The In Vitro Effect of Prostaglandin E2 and F2α on the Chemerin System in the Porcine Endometrium during Gestation

Chemerin belongs to the group of adipocyte-derived hormones known as adipokines, which are responsible mainly for the control of energy homeostasis. Adipokine exerts its influence through three receptors: Chemokine-like receptor 1 (CMKLR1), G protein-coupled receptor 1 (GPR1), and C-C motif chemokine receptor-like 2 (CCRL2). A growing body of evidence indicates that chemerin participates in the regulation of the female reproductive system. According to the literature, the expression of chemerin and its receptors in reproductive structures depends on the local hormonal milieu. The aim of this study was to investigate the in vitro effect of prostaglandins E2 (PGE2) and F2α (PGF2α) on chemerin and chemerin receptor (chemerin system) mRNAs (qPCR) and proteins (ELISA, Western blotting) in endometrial tissue explants collected from early-pregnant gilts. Both PGE2 and PGF2α significantly influenced the expression of the chemerin gene, hormone secretion, and the expression of chemerin receptor genes and proteins. The influence of both prostaglandins on the expression of the chemerin system varied between different stages of gestation. This is the first study to describe the modulatory effect of PGE2 and PGF2α on the expression of the chemerin system in the porcine uterus during early gestation.

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MOLECULAR EVOLUTION OF GPCRS: 26Rfa/GPR103

Journal of Molecular Endocrinology ◽

10.1530/jme-13-0207 ◽

2014 ◽

Vol 52 (3) ◽

pp. T119-T131 ◽

Cited By ~ 24

Author(s):

Kazuyoshi Ukena ◽

Tomohiro Osugi ◽

Jérôme Leprince ◽

Hubert Vaudry ◽

Kazuyoshi Tsutsui

Keyword(s):

Energy Homeostasis ◽

Hormone Secretion ◽

Pituitary Hormone ◽

Nociceptive Transmission ◽

Functional Studies ◽

Cognate Receptor ◽

Current State ◽

Representative Species ◽

Peptide Family ◽

G Protein Coupled

Neuropeptides possessing the Arg-Phe-NH2 (RFamide) motif at their C-termini (designated as RFamide peptides) have been characterized in a variety of animals. Among these, neuropeptide 26RFa (also termed QRFP) is the latest member of the RFamide peptide family to be discovered in the hypothalamus of vertebrates. The neuropeptide 26RFa/QRFP is a 26-amino acid residue peptide that was originally identified in the frog brain. It has been shown to exert orexigenic activity in mammals and to be a ligand for the previously identified orphan G protein-coupled receptor, GPR103 (QRFPR). The cDNAs encoding 26RFa/QRFP and QRFPR have now been characterized in representative species of mammals, birds, and fish. Functional studies have shown that, in mammals, the 26RFa/QRFP–QRFPR system may regulate various functions, including food intake, energy homeostasis, bone formation, pituitary hormone secretion, steroidogenesis, nociceptive transmission, and blood pressure. Several biological actions have also been reported in birds and fish. This review summarizes the current state of identification, localization, and understanding of the functions of 26RFaQRFP and its cognate receptor, QRFPR, in vertebrates.

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In vitro effect of 4-nonylphenol on human chorionic gonadotropin (hCG) stimulated hormone secretion, cell viability and reactive oxygen species generation in mice Leydig cells

Environmental Pollution ◽

10.1016/j.envpol.2016.12.053 ◽

2017 ◽

Vol 222 ◽

pp. 219-225 ◽

Cited By ~ 18

Author(s):

Tomáš Jambor ◽

Eva Tvrdá ◽

Eva Tušimová ◽

Anton Kováčik ◽

Jana Bistáková ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Cell Viability ◽

Chorionic Gonadotropin ◽

Human Chorionic Gonadotropin ◽

Leydig Cells ◽

Hormone Secretion ◽

Reactive Oxygen Species Generation ◽

Oxygen Species ◽

Vitro Effect

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The In Vitro Effect of Leptin on Growth Hormone Secretion from Primary Cultured Ovine Somatotrophs

Endocrine ◽

10.1385/endo:14:1:073 ◽

2001 ◽

Vol 14 (1) ◽

pp. 073-078 ◽

Cited By ~ 14

Author(s):

Chen Chen ◽

Sang-Gun Roh ◽

Gui-Ying Nie ◽

Kylie Loneragan ◽

Ru-Wei Xu ◽

...

Keyword(s):

Growth Hormone ◽

Hormone Secretion ◽

Growth Hormone Secretion ◽

Vitro Effect

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Deficiency of TGR5 exacerbates immune-mediated cholestatic hepatic injury by stabilizing the β-catenin destruction complex

International Immunology ◽

10.1093/intimm/dxaa002 ◽

2020 ◽

Vol 32 (5) ◽

pp. 321-334 ◽

Cited By ~ 2

Author(s):

Jianhua Rao ◽

Chao Yang ◽

Shikun Yang ◽

Hao Lu ◽

Yuanchang Hu ◽

...

Keyword(s):

Energy Homeostasis ◽

Hepatic Injury ◽

Inflammatory Responses ◽

Therapeutic Implications ◽

Immune Mediated ◽

Duct Ligation ◽

G Protein Coupled ◽

Therapeutic Perspective

Abstract Intrahepatic cholestasis induced by drug toxicity may cause cholestatic hepatic injury (CHI) leading to liver fibrosis and cirrhosis. The G protein-coupled bile acid receptor 1 (TGR5) is a membrane receptor with well-known roles in the regulation of glucose metabolism and energy homeostasis. However, the role and mechanism of TGR5 in the context of inflammation during CHI remains unclear. Wild-type (WT) and TGR5 knockout (TGR5−/−) mice with CHI induced by bile duct ligation (BDL) were involved in vivo, and WT and TGR5−/− bone marrow-derived macrophages (BMDMs) were used in vitro. TGR5 deficiency significantly exacerbated BDL-induced liver injury, inflammatory responses and hepatic fibrosis compared with WT mice in vivo. TGR5−/− macrophages were more susceptible to lipopolysaccharide (LPS) stimulation than WT macrophages. TGR5 activation by its ligand suppressed LPS-induced pro-inflammatory responses in WT but not TGR5−/− BMDMs. Notably, expression of β-catenin was effectively inhibited by TGR5 deficiency. Furthermore, TGR5 directly interacted with Gsk3β to repress the interaction between Gsk3β and β-catenin, thus disrupting the β-catenin destruction complex. The pro-inflammatory nature of TGR5-knockout was almost abolished by lentivirus-mediated β-catenin overexpression in BMDMs. BMDM migration in vitro was accelerated under TGR5-deficient conditions or supernatant from LPS-stimulated TGR5−/− BMDMs. From a therapeutic perspective, TGR5−/− BMDM administration aggravated BDL-induced CHI, which was effectively rescued by β-catenin overexpression. Our findings reveal that TGR5 plays a crucial role as a novel regulator of immune-mediated CHI by destabilizing the β-catenin destruction complex, with therapeutic implications for the management of human CHI.

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Screening for GPR101 defects in pediatric pituitary corticotropinomas

Endocrine Related Cancer ◽

10.1530/erc-16-0091 ◽

2016 ◽

Vol 23 (5) ◽

pp. 357-365 ◽

Cited By ~ 20

Author(s):

Giampaolo Trivellin ◽

Ricardo R Correa ◽

Maria Batsis ◽

Fabio R Faucz ◽

Prashant Chittiboina ◽

...

Keyword(s):

Adrenocorticotropic Hormone ◽

Somatic Mutations ◽

Hormone Secretion ◽

Camp Signaling ◽

Pituitary Hormone ◽

Significant Percentage ◽

Functional Studies ◽

Acth Secreting ◽

G Protein Coupled

Cushing’s disease (CD) in children is caused by adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas. Germline or somatic mutations in genes such as MEN1, CDKIs, AIP, and USP8 have been identified in pediatric CD, but the genetic defects in a significant percentage of cases are still unknown. In this study, we investigated the orphan G-protein-coupled receptor GPR101, a gene known to be involved in somatotropinomas, for its possible involvement in corticotropinomas. We performed GPR101 sequencing, expression analyses by RT-qPCR and immunostaining, and functional studies (cell proliferation, pituitary hormone secretion, and cAMP measurement) in a series of patients with sporadic CD secondary to ACTH-secreting adenomas in whom we extracted DNA from peripheral blood and pituitary tumor samples (n=36). No increased GPR101 expression was observed in tumors compared with normal pituitary (NP) tissues, nor did we find a correlation between GPR101 and ACTH expression levels. Sequence analysis revealed a very rare germline heterozygous GPR101 variant (p.G31S) in one patient with CD. Overexpression of the p.G31S variant did not lead to increased growth and proliferation, although modest effects on cAMP signaling were observed. GPR101 is not overexpressed in ACTH-secreting tumors compared with NPs. In conclusion, rare germline GPR101 variant was found in one patient with CD, but in vitro studies did not support a consistent pathogenic effect. GPR101 is unlikely to be involved in the pathogenesis of CD.

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Growth hormone (GH)-releasing heptapeptide, but not GH-releasing hormone, inhibits thyrotropin-stimulated thyroid hormone secretion and cAMP formation in cultured human thyroid follicles

Acta Endocrinologica ◽

10.1530/eje.0.1330117 ◽

1995 ◽

Vol 133 (1) ◽

pp. 117-120 ◽

Cited By ~ 3

Author(s):

Z Kraiem ◽

CY Bowers ◽

E Sobel ◽

Z Laron

Keyword(s):

Growth Hormone ◽

Thyroid Hormone ◽

Medical Center ◽

Hormone Secretion ◽

Inhibitory Effect ◽

Human Thyroid ◽

Releasing Hormone ◽

Vitro Effect ◽

Camp Formation

Kraiem Z., Bowers CY, Sobel E, Laron Z. Growth hormone (GH)-releasing heptapeptide, but not GHreleasing hormone, inhibits thyrotropin-stimulated thyroid hormone secretion and cAMP formation in cultured human thyroid follicles. Eur J Endocrinol 1995;133:117–20. ISSN 0804–4643 Synthetic heptapeptide growth hormone-releasing peptide-1 (GHRP-1) potently stimulates GH release in many species, including humans. We investigated the direct in vitro effect of this peptide, compared to growth hormone-releasing hormone (GHRH), on cultured human thyroid follicles. The results indicate that whereas GHRP-1 (6–600 μg/l) or GHRH (6–600 μg/l) alone had no effect on basal triiodothyronine (T3) secretion or cAMP formation, the heptapeptide (6–600 μg/l), but not GHRH (6–1200 μg/l), dose-dependently inhibited thyrotropin (TSH)-stimulated T3 secretion and cAMP formation. Moreover, GHRP-1 also dose-dependently inhibited forskolin-stimulated T3 secretion. It would seem, therefore, that the GHRP-1-induced inhibitory effect on thyroid function is located downstream of cAMP formation, without necessarily excluding an additional inhibitory action at a pre-cAMP site. These results additionally demonstrate differences in the mode of action of GHRP-1 and GHRH. Z Kraiem, Endocrine Research Unit, Carmel Medical Center, 7 Michal Street, Haifa 34362, Israel

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Expression of Chemerin and Its Receptors in the Porcine Hypothalamus and Plasma Chemerin Levels during the Oestrous Cycle and Early Pregnancy

International Journal of Molecular Sciences ◽

10.3390/ijms20163887 ◽

2019 ◽

Vol 20 (16) ◽

pp. 3887 ◽

Cited By ~ 11

Author(s):

Nina Smolinska ◽

Marta Kiezun ◽

Kamil Dobrzyn ◽

Edyta Rytelewska ◽

Katarzyna Kisielewska ◽

...

Keyword(s):

Early Pregnancy ◽

Energy Homeostasis ◽

Preoptic Area ◽

Oestrous Cycle ◽

Mediobasal Hypothalamus ◽

Quantitative Real Time Pcr ◽

Hormone Production ◽

Fluorescent Immunohistochemistry ◽

Hormonal Milieu ◽

G Protein Coupled

Chemerin (CHEM) may act as an important link integrating energy homeostasis and reproductive functions of females, and its actions are mediated by three receptors: chemokine-like receptor 1 (CMKLR1), G protein-coupled receptor 1 (GPR1), and C-C motif chemokine receptor-like 2 (CCRL2). The aim of the current study was to compare the expression of CHEM and its receptor (CHEM system) mRNAs (quantitative real-time PCR) and proteins (Western blotting and fluorescent immunohistochemistry) in the selected areas of the porcine hypothalamus responsible for gonadotropin-releasing hormone production and secretion: the mediobasal hypothalamus, preoptic area and stalk median eminence during the oestrous cycle and early pregnancy. Moreover, plasma CHEM concentrations were determined using ELISA. The expression of CHEM system has been demonstrated in the porcine hypothalamus throughout the luteal phase and follicular phase of the oestrous cycle, and during early pregnancy from days 10 to 28. Plasma CHEM levels and concentrations of transcripts and proteins of CHEM system components in the hypothalamus fluctuated throughout pregnancy and the oestrous cycle. Our study was the first experiment to demonstrate the presence of CHEM system mRNAs and proteins in the porcine hypothalamus and the correlations between the expression levels and physiological hormonal milieu related to the oestrous cycle and early pregnancy.

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