Penetration of pesticides in the human reproductive system. Presentation of case reports.
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Abortion, Induced↗
Biomedical subjects
A Makrigiannakis
Publications and source records attributed to A Makrigiannakis.
Corticotropin releasing hormone (CRH) in normal and pregnant uterus: physiological implications.
Corticotropin-releasing hormone, is a hypothalamic neuropeptide, responsible not only for the endocrine but also the autonomic, immunological and behavioural responses of mammalian organisms to stress. CRH is also expressed in female reproductive tissues, such as placenta and uterus. Multiple sites within the pregnant uterine cavity express the CRH gene, including the trophoblasts, fetal membranes (chorion, amnion) and decidua. The trophoblastic syncytium appears to be the major source of placental CRH. It is postulated that placental CRH influences the HPA axis of either mother or fetus and participates at the initiation of labour. Recent findings show that human and rat uterus express the CRH gene. Epithelial cells of both species are the main source of endometrial CRH, while stroma does not seem to express it, unless it differentiates to decidua. Estrogens and glucocorticoids inhibit and prostaglandin E2 stimulates the promoter of human CRH gene in transfected human endometrial cells, suggesting that endometrial CRH gene expression is under the control of these agents. Moreover, in rats, endometrial CRH expression is significantly higher at the implantation sites, compared to that at the inter-implantation uterine regions. Given the proinflammatory/vasoregulatory properties of CRH, we hypothesize that endometrial CRH may participate in the regulation of intrauterine phenomena, such as blastocyst implantation, endometrial vascularization and myometrial contractility.
Animals↗
Regulation of the promoter of the human corticotropin-releasing hormone gene in transfected human endometrial cells.
Corticotropin-releasing hormone (CRH) is expressed in several peripheral tissues, including normal epithelial cells of the human and rodent uterus. However, the biological role of endometrial CRH is known in neither species. As a first step to clarify this role, we studied the regulation of CRH promoter in endometrial cells. We performed homologous transfection experiments in Ishikawa cells, a human endometrial cell line, using a 0.9-kb fragment of the 5'-flanking region of the human CRH gene coupled to luciferase. Transfected cells were exposed for 18 h to 8-bromo cyclic adenosine monophosphate, forskolin, epidermal growth factor, steroids (estradiol, progesterone, and the synthetic glucocorticoid dexamethasone and their antagonists), and prostaglandin E2; then the activity of the luciferase reporter was determined in the cell lysates. We found that the activity of the 5'-flanking region of the CRH gene was stimulated by cyclic adenosine monophosphate and epidermal growth factor and inhibited in a receptor-mediated, dose-dependent fashion by estradiol and dexamethasone. The antiglucocorticoid RU 486 acted as a glucocorticoid agonist, suppressing the CRH gene activation, while progesterone was devoid of any activity. Prostaglandin E2 stimulated the CRH activation, and the prostanoid inhibitor indomethacin suppressed it, most probably by inhibiting endogenous prostaglandins. These findings suggest that endometrial CRH gene expression may be under the negative control of estrogens and glucocorticoids and under the positive control of prostaglandin E2.
Adenocarcinoma↗
Teratoma of the placenta. A case report.
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Adult↗
Corticotropin-releasing hormone (CRH) is expressed at the implantation sites of early pregnant rat uterus.
We have shown previously that the epithelial cells of human endometrium produce CRH. The biological role of endometrial CRH is not yet known. Among other things, CRH appears to be involved in the inflammatory process, acting as an autocrine/paracrine proinflammatory regulator. Since the reaction of endometrium to the invading blastocyst has characteristics of an aseptic inflammatory reaction, we have hypothesized that endometrial CRH may participate in the inflammatory phenomena taking place at the implantation site of blastocyst. In the present study we demonstrate a higher content of immunoreactive (IR)-CRH and CRH mRNA in the implantation sites of early pregnant rat uterus compared to the inter-implantation regions. Specifically we have found that: a) rat uterus contained a 1.3 kb CRH transcript, similar or identical in size to that present in human placenta, b) the size of the IR-CRH present in uterine extracts was similar to authentic hypothalamic CRH, c) Northern blot analysis showed that the content of CRH mRNA in uterus at the implantation sites was 3.5 fold higher compared to that in the inter-implantation regions and finally, d) immunohistochemical localization of IR-CRH in early pregnant rat uterus revealed positive staining of the luminal epithelial cells in both implantation and inter-implantation uterine regions, while decidualized stromal cells were positive only at the implantation sites. Our data suggest that endometrial CRH may play a role in the implantation of blastocyst.
Animals↗
The corticotropin-releasing hormone (CRH) in normal and tumoral epithelial cells of human endometrium.
CRH is produced by several intrauterine sites, including placenta and desidua, during pregnancy. However, no data are available regarding the presence of CRH in the nonpregnant uterus. We now report that CRH is produced in the epithelial cells of normally cycling human uterus and in an endometrial epithelial cell-derived tumor. Specifically, we have found that: 1) Northern blot hybridization analysis of normal glandular endometrium as well as of Ishikawa human endometrial adenocarcinoma cells showed the presence of the CRH messenger RNA; the size of the transcript seemed to be identical to that present in human placenta and rat hypothalamus; 2) immunoreactive CRH (ir-CRH) was detectable in normal dispersed glandular endometrial cells as well as in the Ishikawa adenocarcinoma cells; 3) gel filtration chromatography of normal glandular endometrial and Ishikawa cell extracts and their culture media showed that most ir-CRH present had the mol wt of the authentic CRH peptide; in addition, a larger form of ir-CRH was also present in both normal and tumoral endometrial epithelial cell extracts; the latter most probably correspondents to CRH precursor molecules; and 4) immunofluorescence staining of CRH in normal glandular endometrial and Ishikawa cells revealed a cytoplasm rich in granules positive for ir-CRH. Our findings suggest that CRH may play an important role in the physiological events taking place within the uterine cavity, since CRH seems to be present in nonpregnant as well as pregnant uteri. Since CRH is expressed in normal endometrial epithelial cells and in an epithelial tumoral cell line, we propose the use of the Ishikawa cell line as a convenient model for the in vitro study of endometrial CRH.
Adenocarcinoma↗
Interaction between steroid hormones and endometrial opioids.
The opioids beta-endorphin and the dynorphins belong to two separate families of endogenous opioid peptides (EOP). They are produced not only in the central nervous system but also in nonneural tissues where, as it appears, they act locally via paracrine mechanisms. These opioids have been shown to be produced at multiple sites along the mammalian reproductive tract including the intrauterine cavity. The aim of the present work was to find out if the well differentiated human endometrial cell line of Ishikawa, which has been shown to be a good in vitro model for the study of the effects of steroid hormones on human epithelial endometrium, expresses these two EOP. Northern blot hybridization of RNA from these cells showed the presence of a 1.2-kb POMC and a 2.4-kb PDYN transcript. Radioimmunoassay and gel filtration chromatography characterization of the immunoreactive (IR) opioid peptides present in the culture media showed the presence of IR-beta-endorphin and IR-dynorphins. The apparent molecular weight of IR-beta-endorphin was that of authentic beta-endorphin while the bulk of the IR-dynorphin had an apparent molecular weight of 8 kd. The secretion of both opioids could be increased by KCl-induced depolarization. Estrogen and glucocorticoids decreased, in a dose- and time-dependent manner, the secretion of beta-endorphin from the Ishikawa cells while progesterone and dihydrotestosterone did not have a statistically significant effect. The antiprogestin-antiglucocorticoid RU486 acted as an agonist, i.e., it diminished beta-endorphin secretion possibly via glucocorticoid receptors. On the other hand, the secretion of dynorphins was not affected by any of the steroids tested while LHRH, the inducer of gonadotropins and anterior pituitary dynorphins secretion, provoked a time- and dose-dependent increase of their secretion without affecting that of beta-endorphin. These data suggest that the regulation of endometrial opioids production is type-specific. Thus, it is possible that each type of endometrial opioid participates in different local homeostatic loops and exerts distinct paracrine effects.
Adenocarcinoma↗
[Pneumoperitoneum without perforation].
Usually, pneumoperitoneum is due to perforation of a hollow abdominal organ. In the absence of peritoneal symptoms, pneumoperitoneum may be due to other causes. Two patients with pneumoperitoneum without perforation were treated in our department. A 41-year-old female patient was admitted to our hospital with abdominal pain for 12 hours, without vomiting. On abdominal examination fullness of the liver was absent, the abdomen was not distended and there were no signs of peritoneal irritation. The roentgenogram showed free air under the diaphragm. Laparotomy was performed because of the abdominal complaints. No perforation could be found. A 70-year-old female patient was admitted to the hospital because of mild abdominal pain. For a week she had a severe attack of coughing due to bronchitis. Big capacity of air had been blown in the stomach without abnormalities in the roentgenologic examination. The treatment was conservative. Both patients left the hospital in good health. More knowledge of the less frequent causes of pneumoperitoneun without perforation can possibly contribute to to refraining from exploratory laparotomy in these cases.
Adult↗
PC12 rat pheochromocytoma cells synthesize dynorphin. Its secretion is modulated by nicotine and nerve growth factor.
The PC12 is a cloned rat pheochromocytoma cell line that retains a number of chromaffin cell characteristics, such as the presence of nicotinic cholinergic receptors, the synthesis and secretion of catecholamines, and the expression of a number of neuropeptide genes. The PC12 cell line is a useful model for the study of neuronal development, since PC12 cells can be induced to differentiate toward sympathetic neurons after exposure to nerve growth factor (NGF). PC12 cells can also be induced to differentiate toward the opposite direction, i.e. toward mature chromaffin cells. Morphological and biochemical changes mark the differentiation of PC12 cells toward either direction. Among the substances proposed as biochemical markers of PC12 cell differentiation toward chromaffin cells is the endogenous opioid precursor proenkephalin and its posttranslational peptide products. Indeed, the proenkephalin gene is expressed in both adrenal chromaffin and PC12 cells. The secretion of enkephalins from PC12 cells increases by several-fold after differentiation toward chromaffin cells. On the other hand, prodynorphin (another endogenous opioid precursor) is not present in normal adrenal chromaffin cells, but it is synthesized by human pheochromocytomas. It, thus, appears that dedifferentiation of chromaffin cells induces expression of the prodynorphin gene. Consequently, the aim of this study was to determine whether the rat pheochromocytoma-derived PC12 cell line expresses the prodynorphin gene, if it secretes dynorphins, and if the NGF-induced differentiation of PC12 cells toward sympathetic neurons affects the secretion of the latter. We found the following. 1) PC12 cells synthesize prodynorphin and secrete its peptide products. 2) The size of the prodynorphin transcript and the mol wt of its dominant form of dynorphin appear to be similar or identical to those of prodynorphin in rat anterior pituitary. 3) PC12 dynorphin secretion is increased, in a dose-dependent manner, after nicotinic cholinergic stimulation, an effect blocked by the specific nicotine antagonist hexamethonium. Thus, it appears that after cholinergic stimulation, PC12 dynorphin is cosecreted with catecholamines, a phenomenon described for a number of neuropeptides, including the proenkephalin-derived opioids. 4) The NGF-mediated differentiation of PC12 cells into sympathetic neurons exerted a stimulatory effect on basal, nicotine-induced, and depolarization-dependent dynorphin secretion. However, NGF did not shift the nicotine dose-response curve of dynorphin secretion. In conclusion, it appears that while changes in the secretion of proenkephalin-derived peptides may serve as a marker of PC12 cell differentiation toward chromaffin cells, an increase in the secretion of prodynorphin-derived peptides may represent a marker of NGF-induced differentiation of PC12 cells toward sympathetic neurons.
Animals↗
Steroid hormones regulate the release of immunoreactive beta-endorphin from the Ishikawa human endometrial cell line.
Immunoreactive beta-endorphin (IR-beta END) is present in human endometrium. Several indirect lines of evidence suggest that endometrial beta END is under steroid hormone control, i.e. IR-beta END is detectable in the secretory, but not the proliferative, endometrium, and progesterone administration increases the concentration of IR-beta END in uterine secretions of ovariectomized gilts. To study the effect of steroid hormones on endometrial beta END, we first questioned whether Ishikawa human endometrial adenocarcinoma cells (which respond to steroid hormones) express the proopiomelanocortin (POMC) gene. Indeed, on Northern blot analysis, a RNA similar or identical in size to pituitary POMC mRNA was present in Ishikawa cell RNA extracts. IR-beta END was also present in Ishikawa cell extracts and culture medium, which coeluted with synthetic human beta END in a Sephadex G-50 column. Ishikawa cells released most of their IR-beta END into the culture medium. Estradiol decreased the release of IR-beta END from Ishikawa cells, an effect that was dependent upon dose and time. The maximal effect was observed after a 4-day exposure to 10 nM estradiol (44 +/- 6% of the control value; n = 6; P less than 0.001). This effect was almost completely counteracted by a 100-fold excess of the antiestrogen 4-hydroxytamoxifen. Progesterone and dihydrotestosterone did not have a statistically significant effect on IR-beta END release. Dexamethasone had effects similar to those of estradiol, i.e. decreased the release of IR-beta END in a time- and dose-dependent manner. The maximal effect was detected after a 4-day exposure to 10 nM dexamethasone (53 +/- 6% of the control value; n = 6; P less than 0.001). Interestingly, the antiprogestin-antiglucocorticoid RU486 exhibited agonistic properties, i.e. diminished the release of IR-beta END in a time- and dose-dependent fashion, possibly via the glucocorticoid receptor. Its maximal effect was reached after a 4-day exposure to 10 nM RU486 (55 +/- 6% of the control value; n = 6; P less than 0.001). In conclusion, our data demonstrate that the release of IR-beta END from Ishikawa cells in culture is inhibited by estradiol and dexamethasone, suggesting that endometrial beta END is under estrogen and glucocorticoid regulation, as is the case with hypothalamic and pituitary POMC-derived peptides. This is the first time that the in vitro release of a peripheral-extracranial POMC-derived peptide has been found to be under the direct control of estrogens and glucocorticoids.
Dexamethasone↗
Use of CA-125 in the diagnosis and management of endometriosis: influence of treatment with danazol.
OBJECTIVE: To compare CA-125 levels in endometriotic women with normal controls. PATIENTS AND METHODS: The level of the oncofetal antigen CA-125 was measured in serum samples taken from 40 women, aged 21 to 33 years. Blood samples for CA-125 from 15 endometriotic women were measured before treatment, during the last 15 days of a 6-month administration of Danazol, and 3 months after treatment, and were compared to findings in 15 women without endometriosis (from whom blood samples were taken only once). RESULTS: The CA-125 levels were significantly higher in patients with endometriosis before treatment as compared with the controls (P < .01). The administration of Danazol significantly reduced the levels of CA-125 (P < .01), and 3 months after treatment the levels of CA-125 remained significantly lower (P < .05) as compared to the respective pretreatment values. CONCLUSION: The results support the view that the determination of CA-125 levels may assist in (a) evaluating women with endometriosis and (b) treatment with Danazol.
Adult↗
Cigarette smoking and vaginal atrophy in postmenopausal women.
The atrophy of the vaginal epithelium was studied clinically and cytologically on vaginal smears of 1638 healthy postmenopausal female non smokers and 531 healthy postmenopausal smokers (over 30 years), with a mean age of 58 years. A very strong statistically significant difference (p < 0.0001) in the atrophical vaginal changes between smokers and nonsmokers to the disadvantage of the smokers. Also a very statistically significant association (p < 0.0001) was observed between the cytological expression of the vaginal atrophy and duration at menopause of the non-smokers but no association in the cases of the smokers. Another important result of this study was that the smokers women had an early menopause (p < 0.0001), on average by 2 years sooner (mean age 48.5 years) than non-smokers (mean age 50.5 years). These results suggest that cigarette smoking has an effect on the vaginal squamous epithelium, increasing the atrophical changes and causing early menopause by mechanisms, some of which remain unclear.
Age of Onset↗