The effects of prolactin receptor blockade in a murine endometriosis interna model.

Endometriosis in an estrogen-dependent disease that is characterized by the presence of endometrial tissue outside the uterine cavity leading to pain and infertility in many affected women. Highly efficient treatment options which create a hypo-estrogenic environment can cause side effects such as hot flushes and bone mass loss that are not favorable for premenopausal women. Previous work has demonstrated that increased local or systemic prolactin seems to be involved in the pathogenesis of endometriosis. Here we examined two prolactin receptor (PRLR) blocking antibodies in a murine endometriosis interna model which relies on the induction of systemic hyperprolactinemia in female SHN mice. The severity of the disease is determined by the degree of endometrial invasion into the myometrium. In this model, endometriosis was inhibited by clinical gold standards such as progestins and anti-estrogenic approaches. PRLR blockade completely inhibited endometriosis in this mouse model to the same extent as the anti-estrogen faslodex or the GnRH antagonist cetrorelix. In contrast to cetrorelix and faslodex, the PRLR antibodies did not decrease relative uterine weights and were thus devoid of anti-estrogenic effects. We therefore hypothesize that PRLR antibodies may present a novel and highly efficient treatment option for endometriosis with a good safety and tolerability profile. Clinical studies are on the way to test this hypothesis.

Combined effect of fulvestrant and low dose BPA: comparative implications on EMT, apoptosis, and TGF-ß1 signaling in HepG2 cells.

Bisphenol A (BPA) is an endocrine-disrupting chemical utilized in the manufacture of food packaging, dental materials, medical devices, children's toys, and baby products. Numerous studies have indicated the role of BPA in the etiology of many diseases such as diabetes, cardiovascular diseases, obesity, cancer, and chemotherapeutic resistance. However, the effects of BPA- chemotherapeutic combination remain to be investigated in different cell lines. Here, we demonstrate that low dose BPA and fulvestrant (estrogen receptor antagonist) combination synergistically decrease proliferation, promote cell migration and mesenchymal transition, switching from E-cadherin to N-cadherin expression Hepg2 cells. Moreover, we determined that low dose BPA may evoke susceptibility to apoptosis in HepG2 cells. The mechanism underlying these effects has been identified as increased TGF-ß1 signaling. Our results provide an experimental basis for evaluating the potential health risks of low-dose BPA for fulvestrant therapy in hepatocytes.