scholarly journals CRH Acts on CRH-R1 and -R2 to Differentially Modulate the Expression of Large-Conductance Calcium-Activated Potassium Channels in Human Pregnant Myometrium

Endocrinology ◽  
2011 ◽  
Vol 152 (11) ◽  
pp. 4406-4417 ◽  
Author(s):  
Chen Xu ◽  
Lu Gao ◽  
Xingji You ◽  
Ling Dai ◽  
Yuan Li ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Receptor Type ◽  
Uterine Contractility ◽  
Myometrial Cells ◽  
Calcium Activated Potassium Channels ◽  
Spontaneous Contractions ◽  
Crh Receptor Type 1 ◽  
Interfering Rna

CRH has been implicated to play a key role in the control of human pregnancy and parturition. Large-conductance potassium channels (BKCa) play a pivotal role in the modulation of uterine contractility during pregnancy. The objectives of the present study were to investigate the effect of CRH on BKCa expression in human pregnant myometrial cells. Myometrial tissues were collected at cesarean section from pregnant women not-in-labor (TNL) or in-labor (TL) at term, and myocytes were isolated and cultured. CRH was identified in human pregnant myometrium and mainly expressed in myometrial myocytes. Cultured myometrial cells were able to secrete CRH. In TNL myometrial cells, CRH treatment increased the expression of BKCa α- and β-subunits. CRH receptor type 1 (CRH-R1) antagonist, antalarmin, decreased whereas CRH receptor type 2 (CRH-R2) antagonist, astressin2b, increased the expression of BKCa. CRH-R2 small interfering RNA (siRNA) caused an increase, but CRH-R1 siRNA resulted in a decrease, in BKCa expression. In contrast to TNL cells, CRH exhibited an opposite effect on BKCa expression in TL myometrial cells, i.e. decreased BKCa expression. Antalarmin enhanced but astressin2b reduced BKCa expression. CRH-R2 siRNA decreased whereas CRH-R1 siRNA increased BKCa expression. 1,3-Dihydro-1-[2-hydroxy-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-2H-benzimidazol-2-one significantly inhibited the frequency of spontaneous contractions of myometrial strips, and this effect was significantly decreased in TL strips compared with TNL ones. Our data suggest that CRH-R1 and CRH-R2 show differential regulation of BKCa expression. These effects mediated by CRH-R1 and CRH-R2 are changed after the onset of labor. This leads us to suggest that CRH may fine-tune myometrial contractility by modulating the expression of BKCa during pregnancy and labor.

scholarly journals Regulation of Estradiol and Progesterone Production by CRH-R1 and -R2 Is through Divergent Signaling Pathways in Cultured Human Placental Trophoblasts

Endocrinology ◽  
2012 ◽  
Vol 153 (10) ◽  
pp. 4918-4928 ◽  
Author(s):  
Lu Gao ◽  
Yi Tao ◽  
Tianxiao Hu ◽  
Weina Liu ◽  
Chen Xu ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Phospholipase C ◽  
Culture Media ◽  
Receptor Type ◽  
Kinase C ◽  
Protein Kinase C Inhibitor ◽  
Crh Receptor Type 1 ◽  
Gαi Protein

Abstract CRH and its related peptides urocortins (UCN) have been identified in placenta and implicated to play pivotal roles in the regulation of pregnancy and parturition in humans. The objectives of present study were to investigate the effects of endogenous CRH and its related peptides in the regulation of steroid production in placenta. Placental trophoblasts were isolated from term placenta tissues and cultured for 72 h. Estradiol (E2) and progesterone (P4) contents in culture media were determined by radioimmunoassay. Treatment of cultured trophoblasts with CRH or UCNI antibody showed decreased E2, whereas increased P4 production. Treatment of cells with CRH receptor type 1 antagonist antalarmin or CRH receptor type 2 (CRH-R2) antagonist astressin-2b also decreased E2 but increased P4 production. Knockdown of CRH receptor type 1 or CRH-R2 cells showed a decrease in E2 production and an increase in P4 production. In CRH-R2 knockdown cells, CRH stimulated GTP-bound Gαs protein and phosphorylated phospholipase C-β3. Adenylyl cyclase and protein kinase A inhibitors blocked CRH-induced increased E2 production but not decreased P4 production. PLC inhibitor U73122 and protein kinase C inhibitor chelerythrine blocked the effects of CRH on E2 and P4 production in CRH-R2 knockdown cells. UCNIII, the specific CRH-R2 agonist, stimulated GTP-bound Gαi protein and phosphorylated phospholipase C-β3 expression. Both U73122 and chelerythrine blocked UCNIII-induced increased E2 production and decreased P4 production. We suggest that CRH and its related peptides might be involved in changes in the progesterone to estrogen ratio during human pregnancy.

scholarly journals Regulation des Angstverhaltens — zur Rolle neuronaler Netzwerke

BIOspektrum ◽  
2019 ◽  
Vol 25 (7) ◽  
pp. 711-714
Author(s):  
Nina Dedic ◽  
Jan M. Deussing
Keyword(s):  
Stress Response ◽  
Ventral Tegmental Area ◽  
Long Range ◽  
Dopamine Release ◽  
Receptor Type ◽  
Projection Neurons ◽  
Neuronal Circuit ◽  
Brain Reward ◽  
Crh Receptor Type 1

AbstractThe corticotropin-releasing hormone (CRH) system orchestrates the organism’s stress response including the regulation of adaptive be haviours. Here we describe a novel neuronal circuit, which acts anxiety suppressing and positively modulates dopamine release. This anxiolytic circuit comprises inhibitory CRH-expressing, long-range projection neurons within the extended amygdala. These neurons innervate the ventral tegmental area, a prominent brain reward center that expresses high levels of CRH receptor type 1.

scholarly journals Orexin A Enhances Pro-Opiomelanocortin Transcription Regulated by BMP-4 in Mouse Corticotrope AtT20 Cells

2021 ◽  
Vol 22 (9) ◽  
pp. 4553
Author(s):  
Satoshi Fujisawa ◽  
Motoshi Komatsubara ◽  
Naoko Tsukamoto-Yamauchi ◽  
Nahoko Iwata ◽  
Takahiro Nada ◽  
...  
Keyword(s):  
Stress Responses ◽  
Endocrine Function ◽  
Type I ◽  
Orexin A ◽  
Protein Levels ◽  
Bmp Receptors ◽  
Morphogenetic Protein ◽  
Crh Receptor Type 1

Orexin is expressed mainly in the hypothalamus and is known to activate the hypothalamic–pituitary–adrenal (HPA) axis that is involved in various stress responses and its resilience. However, the effects of orexin on the endocrine function of pituitary corticotrope cells remain unclear. In this study, we investigated the roles of orexin A in pro-opiomelanocortin (POMC) transcription using mouse corticotrope AtT20 cells, focusing on the bone morphogenetic protein (BMP) system expressed in the pituitary. Regarding the receptors for orexin, type 2 (OXR2) rather than type 1 (OX1R) receptor mRNA was predominantly expressed in AtT20 cells. It was found that orexin A treatment enhanced POMC expression, induced by corticotropin-releasing hormone (CRH) stimulation through upregulation of CRH receptor type-1 (CRHR1). Orexin A had no direct effect on the POMC transcription suppressed by BMP-4 treatment, whereas it suppressed Smad1/5/9 phosphorylation and Id-1 mRNA expression induced by BMP-4. It was further revealed that orexin A had no significant effect on the expression levels of type I and II BMP receptors but upregulated inhibitory Smad6/7 mRNA and protein levels in AtT20 cells. The results demonstrated that orexin A upregulated CRHR signaling and downregulated BMP-Smad signaling, leading to an enhancement of POMC transcription by corticotrope cells.

scholarly journals Cannabinoids in health and disease: pharmacological potential in metabolic syndrome and neuroinflammation

2018 ◽  
Vol 36 (2) ◽  
Author(s):  
Andrea Mastinu ◽  
Marika Premoli ◽  
Giulia Ferrari-Toninelli ◽  
Simone Tambaro ◽  
Giuseppina Maccarinelli ◽  
...  
Keyword(s):  
Cannabis Sativa ◽  
Cannabinoid Receptor ◽  
Receptor Type ◽  
History Of ◽  
Health And Disease ◽  
Pharmacological Potential ◽  
The Brain ◽  
Synthesis And Degradation

Abstract The use of different natural and/or synthetic preparations of Cannabis sativa is associated with therapeutic strategies for many diseases. Indeed, thanks to the widespread diffusion of the cannabinoidergic system in the brain and in the peripheral districts, its stimulation, or inhibition, regulates many pathophysiological phenomena. In particular, central activation of the cannabinoidergic system modulates the limbic and mesolimbic response which leads to food craving. Moreover, cannabinoid agonists are able to reduce inflammatory response. In this review a brief history of cannabinoids and the protagonists of the endocannabinoidergic system, i.e. synthesis and degradation enzymes and main receptors, will be described. Furthermore, the pharmacological effects of cannabinoids will be outlined. An overview of the involvement of the endocannabinoidergic system in neuroinflammatory and metabolic pathologies will be made. Finally, particular attention will also be given to the new pharmacological entities acting on the two main receptors, cannabinoid receptor type 1 (CB1) and cannabinoid receptor type 2 (CB2), with particular focus on the neuroinflammatory and metabolic mechanisms involved.

scholarly journals Rat TRH Receptor Type 2 Exhibits Higher Basal Signaling Activity than TRH Receptor Type 1

Endocrinology ◽  
1999 ◽  
Vol 140 (10) ◽  
pp. 4916-4919 ◽  
Author(s):  
Wei Wang ◽  
Marvin C. Gershengorn
Keyword(s):  
Receptor Type ◽  
Trh Receptor ◽  
Signaling Activity

Structural domains determining signalling characteristics of the CRH-receptor type 1 variant R1β and response to PKC phosphorylation

2008 ◽  
Vol 20 (1) ◽  
pp. 40-49 ◽  
Author(s):  
Thalia Teli ◽  
Danijela Markovic ◽  
Margaret E. Hewitt ◽  
Michael A. Levine ◽  
Edward W. Hillhouse ◽  
...  
Keyword(s):  
Receptor Type ◽  
Structural Domains ◽  
Crh Receptor Type 1

Modulation of adiponectin system expression in the porcine uterus during early pregnancy by prostaglandin E2 and F2α

2017 ◽  
Vol 29 (9) ◽  
pp. 1832 ◽  
Author(s):  
Kamil Dobrzyn ◽  
Nina Smolinska ◽  
Karol Szeszko ◽  
Marta Kiezun ◽  
Anna Maleszka ◽  
...  
Keyword(s):  
Early Pregnancy ◽  
Oestrous Cycle ◽  
Receptor Type ◽  
Adiponectin Receptor ◽  
Pcr Method ◽  
Pg E2 ◽  
Dose Dependent

Studies have demonstrated that adiponectin could be a link between reproductive functions and energy metabolism in animals. The aim of the present study was to investigate the effects of prostaglandin (PG) E2 and PGF2α (10, 50, 100, 250 and 500 ng mL–1) on the expression and secretion of adiponectin and its receptor genes and proteins by cultured in vitro porcine endometrial and myometrial tissues on Days 10–28 of pregnancy and Days 10–11 of the oestrous cycle. The gene expression was analysed using the real-time PCR method. Adiponectin protein secretion was determined by ELISA, whereas the receptors proteins content was defined using Western Blot analysis. Both PGE2 and PGF2α modulated the expression of adiponectin system genes and proteins in the uterus during early pregnancy. PGE2 and PGF2α had similar effects on the adiponectin system, which differed between the stages of gestation and between pregnancy and the oestrous cycle. On Days 10–11 of gestation, PGE2 and PGF2α generally increased adiponectin secretion by endometrial and myometrial tissues. Both PGs decreased levels of endometrial adiponectin receptor type 1 (AdipoR1), whereas only PGF2α decreased myometrial levels of AdipoR1. Both PGs increased myometrial adiponectin receptor type 2 (AdipoR2) levels. On Days 12–13 of gestation, PGE2 decreased AdipoR1 concentrations in both tissues and AdipoR2 levels in the endometrium. PGF2α decreased myometrial concentrations of both receptors. On Days 15–16 of gestation, both PGE2 and PGF2α increased concentrations of AdipoR1 and AdipoR2 in the endometrium and myometrium. PGE2 stimulated the secretion of adiponectin in the endometrium, but not in the myometrium. On Days 27–28 of pregnancy, both PGE2 and PGF2α inhibited the expression of AdipoR1 and AdipoR2 in endometrial and myometrial tissues and decreased the secretion of endometrial adiponectin. Both PGE2 and PGF2α had tissue-specific and dose-dependent effects on the adiponectin system.

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