A novel target proposal in endometriosis: Phoenixin

The newly discovered neuropeptide "Phoenixin" might be used as a diagnostic marker

Key Points

Highlight

• Levels of "Phoenixin (PNX)" combined with LH/FSH ratio might be used to differentiate foci of ectopic endometrium, therefore, posing as a novel diagnostic method.

Importance

• The neuropeptide PNX which takes part in the hypothalamic-pituitary-gonadal axis has been proven to have important effects on the menstrual cycle and hormonal balance.
• Its significantly lower serum levels in endometriosis patients might be useful in the diagnosis.

What's done here

• In this research study, the authors aimed to evaluate the levels of PNX, LH, FSH, 17-β estradiol, and the expression of PNX and its receptor in patients with ovarian endometriosis and compare to eutopic endometrium.
• The serum levels of PNX, LH, FSH, and 17-β estradiol were calculated using ELISA, and the expression of the precursor proteins by PCR and immunostain.

Key results

• PNX levels were significantly lower; LH/FSH ratio and the levels of 17-β estradiol were significantly higher in women with endometriosis. 
• The individual LH and FSH levels did not differ.
• The immunohistochemical staining intensity of PNX, SMIM20, and GPR173 was the same in eutopic and ectopic endometrium.

Lay Summary

As well as being a hormone-dependent reproductive system disorder, endometriosis is known to be multifactorial, which makes its etiopathogenetic mechanisms even harder to understand. Many new targets have been vastly evaluated with the hope of finding a new diagnostic test and developing alternative and better treatment methods.

A new neuropeptide secreted from the anterior hypothalamus called Phoenixin (PNX) was recently brought to light with its effects on regulating the hypothalamic-pituitary-gonadal (HPG) axis, reproductivity, cardiac health, nutrition, memory, pain, and anxiety. PNX has been shown to play a role in the menstrual cycle by inducing ovarian follicle maturation and directly affecting the HPG axis by increasing hormones such as GnRH, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). It acts through the G-protein-coupled receptor 173 (GPR173), and its precursor. Some studies have proven its aforementioned effects, however, its role was never studied in endometriosis. Molecular interactions between GnRH receptors and PNX signaling in the HPG axis were also identified in studies done on female rats.

Kulinska et al. from Poland performed a study that aimed to assess the levels of PNX, LH, FSH, 17-β estradiol, and the expression of SMIM20 via GPR173 in patients with ovarian endometriosis and compared the results with healthy individuals. The article was published in the October 2021 issue of the journal Biomedicines. 

In the endometriosis group, the serum PNX level was significantly lower. Even though individual LH and FSH levels did not differ, the LH/FSH ratio and the levels of 17-β estradiol were also statistically significantly higher in women with endometriosis. No difference was observed regarding the SMIM20 expression detected by real-time PCR; however, GPR173 expression was significantly lower.

The authors suggest that PNX takes part in endometriosis pathogenesis, and its reduced levels might be responsible for severe pain and hormonal imbalance. They state that a model including PNX levels and LH/FSH ratio has a very high confidence level and accuracy in determining patients with endometriosis and could be used as a diagnostic method.

Research Source: https://pubmed.ncbi.nlm.nih.gov/34680544/