Leptin, its receptor and aromatase expression in deep infiltrating endometriosis

Abstract

BackgroundThe aim of this study was to evaluate the leptin levels in the serum and peritoneal fluid (PF) and the protein expression in three different peritoneal ectopic implants in patients who underwent surgery for deep infiltrating endometriosis.MethodsAll patients had been treated at the Department of Gynecology of the Pedro Ernesto University Hospital, Rio de Janeiro. The study group consisted of 15 patients who underwent surgery for adnexal masses and infertility, while the control group consisted of ten women who underwent surgery for tubal ligation. Peritoneal fluid and samples tissues were collected during surgery. Serum samples were obtained before anesthesia. In this study, the leptin levels in the serum and peritoneal fluid (PF) were evaluated by ELISA. The protein expression of leptin and its receptors (ObR) and aromatase enzyme were evaluated by Western blot analysis of the intestine, uterosacral ligament and vaginal septum in the ectopic implants. The t-test and one-way ANOVA with Holm-Sìdak post-test were used, and p < 0.05 was considered to be statistically significant.ResultsCompared to the controls, the serum leptin levels (control = 14.7 ng/mL ± 2.63, endometriosis = 19.2 ng/mL ± 1.84, p < 0.0001) were increased, while in PF, there was no difference (control = 6.68 ng/mL ± 0.43, endometriosis = 7.71 ng/mL ± 0.59, p = 0.18). Comparing women with and without ovarian implants, the leptin levels in both the serum and PF were significantly higher in women without ovarian implants (serum: with ovarian implant = 15.85 ± 1.99; without ovarian implant = 23.14 ± 2.60; ng/mL, p = 0.04; PF: with ovarian implant = 4.28 ± 1.30; without ovarian implant = 11.18 ± 2.98;ng/mL, p = 0.048). The leptin, ObR and aromatase protein expression levels were increased in lesions in the vaginal septum and were decreased in the intestine lesions.ConclusionThis study reports several interesting associations between the leptin levels in serum, peritoneal fluid, and tissue samples and the localization of the ectopic endometrium. Although this study does not provide a clear picture of the role of leptin in the development and progression of peritoneal implants, it contributed new data that might be useful to elucidating the enigma that is the role of leptin in endometriosis disease.

Higher fibrotic content of endometriotic lesions is associated with diminished prostaglandin E2 signaling

“… 63 When a sizeable portion of tissue samples came from DE lesions, the evidence for aromatase positivity could easily evaporate. 64 , 65 , 66 , 67 This is because as lesions become more fibrotic and thus more rigid, the PGE 2 signaling would be attenuated, effectively cutting off this putative induction pathway.…”

The Formidable yet Unresolved Interplay between Endometriosis and Obesity

“…In a case-control study of 44 women with endometriosis and 42 healthy controls, Choi et al showed that leptin had an expression rate of 100% in ovarian endometrioma tissue specimens versus 59.5% in normal endometrium ( p < 0.001), independent of BMI or stage of disease [ 61 ]. Furthermore, Gonçalves et al found that leptin concentration in peritoneal fluid did not differ between patients and control ( p 0.18), and there was only borderline difference between those with ovarian implants and without them ( p 0.048) [ 57 ]. On the contrary, serum leptin levels were significantly higher both in patients versus controls ( p < 0.0001) and in those without ovarian implants versus those with implants ( p 0.04).…”

“…e action of leptin is roughly opposite to that of ghrelin, but its exact role depends on the energy state of the body: in steady body weight, it reflects the content of body fat; in cases of weight excess, its increased concentrations reduce appetite through central nervous signaling, whereas in conditions of food restriction, its levels decline in order to meet increased energy demands [44]. Apart from its metabolic properties, leptin is also known as a proinflammatory and angiogenetic mediator [55][56][57]. Increased levels of leptin have been identified in serum and peritoneal fluid specimens from women with endometriosis for more than two decades [55,58].…”

Endometriosis: where are we and where are we going?

“…Aromatase protein level is increased in vaginal septum lesions and decreased in intestinal lesions in women with endometriosis (Goncalves et al 2015). Ovarian endometriomas express higher levels of aromatase and peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PPARGC1A) than associated ectopic lesions and eutopic endometrium (Suganuma et al 2014).…”