Prolactin receptor antibodies: A novel treatment proposal for endometriosis

Study suggests prolactin receptor antibodies may be used as a novel therapeutic agent in endometriosis patients

Key Points

Highlight:

• Studies on new therapeutic agents have been increasing, which gives hope for better management of endometriosis and its symptoms. 

Importance:

• The hormonal and non-hormonal treatment options for endometriosis all have some side effects that affect patients' quality of life.
• It has previously been shown that endometriosis patients are under the effect of systemic and local hyperprolactinemia.
• Even though agents such as dopamine receptor agonists are useful in reducing prolactin levels, they cannot block all production.

What's done here:

• This is an experimental study performed on mice endometriosis models to evaluate the efficacy of Prolactin Receptor (PRLR) blocking antibodies compared to other therapeutic agents in use.
• The prolactin levels were increased to induce and accelerate the development of the lesions by increasing prolactin levels with dopamine antagonists and grafting the pituitary gland.
• The severity of the disease was assessed histopathologically.
• The mice were then treated with prolactin antibodies.

Key results

• The application of PRLR blocking antibodies inhibited endometriosis development to the same extent as anti-estrogenic drugs.
• The PRLR blocking antibodies completely inhibit prolactin secretion from all sources in contrast to the dopamine receptor agonists, which only reduces the prolactin that is caused by the increased pituitary secretion.
• PRLR blocking antibodies were found to be more tolerable making them a novel treatment option.

Lay Summary

Prolactin, a hormone that also acts as a proinflammatory cytokine through its receptor PRLR has been shown to be involved in endometriosis pathogenesis. Previous studies reported that women suffering from endometriosis had elevated prolactin levels. Also, in experimental studies done on mice, the drugs used to lower prolactin levels, such as dopamine receptor agonists, have succeeded in reducing the endometriotic lesion burden.

Otto et al. from Germany have performed an experimental study on murine endometriosis models targeted to evaluate the effects of two different PRLR blocking antibodies and compare them with several other antihormonal drugs in use. The study was published in the February 2022 issue of the journal Pharmacology Research & Perspectives.

The mice used in the experiments are known to develop endometriosis spontaneously. The prolactin levels were increased to induce and accelerate the development of the lesions by increasing prolactin levels with dopamine antagonists and grafting the pituitary gland. These mice have then treated with prolactin receptor-blocking antibodies.   

The effects of the two different PRLR blocking antibodies that researchers previously characterized were compared to danazol (an androgenic progestin), cetrorelix (a GnRH antagonist), and feslodex (an estrogen receptor antagonist). The disease severity was evaluated histopathologically based on the depth of endometrial invasion into the myometrial layer under a six-level scoring system.

It was observed that the application of PRLR blocking antibodies inhibited endometriosis development to the same extent as anti-estrogenic drugs. The authors then touched on the issue that in endometriosis, systemic hyperprolactinemia is seen with local PRLR-mediated signaling, and prolactin and its receptor were found to be upregulated in previous studies. Therefore, the dopamine receptor agonists only reduce the prolactin that is caused by the increased pituitary secretion, whereas the PRLR blocking antibodies completely inhibit prolactin secretion from all sources. What is more, PRLR antibodies are thought to be superior to dopamine receptor agonists in terms of tolerability. The study also demonstrated that PRLR antibodies did not reduce the uterine weight in contrast to anti-estrogenic compounds which proves their lack of anti-estrogenic effects. 

The authors declare that PRLR blocking antibodies constitute a novel treatment option for women with endometriosis and different phase studies are underway trying to show their effects on humans.

Research Source: https://pubmed.ncbi.nlm.nih.gov/35084123/