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

Karolina Iwona Kulinska,Ewa Nowak-Markwitz,Krzysztof Szymanowski,Mirosław Andrusiewicz,Marek Skrzypski,Małgorzata Kotwicka,Maria Wołuń-Cholewa,Anna Dera-Szymanowska,Maria Billert

doi:10.3390/biomedicines9101427

Karolina Iwona Kulinska, Ewa Nowak-Markwitz + Show 7 more

Open Access

https://doi.org/10.3390/biomedicines9101427

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Abstract

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.

Highlights

IntroductionEndometriosis is one of the most common benign gynecological disorders
An investigation of PNX in the proper functioning of the hypothalamic–pituitary–gonadal axis (HPG) axis was initiated by Yosten et al in 2013 [7]
Further studies have shown administration of PNX-14 or PNX-20 increases the release of GnRH due to a regulatory effect on the GnRH receptor (GnRH-R)

Summary

Introduction

Endometriosis is one of the most common benign gynecological disorders. It is defined as the presence of stroma and glandular cells of the endometrium outside the uterine cavity [1]. It affects approximately 6–10% of women of reproductive age, increasing to. The most widely accepted theory of its formation is Sampson’s transplantation, and implantation theory, published a century ago. According to this theory, endometriosis results from retrograde menstrual reflux of endometrial fragments into the peritoneal cavity [3,4].

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