Phoenixin as a New Target in the Development of Strategies for Endometriosis Diagnosis and Treatment

Small integral membrane protein 20/phoenixin (SMIM20/PNX) and its receptor GPR173 (G Protein-Coupled Receptor 173) play a role in the regulation of the hypothalamic–pituitary–gonadal axis (HPG). The aim of the study was to determine PNX, FSH, LH, and 17β-estradiol association in women with endometriosis, and the expression of SMIM20/PNX signaling via GPR173. Serum PNX, FSH, LH, and 17β-estradiol concentrations were measured by enzyme and electrochemiluminescence immunoassay. SMIM20/PNX and GPR173 expression in the eutopic and ectopic endometrium was assessed by qPCR and immunohistochemistry. Reduced PNX level, increased LH/FSH ratio and elevated 17β-estradiol concentration were found in patients with endometriosis. No differences in SMIM20 expression were observed between the studied endometria. GPR173 expression was lower in ectopic than in eutopic endometria. SMIM20 expression was mainly restricted to stroma. GPR173 was detected in some eutopic and ectopic stromal cells and in eutopic glandular epithelial cells. Discriminant analysis indicates the diagnostic relevance of PNX and LH/FSH ratio in patients with endometriosis. In women with endometriosis, reduced PNX levels and GPR173 expression may be responsible for HPG axis dysregulation. These new insights may contribute to a better understanding of the pathophysiology of endometriosis and provide the basis for a new strategy for diagnosis and treatment of endometriosis.

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17β-estradiol and ureteral contractility: A role for the G protein-coupled estrogen receptor

European Journal of Pharmacology ◽

10.1016/j.ejphar.2021.174024 ◽

2021 ◽

pp. 174024

Author(s):

Iris Lim ◽

Caio Christiansen ◽

Russ Chess-Williams

Keyword(s):

Estrogen Receptor ◽

G Protein ◽

17Β Estradiol ◽

G Protein Coupled

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17β-Estradiol at Low Concentrations Acts through Distinct Pathways in Normal Versus Benign Prostatic Hyperplasia-Derived Prostate Stromal Cells

Yearbook of Endocrinology ◽

10.1016/s0084-3741(09)79426-0 ◽

2010 ◽

Vol 2010 ◽

pp. 316-317

Author(s):

A.W. Meikle

Keyword(s):

Benign Prostatic Hyperplasia ◽

Stromal Cells ◽

Prostatic Hyperplasia ◽

Low Concentrations ◽

17Β Estradiol

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Binding of Androgen- and Estrogen-Like Flavonoids to Their Cognate (Non)Nuclear Receptors: A Comparison by Computational Prediction

Molecules ◽

10.3390/molecules26061613 ◽

2021 ◽

Vol 26 (6) ◽

pp. 1613

Author(s):

Giulia D’Arrigo ◽

Eleonora Gianquinto ◽

Giulia Rossetti ◽

Gabriele Cruciani ◽

Stefano Lorenzetti ◽

...

Keyword(s):

Nuclear Receptors ◽

Fruits And Vegetables ◽

Computational Prediction ◽

Membrane Receptors ◽

Computational Docking ◽

Docking Simulations ◽

Mediated Effects ◽

17Β Estradiol ◽

G Protein Coupled ◽

Relevant Degree

Flavonoids are plant bioactives that are recognized as hormone-like polyphenols because of their similarity to the endogenous sex steroids 17β-estradiol and testosterone, and to their estrogen- and androgen-like activity. Most efforts to verify flavonoid binding to nuclear receptors (NRs) and explain their action have been focused on ERα, while less attention has been paid to other nuclear and non-nuclear membrane androgen and estrogen receptors. Here, we investigate six flavonoids (apigenin, genistein, luteolin, naringenin, quercetin, and resveratrol) that are widely present in fruits and vegetables, and often used as replacement therapy in menopause. We performed comparative computational docking simulations to predict their capability of binding nuclear receptors ERα, ERβ, ERRβ, ERRγ, androgen receptor (AR), and its variant ART877A and membrane receptors for androgens, i.e., ZIP9, GPRC6A, OXER1, TRPM8, and estrogens, i.e., G Protein-Coupled Estrogen Receptor (GPER). In agreement with data reported in literature, our results suggest that these flavonoids show a relevant degree of complementarity with both estrogen and androgen NR binding sites, likely triggering genomic-mediated effects. It is noteworthy that reliable protein–ligand complexes and estimated interaction energies were also obtained for some suggested estrogen and androgen membrane receptors, indicating that flavonoids could also exert non-genomic actions. Further investigations are needed to clarify flavonoid multiple genomic and non-genomic effects. Caution in their administration could be necessary, until the safe assumption of these natural molecules that are largely present in food is assured.

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Protease-activated receptor signalling by coagulation proteases in endothelial cells

Thrombosis and Haemostasis ◽

10.1160/th14-02-0167 ◽

2014 ◽

Vol 112 (11) ◽

pp. 876-882 ◽

Cited By ~ 51

Author(s):

Alireza Rezaie

Keyword(s):

Endothelial Cells ◽

Vascular System ◽

Activated Protein C ◽

Integral Membrane Protein ◽

Protease Activated Receptors ◽

System A ◽

Signalling Network ◽

Protein Receptors ◽

Activate Cell ◽

G Protein Coupled

SummaryEndothelial cells express several types of integral membrane protein receptors, which upon interaction and activation by their specific ligands, initiate a signalling network that links extracellular cues in circulation to various biological processes within a plethora of cells in the vascular system. A small family of G-protein coupled receptors, termed protease-activated receptors (PAR1–4), can be specifically activated by coagulation proteases, thereby modulating a diverse array of cellular activities under various pathophysiological conditions. Thrombin and all vitamin K-dependent coagulation proteases, with the exception of factor IXa for which no PAR signalling has been attributed, can selectively activate cell surface PARs on the vasculature. Thrombin can activate PAR1, PAR3 and PAR4, but not PAR2 which can be specifically activated by factors VIIa and Xa. The mechanistic details of the specificity of PAR signalling by coagulation proteases are the subject of extensive investigation by many research groups worldwide. However, analysis of PAR signalling data in the literature has proved to be challenging since a single coagulation protease can elicit different signalling responses through activation of the same PAR receptor in endothelial cells. This article is focused on briefly reviewing the literature with respect to determinants of the specificity of PAR signalling by coagulation proteases with special emphasis on the mechanism of PAR1 signalling by thrombin and activated protein C in endothelial cells.

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Inhibition of METTL3/m6A/miR126 promotes the migration and invasion of endometrial stromal cells in endometriosis

Biology of Reproduction ◽

10.1093/biolre/ioab152 ◽

2021 ◽

Author(s):

Xiaoou Li ◽

Wenqian Xiong ◽

Xuefeng Long ◽

Xin Dai ◽

Yuan Peng ◽

...

Keyword(s):

Stromal Cells ◽

Therapeutic Target ◽

Molecular Mechanisms ◽

Cellular Migration ◽

Migration And Invasion ◽

Diagnostic Biomarker ◽

Rna Modifications ◽

Normal Endometrium ◽

Endometrial Stromal Cells ◽

Ectopic Endometrium

Abstract N6-methyladenosine (m6A), one of the most abundant RNA modifications, is involved in the progression of many diseases, but its role and related molecular mechanisms in endometriosis remain unknown. To address these issues, we detected m6A levels in normal, eutopic and ectopic endometrium and found the m6A levels decreased in eutopic and ectopic endometrium compared with normal endometrium. In addition, we proved that methyltransferase-like 3 (METTL3) downregulation accounted for m6A reduction in endometriosis. Furthermore, we observed that METTL3 knockdown facilitated the migration and invasion of human endometrial stromal cells (HESCs), while METTL3 overexpression exerted opposite effects, suggesting that METTL3 downregulation might contribute to endometriosis development by enhancing cellular migration and invasion. Mechanistically, METTL3-dependent m6A was involved in the DGCR8-mediated maturation of primary microRNA126 (miR126, pri-miR126). Moreover, miR126 inhibitor significantly enhanced the migration and invasion of METTL3-overexpressing HESCs, whereas miR126 mimics attenuated the migration and invasion of METTL3-silenced HESCs. Our study revealed the METTL3/m6A/miR126 pathway, whose inhibition might contribute to endometriosis development by enhancing cellular migration and invasion. It also showed that METTL3 might be a novel diagnostic biomarker and therapeutic target for endometriosis.

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A New Strategy for Asymmetric Synthesis Exploiting Oxime Ethers and Application to Enantioselective Syntheses of G-Protein-Coupled Receptor Ligands

19th International Congress on Heterocyclic Chemistry ◽

10.1016/b978-0-08-044304-1.50106-4 ◽

2003 ◽

pp. 114

Author(s):

Masakazu Atobe ◽

Naoki Yamazaki ◽

Chihiro Kibayashi

Keyword(s):

Asymmetric Synthesis ◽

G Protein ◽

Receptor Ligands ◽

G Protein Coupled Receptor ◽

New Strategy ◽

G Protein Coupled ◽

Enantioselective Syntheses

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17. New Strategy of Diagnosis and Treatment of Acute Aortic Dissection

Nihon Naika Gakkai Zasshi ◽

10.2169/naika.104.127b ◽

2015 ◽

Vol 104 (Suppl) ◽

pp. 127b-127b

Author(s):

Hideaki Yoshino

Keyword(s):

Aortic Dissection ◽

Acute Aortic Dissection ◽

Diagnosis And Treatment ◽

New Strategy

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Sex steroids regulate skin pigmentation through nonclassical membrane-bound receptors

eLife ◽

10.7554/elife.15104 ◽

2016 ◽

Vol 5 ◽

Cited By ~ 46

Author(s):

Christopher A Natale ◽

Elizabeth K Duperret ◽

Junqian Zhang ◽

Rochelle Sadeghi ◽

Ankit Dahal ◽

...

Keyword(s):

Hormone Receptors ◽

Treatment Options ◽

Skin Pigmentation ◽

Progesterone Receptors ◽

Steroid Hormone Receptors ◽

Pigment Synthesis ◽

17Β Estradiol ◽

Membrane Bound ◽

Epidermal Melanocyte ◽

G Protein Coupled

The association between pregnancy and altered cutaneous pigmentation has been documented for over two millennia, suggesting that sex hormones play a role in regulating epidermal melanocyte (MC) homeostasis. Here we show that physiologic estrogen (17β-estradiol) and progesterone reciprocally regulate melanin synthesis. This is intriguing given that we also show that normal primary human MCs lack classical estrogen or progesterone receptors (ER or PR). Utilizing both genetic and pharmacologic approaches, we establish that sex steroid effects on human pigment synthesis are mediated by the membrane-bound, steroid hormone receptors G protein-coupled estrogen receptor (GPER), and progestin and adipoQ receptor 7 (PAQR7). Activity of these receptors was activated or inhibited by synthetic estrogen or progesterone analogs that do not bind to ER or PR. As safe and effective treatment options for skin pigmentation disorders are limited, these specific GPER and PAQR7 ligands may represent a novel class of therapeutics.

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