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Dopamine and Tumorigenesis in Reproductive Tissues
Published in Nira Ben-Jonathan, Dopamine, 2020
A recent study examined the effects of thioridazine, alone or in combination with medroxy-progesterone acetate (MPA), on endometrial cancer [83]. The combined treatment increased apoptosis in two endometrial cancer cell lines, ISK and KLE. Expression of both progesterone receptor B (PRB) and D2R increased, while that of EGFR and p-AKT decreased. These data suggested that thioridazine plus MPA suppress tumor growth by inhibiting the PI3K/AKT signal transduction pathway, which is mediated by PRB, D2R and EGFR. A functional association between DA and NO was seen in endometrial glandular epithelial cells isolated from human endometrial specimens [84]. DA caused a dose-dependent transient surge of NO, whereas estrogen, progesterone, or relaxin did not. Cells treated with relaxin or with DA for 4 days enhanced the DA-induced NO release four- to six-fold. It remains to be determined whether DA-induced NO release activates the cGMP/PKG apoptotic pathway also in endometrial cancer cells.
Recurrence of endometriosis
Published in Seema Chopra, Endometriosis, 2020
Endometriosis is a major contributor to disability and compromised quality of life of women. Early diagnosis is the need of the hour that requires a specific and sensitive biomarker for diagnosing endometriosis nonsurgically, thereby preventing late sequelae of endometriosis. The gold standard for diagnosis of endometriosis is visualization of lesions directly on laparoscopy or laparotomy and confirmation by histopathology, but it is associated with various side effects of surgery such as infection, bleeding, or injury to adjacent organs. Noninvasive tests are required for the diagnosis of endometriosis in patients with pelvic pain with normal ultrasound reports to detect endometriosis at an early stage. Increased progesterone receptor isoform B (PRB) and decreased nuclear factor kappa B immunoreactivity are found in the recurrent group. Further studies are needed to determine immunoreactivity with a larger number of kappa B and PRB as biomarkers for recurrent endometriosis [11].
Preterm labour
Published in Louise C Kenny, Jenny E Myers, Obstetrics, 2017
Progesterone is considered to play a major role in the maintenance of pregnancy. In most pregnant mammals, the onset of parturition is associated with a decrease in circulating progesterone through a variety of mechanisms including corpus luteum lysis in rodents and a reduction in placental progesterone synthesis in the sheep. However, in humans the levels of circulating progesterone remain elevated throughout pregnancy, but the administration of the progesterone receptor antagonist RU486 can induce labour. This suggests that although progesterone is involved in pregnancy maintenance, the onset of human labour either involves a functional withdrawal of progesterone action or occurs independent of any loss in progesterone activity. Current theories favour the former, invoking a change in progesterone receptor (PR) isoform expression, an increase in the antagonist PRA isoform and decline in the agonist PRB isoform, or a repression in PRB activity through activation of the inflammatory transcription factor nuclear factor kappa B (NFκB).
Uterine sparing management in patients with endometrial cancer: a narrative literature review
Published in Journal of Obstetrics and Gynaecology, 2022
Maria Zisi, Dimitrios Zygouris, Orestis Tsonis, Sofia Papadimitriou, Mastorakos George, Sophia Kalantaridou, Minas Paschopoulos
Recently have been studied several markers for predictions of the response of AEH and EC to conservative treatment and if they are available they should be taken into consideration in order to tailor management. A systematic review by Travaglino et al. showed that progesterone receptor and oestrogen receptor isoforms in the pre-treatment phase and nuclear factor erythroid 2‐related factor 2 (Nrf2), survivin, Bcell lymphoma 2 (Bcl2) and antigen Ki67 (Ki67) on follow up are the most useful markers of response to conservative treatment (Travaglino et al. 2019). More specific, decreased stromal expression of the isoform B of progesterone receptor (PRB) is highly indicative of both no response and recurrence of AEH and EEC that are conservatively treated (Raffone et al. 2021c). Furthermore the systematic review by Raffone et al. showed that oestrogen or progesterone receptor expression predicts the response to LNG-IUS but not to oral progestins in cases of uterine sparing treatment (Raffone et al. 2019b). Although deficient mismatch repair immunohistochemical expression does not imply resistance of AEH/EEC to conservative treatment it appears as a highly specific predictor of recurrence of AEH/EEC after initial regression (Raffone et al. 2021a).
Progesterone and human cognition
Published in Climacteric, 2018
Progesterone has multiple signaling pathways. It exerts its physiological effects primarily by binding to intranuclear progesterone receptors. The two main receptor isoforms, progesterone receptor-A and progesterone receptor-B, are found throughout the brain, and the expression and regulation differs for these two receptors1. There is also a third isoform, and progesterone binds to several membrane receptors and has other mechanisms of action. Progesterone is antagonistic to some effects of estradiol in the brain, but the relation is complex and their actions are at times synergistic2,3. Both play key roles in synaptic plasticity and neuroprotection2. Neuroprotective effects of progesterone have been demonstrated in animal models of traumatic brain injury, spinal cord injury, stroke, and neurodegeneration. However, results of human trials of progesterone for neuroprotection after traumatic brain injury are disappointing4,5. There is convincing evidence, at least in rodents, that progesterone enhances object memory and affects other cognitive abilities6. In cycling cynomolgus monkeys, however, the concentration of serum progesterone was associated with poorer performance on a discrimination task and was unrelated to other cognitive performance measures7.
Low-dose aspirin can downregulate progesterone resistance and increase the expression of LIF in endometriosis during the implantation window
Published in Gynecological Endocrinology, 2021
Lihui Wang, Jing Zhang, Hui Zhang, Rui Li, Chunyan Li, Xingbo Zhao, Mingjiang Li
Progesterone is involved in the regulation of the endometrial cycle by binding to its receptor. Progesterone receptor (PR) includes two isoforms with different functions, named PRA and PRB. Null-mutation of both PR isoforms caused infertility of mice [1]. Some studies report that progesterone resistance leads to less reception for embryo implantation. The possible mechanisms included aberrant cell signaling pathways and reduced expression of key homeostatic proteins in endometriosis [1,11].