseases that disrupt fertility on clock function or the clocks' role in the etiology of these pathologies has yet to be fully appreciated....
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2012-2066
更新日期:2013-04-01 00:00:00
abstract::The photoreactive analogs of vasopressin, [Phe2,Phe-(p-N3)3]AVP (3a) and [Phe-(p-N3)2]AVP (2a), and the chemically reactive analogs of vasopressin, [Phe2,Phe-(p-NHCOCH2Br)3]AVP (3b) and [Phe-(p-NHCOCH2Br)2]AVP (2c), have been tested in the toad bladder for irreversible stimulation or inhibition of the water permeabili...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-113-4-1413
更新日期:1983-10-01 00:00:00
abstract::We previously described significant differences in maximal testosterone production by Leydig cells from the following strains of inbred mice: C57BL/10J, C57BL/6J, DBA/2J, and C3H/HeJ. To evaluate whether these differences in maximal testosterone production related to the activities of the steroidogenic enzymes of the ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-115-4-1500
更新日期:1984-10-01 00:00:00
abstract::In the mouse, there is a large family of paralogous genes closely related to PRL. The objective of this report was to investigate the organization of the mouse PRL gene family locus. PRL family genes reside on chromosome 13 of the mouse genome. The PRL gene family members were localized to a series of overlapping bact...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2002-220724
更新日期:2003-01-01 00:00:00
abstract::Our laboratory has previously reported that physiological levels of progestins stimulate growth of the human breast cancer cell line T47D. We have also determined that the antiprogestin RU486 inhibits this stimulation. Here we present the unexpected finding that RU486 alone also stimulates growth of these breast cance...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-124-5-2642
更新日期:1989-05-01 00:00:00
abstract::The master circadian clock located within the hypothalamic suprachiasmatic nucleus (SCN) is necessary for the circadian rhythm of glucocorticoid (GC) release. The pathways by which the SCN sustains rhythmic GC release remain unclear. We studied the circadian regulation of cortisol release in the behaviorally split gol...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2011-1624
更新日期:2012-02-01 00:00:00
abstract::Osteoclast precursors have not been well characterized because there are no known markers that can detect them. We have used osteoclast-like cells formed in vitro to develop a panel of specific antibodies that react with mature osteoclasts, osteoclast precursors, and other cells in the osteoclast lineage. Monoclonal a...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-125-2-630
更新日期:1989-08-01 00:00:00