Regulated expression of matrix metalloproteinases, inflammatory mediators, and endometrial matrix remodeling by 17beta-estradiol in the immature rat uterus

<p>Abstract</p> <p>Background</p> <p>Administration of a single physiological dose of 17beta-estradiol (E2:40 microg/kg) to the ovariectomized immature rat rapidly induces uterine growth and remodeling. The response is characterized by changes in endometrial stromal architecture during an inflammatory-like response that likely involves activated matrix-metalloproteinases (MMPs). While estrogen is known as an inducer of endometrial growth, its role in specific expression of MMP family members in vivo is poorly characterized. E2-induced changes in MMP-2, -3, -7, and -9 mRNA and protein expression were analyzed to survey regulation along an extended time course 0-72 hours post-treatment. Because E2 effects inflammatory-like changes that may alter MMP expression, we assessed changes in tissue levels of TNF-alpha and MCP-1, and we utilized dexamethasone (600 microg/kg) to better understand the role of inflammation on matrix remodeling.</p> <p>Methods</p> <p>Ovariectomized 21 day-old female Sprague-Dawley rats were administered E2 and uterine tissues were extracted and prepared for transmission electron microscopy (TEM), mRNA extraction and real-time RT-PCR, protein extraction and Western blot, or gelatin zymography. In inhibitor studies, pretreatment compounds were administered prior to E2 and tissues were harvested at 4 hours post-hormone challenge.</p> <p>Results</p> <p>Using a novel TEM method to quantitatively assess changes in stromal collagen density, we show that E2-induced matrix remodeling is rapid in onset (< 1 hour) and leads to a 70% reduction in collagen density by 4 hours. Matrix remodeling is MMP-dependent, as pretreatment with batimastat ablates the hormone effect. MMP-3, -7, and -9 and inflammatory markers (TNF-alpha and MCP-1) are transiently upregulated with peak expression at 4 hours post-E2 treatment. MMP-2 expression is increased by E2 but highest expression and activity occur later in the response (48 hours). Dexamethasone inhibits E2-modulated changes in collagen density and expression of MMPs although these effects are variable. Dexamethasone upregulates MMP-3 mRNA but not protein levels, inhibiting E2-induced upregulation of MMP-7, and -9, and MCP-1 mRNA and protein but not inhibiting the hormone-induced increase in TNF-alpha mRNA.</p> <p>Conclusion</p> <p>The data demonstrate that E2-regulated endometrial remodeling is rapid in onset (<1 hour) and peak expression of MMPs and inflammatory mediators correlates temporally with the period of lowest stromal collagen density during uterine tissue hypertrophy.</p

Premenstrual seizure increase influence of age, duration of disease, seizure frequency, previous complaint of perimenstrual accentuation, eeg and ct scan findings

We selected prospectively 80 mentally healthy women at menacme age, with chronic epilepsy and at least one seizure in the month preceding this study. They underwent four EEGs weekly. CT scan of the skull was done in 57 patients (71.25%). Seven patients were excluded because they had no seizures or menses. We registered 5630 seizures during 579 regular menstrual cycles over a 30 month period. RESULTS: - there was a higher incidence of seizures in the premenstrual period (p<0.001); - age did not influence the distribution of seizures during the menstrual cycle in the group studied; - patients with 11 or more years of disease showed more accentuation of premenstrual seizures than patients with 10 or less years of disease; - there was no relation between the patients frequency of seizures and the occurrence of premenstrual seizures; - the patients impression of the incidence of seizures not related to menstruation was not confirmed; - patients with abnormal skull CT scans had more accentuation of premenstrual seizures than patients with normal exams; - patients with abnormal EEGs had more premenstrual seizures than patients with normal exams. Our findings suggest that the female sexual hormones alter cerebral excitability when there is an underlying structural pathology shown by CT scan or an electrical cerebral dysfunction revealed by EEG