The hypothalamic neuropeptide, corticotrophin-releasing hormone (CRH), which is also produced by human endometrium, has been shown to induce its decidualization in vitro. This process, induced mainly by progesterone, has characteristics of an aseptic inflammatory reaction, and is modulated by locally produced pro-inflammatory factors. In humans, prostaglandin E(2) (PGE(2)) enhances while interleukin (IL)-1 inhibits the decidualizing effect of progesterone. The aim of the present work was to test the hypothesis that CRH might affect the decidualization of human endometrium interacting with these factors. Therefore, we studied its effects on the production of pro-inflammatory interleukins IL-1, IL-6 and of PGE(2) from human endometrial stromal cells in primary culture. The results strongly suggest that CRH decidualizes stromal cells, as judged by the appearance of cytokeratins and the production of prolactin, two established markers of decidualization. In parallel to its effect on decidualization, CRH also decreased the production of PGE(2), while it increased the production of IL-1 and IL-6. Exposure of endometrial stromal cells to IL-6 also caused decidualization. The data presented here suggest that endometrial CRH regulates the production of local modulators of decidualization, i.e. PGE(2), IL-1 and IL-6. We postulate that, through the regulation of these factors, CRH acts as a local fine-tuner of decidualization initiated by progesterone.
Corticotropin-releasing hormone (CRH) is synthesized in most female reproductive tissues such as the ovaries and the uterus. In the non-pregnant uterus, it is mainly produced by epithelial cells of the endometrium. Recent in vitro experimental findings show that endometrial CRH is under the positive control of progesterone, participating in the decidualization process of endometrial stroma and the progression of blastocyst implantation. CRH is also produced in the thecal compartment of the human ovary, controlling ovarian steroid hormone biosynthesis. In the present study we compared the concentration of immunoreactive CRH (ir-CRH) in biopsies from proliferative and secretory human endometria, and from pre- and postmenopausal human ovaries. We found that the concentration of ir-CRH was significantly higher in the secretory (92 +/- 8 pg/mg protein; n = 10) than the proliferative (75 +/- 9 pg/mg protein; n = 12; p < 0.05) endometria. This observation supports the experimental in vitro findings associating endometrial CRH in intrauterine phenomena of the secretory phase of the menstrual cycle (decidualization and implantation). Additionally, we have shown that the concentration of ir-CRH was significantly higher in the premenopausal (125 +/- 12 pg/mg protein; n = 14) than the postmenopausal (100 +/- 12 pg/mg protein; n = 12; p < 0.05) ovaries, suggesting that ovarian CRH is related to normal ovarian function during the reproductive lifespan.
The aim of this study was to investigate the efficacy of recombinant human erythropoietin (rHuEPO) combined with parenteral iron, in the treatment of moderate and severe iron deficiency anemia during pregnancy. Twenty-six pregnant women, who had been ineffectively treated with iron supplementation alone for at least 8 weeks, were enrolled. They met the following criteria for inclusion in the study: hemoglobin (Hb) concentration <8.5 g/dl, evidence of iron deficiency anemia, and absence of other pregnancy complications, or severe systemic diseases. The treatment protocol comprised of a combination therapy with 150 IU/kg rHuEPO subcutaneously three times per week and 100 mg parenteral iron daily, for a total period of 4 weeks. Nineteen out of 26 women (73%) showed a quick response, with Hb reaching normal levels within the first 2 weeks of treatment. They displayed an average of 3.17 g/dl increase in Hb concentration during the total period of therapy, with 3.0 g/dl increase within the first 2 weeks. In 5 women (19.2%) there was no significant increase in Hb levels, while in 2 women (7.6%) a further decline in Hb concentration was observed, that necessitated a blood transfusion. In conclusion, rHuEPO combined with parenteral iron is an effective treatment for moderate and severe iron deficiency anemia during pregnancy, with minimal adverse or side effects. It may serve as an alternative to blood transfusion, or in cases of resistant anemia that are not effectively treated by iron supplementation alone. However, further studies are needed to investigate the poor response observed in about 25% of treated patients.
Corticotropin-releasing hormone (CRH) is synthesized in most female reproductive tissues such as the ovaries and the uterus. In the non-pregnant uterus, it is mainly produced by epithelial cells of the endometrium. Recent in vitro experimental findings show that endometrial CRH is under the positive control of progesterone, participating in the decidualization process of endometrial stroma and the progression of blastocyst implantation. CRH is also produced in the thecal compartment of the human ovary, controlling ovarian steroid hormone biosynthesis. In the present study we compared the concentration of immunoreactive CRH (ir-CRH) in biopsies from proliferative and secretory human endometria, and from pre- and postmenopausal human ovaries. We found that the concentration of ir-CRH was significantly higher in the secretory (92 +/- 8 pg/mg protein; n = 10) than the proliferative (75 +/- 9 pg/mg protein; n = 12; p < 0.05) endometria. This observation supports the experimental in vitro findings associating endometrial CRH in intrauterine phenomena of the secretory phase of the menstrual cycle (decidualization and implantation). Additionally, we have shown that the concentration of ir-CRH was significantly higher in the premenopausal (125 +/- 12 pg/mg protein; n = 14) than the postmenopausal (100 +/- 12 pg/mg protein; n = 12; p < 0.05) ovaries, suggesting that ovarian CRH is related to normal ovarian function during the reproductive lifespan.
In women with an adnexal mass, ascites and elevated Ca-125 levels, ovarian carcinoma must be ruled out. However, several other conditions, including genital tuberculosis, may present similarly. A 41-year-old woman with weight loss, ascites and elevated levels of Ca-125 was evaluated for ovarian cancer. Computerized tomography revealed an adnexal mass, ascites and lymphnodes on the peritoneal surface. Paracentesis of the ascitic fluid revealed a lymphocytic exudate but failed to show any malignant cells. At laparotomy, frozen sections of tissue biopsies were negative for malignancy; however, a total hysterectomy plus adnexectomy was performed. Postoperatively histologic examination revealed typical features of genital tuberculosis. Antituberculosis treatment was effectively given to the patient. Serum levels of Ca-125 were undetectable 12 weeks after treatment. In conclusion, genital tuberculosis can be misdiagnosed and confused with ovarian cancer. Intraperitoneal tuberculosis should be considered in the differential diagnosis in cases in which ovarian cancer is suspected, even when malignancy-associated risk factors are present.
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