Epilepsy in women. Oestrogen and progesterone plasma levels

Summary Comparison is made between numbers of fits and estrogen, progesterone plasma values during the menstrual cycle of women with epilepsy. All six cycles in women with ovulation had a significant positive correlation between estrogen/progesterone ratio and scores of fits. Three periods without ovulation all showed a significant correlation to estrogen variations.Acknowledgments. This work was supported by Gunvor och Josef Anérs stiftelse, Med. fac. University of Umeå, The Swedish Medical Research Council (Proj. No. 2148) and Karl Oskar Hansson's fund.     

循环雌二醇及代谢物与绝经后乳腺癌的相关性

目的探讨循环雌二醇（E2）、4-羟雌二醇（4-OHE2）、2-甲氧雌二醇（2-MOE2）水平及4-羟雌二醇：2-甲氧雌二醇（4-OHE2：2-MOE2）比值与绝经后乳腺癌危险性的相关性。方法采用ELISA法检测绝经后34例乳腺癌、40例乳腺良性（乳腺纤维腺瘤与乳腺囊性增生病）疾病患者和20例正常对照循环雌二醇、4-羟雌二醇、2-甲氧雌二醇水平并计算4-羟雌二醇：2-甲氧雌二醇比值。结果乳腺癌组及乳腺良性疾病组循环2-甲氧雌二醇水平差异无统计学意义（P〉0．05）,但均较正常对照组低（P〈0．05）;乳腺癌组及乳腺良性疾病组4-羟雌二醇：2、甲氧雌二醇比值差异无统计学意义（P〉0．05）,但均较正常对照组升高（P〈0．05）。乳腺癌Ⅰ期～Ⅲ期各期循环雌二醇、4．羟雌二醇、2-甲氧雌二醇、4-羟雌二醇：2-甲氧雌二醇比值差异无统计学意义（P〉0．05）。4-羟雌二醇、2．甲氧雌二醇、4．羟雌二醇：2-甲氧雌二醇比值在乳腺癌ER（-）组与ER（＋）组间差异无统计学意义（P〉005）,但ER（＋）组雌二醇水平较ER（-）组明显升高（P〈0．05）。结论2．甲氧雌二醇与绝经后乳腺疾病负相关;4-羟雌二醇：2-甲氧雌二醇比值可能预示绝经后乳腺疾病危险。     

Effect of sex hormones on uric acid metabolism in rats.

The effects of sex hormones on purine metabolism were investigated in rats. No influence on purine synthesis was shown by the injection of estrogen and androgen. The plasma urate levels were significantly lowered from 2.43 +/- 1.04 mg/100 ml to 1.53 +/- 0.57 mg/100 ml by the injection of progesterone. Urinary excretion of uric acid plus allantoin was slightly reduced. These results suggested that progesterone may influence age and sex differences in human plasma urate levels.     

Effect of progesterone on the in vivo binding of estrogens by uterine cells.

Progesterone selectively inhibits estradiol uptake by the nuclei of the luminal epithelial cells but not by other uterine cells. This inhibition in estrogen binding parallels the inhibition by progesterone of some estrogenic responses in the luminal epithelial cells only.     

Changes in olfactory perception during the menstrual cycle

The aim of the study was to find correlations between changes in olfactory sensitivity and the menstrual cycle. 14 young, healthy volunteers participated in the experiments. Subjects menstruated regularly and did not use oral contraceptives. Three odorants were investigated: phenylethyl alcohol, androstenone, and nicotine. Dilution series of the odorants were prepared, and presented to the subjects in order to determine the detection thresholds (triple forced choice). Additionally, the subjects' hedonic estimates of the odorants were measured, and mood states as well as hormonal levels of LH and estrogen were determined. Before the actual experiments started, subjects participated in three training sessions. One experiment was subdivided into 5 phases (two pre- and two postovulatory phases; one ovulatory phase). Only with regard to androstenone did trend analyses reveal a significant quadratic relationship between hedonic estimates and phases of the menstrual cycle, peaking at ovulation. Olfactory sensitivity was not significantly influenced by the menstrual cycle.     

Changes in olfactory perception during the menstrual cycle

Summary The aim of the study was to find correlations between changes in olfactory sensitivity and the menstrual cycle. 14 young, healthy volunteers participated in the experiments. Subjects menstruated regularly and did not use oral contraceptives. Three odorants were investigated: phenylethyl alcohol, androstenone, and nicotine. Dilution series of the odorants were prepared, and presented to the subjects in order to determine the detection thresholds (triple forced choice). Additionally, the subjects' hedonic estimates of the odorants were measured, and mood states as well as hormonal levels of LH and estrogen were determined. Before the actual experiments started, subjects participated in three training sessions.One experiment was subdivided into 5 phases (two pre- and two postovulatory phases; one ovulatory phase). Only with regard to androstenone did trend analyses reveal a significant quadratic relationship between hedonic estimates and phases of the menstrual cycle, peaking at ovulation. Olfactory sensitivity was not significantly influenced by the menstrual cycle.     

Secificity of mouse endocervical cell response progesterone: presence of receptors]

The mouse cervical cell response to progesterone, corticosterone, and androgens was studied in vitro and comparatively by grafts on males. Contrary to the exocervical cells which responded more or less to the three steroid hormones, the endocervical cells responded exclusively to progesterone even in an estrogen free system. This result suggests the existence in the mouse endocervical cells of specific receptors to progesterone and indicates that the squamons cells of the uterine cervix have a different response to steroid hormones depending on where these cells are located.     

Immunohistochemical evidence that tumors elicit the synthesis of estrogen receptors in the submandibular gland of female rats

We have demonstrated the presence of estrogen receptor mRNA and the mature protein in the cytoplasm and nucleus, respectively, of a 9,10-dimethyl-1,2-benzathracene-induced submandibular gland tumor in female rats. We have previously shown that progesterone receptors are also present in human salivary gland tumors. These results suggest that endocrine therapy may be effective in treatment of submandibular gland tumors.     

Luteolytic action of LHRH in women]

Several subcutaneous administrations of 250 microgram of LHRH (4 or 5 adminstrations at 4-hourly intervals per day) between the 2nd and 7th day post-ovulation in 4 normal women led to early luteolysis as demonstrated by a fall in serum progesterone concentration and early onset (2 to 3 days earlier) of menstruation.     

Dexamethasone suppression of ovulation in PMS-treated immature rats.

A single injection of 2.0 mg/kg dexamethasone (DXM) administered at 51 h after pregnant mare serum gonadatropin (PMS) treatment inhibited both ovulation and luteinization. S.c. injection of human chorionic gonadotropin (HGG) caused ovulation and luteinization in DXM-PMS-treated rats, whereas treatment with ACTH failed to overcome the DXM inhibitory effect. These findings are interpreted to indicate that DXM inhibits ovulation through a mechanism which might involve the central nervous system.     

COX-2与CYPlBl在人乳腺癌中的表达及意义

目的探讨人乳腺癌组织中COX-2和CYPlBl的表达规律及与临床病理特征的关系,对认识其在乳腺癌发生发展中的作用奠定初步病理学基础。方法应用免疫组织化学方法检测42例乳腺癌组织中COX-2和CYPlBl的表达情况,结合临床病理指标进行研究分析。结果在乳腺癌中COX-2和CYPIBl表达阳性率分别为78．6％和73．8％。COX-2的阳性表达与乳腺癌淋巴结转移、组织学分级显著相关（P〈0．05）;CYPlBI的阳性表达与组织学分级、ER表达显著相关（P〈0．05）。乳腺癌COX-2与CYPlBI表达呈正相关（r=0．481,P〈0．01）。结论人乳腺癌组织存在COX-2与CYPlBl的共同阳性表达,COX-2可能促进CYPlBl表达,共同作用参与乳腺癌的发生发展。     

Telomeres and meiosis in health and disease

Meiotic dysfunction increasingly afflicts women as they age, resulting in infertility, miscarriage and handicapped offspring. How aging disrupts meiotic function in women remains unclear, but as women increasingly delay childbearing, this issue becomes urgent. Telomeres, which mediate aging in mitotic cells, may also mediate aging during meiosis. Telomeres shorten during DNA replication. In mammals, oocytes remain quiescent, but their precursors replicated during fetal oogenesis. Moreover, eggs ovulated from older women entered meiosis later during fetal oogenesis than eggs ovulated when younger, and therefore underwent more replications. Telomeres also shorten from reactive oxygen, which triggers a DNA repair response, so the prolonged interval between fetal oogenesis and ovulation in some women would further shorten telomeres. Mice normally do not exhibit age-related meiotic dysfunction (interestingly, their telomeres are manyfold longer than telomeres in women), but genetic or pharmacologic shortening of mouse telomeres recapitulates the reproductive aging phenotype of women. This has led to a telomere theory of age-related meiotic dysfunction in women, and underlined the importance to human health of a mechanistic understanding of telomeres and meiosis.     

The involvement of serotonin in induced ovulation in the immature rat.

In pregnant mare's serum gonadotropin (PMS) treated immature rats the cortex, cerebellum, caudate nucleus and hypothalamus were isolated and analyzed for their serotonin (5-HT) content at 6-h intervals for 72 h. Results showed a general trend of significant variation occurring in days 1 and 3 after PMS injection with no major variations observed on the second day. The results obtained suggest a possible involvement of 5-HT in the control of ovulation.     

Effect of Progesterone on the in vivo binding of estrogens by uterine cells

Summary Progesterone selectively inhibits estradiol upltake by the nuclei of the luminal epithelial cells but not by other uterine cells. This inhibition in estrogen binding parallels the inhibition by progesterone of some estrogenic responses in the luminal epithelial cells only.Acknowledgments. This work was supported by Grant No. 2015 From the Oficina Técnica de Desarrollo Cientifico y Creación Artística of the University of Chile.     

Plasma estrogens in Pleurodeles waltlii. Comparison between diploid and triploid females]

Estrogens have been examined in the plasma of diploid and triploid newts Pleurodeles waltlii. Estradiol-17 beta (E2) and estrone (E1) were determined by radioimmunoassay, before and after enzymatic hydrolysis of the conjugates. Total (t) and unconjugated (u) E2 levels were positively correlated (E2u = 0.478 35 E2t + 0.579 98; r = 0.883), but no correlation was detected between E1 levels. No statistical difference was found for the estrogen levels between the different experimental lots of diploid newts (E2t = 7.5 +/- 0.37 ng/ml, E2u = 4.3 +/- 0.20 ng/ml, E1t = 2.19 +/- 0.08 ng/ml, E1t = 0.41 +/- 0.02 ng/ml) but every estrogen level was lower in the triploid group (E2t = 1.8 +/- 0.60, E2u = 1.0 +/- 0.18, E1t = 1.4 +/- 0.13, E1u = 0.3 +/- 0.04 ng/ml). This difference is discussed in relation to lower fertility of the triploid females.     

Synthesis of ovulation-inhibiting compounds; structure-activity relationship.

We describe the synthesis of some new derivatives of benzo(4, 5)cyclohepta(1, 2-b)thiophene which inhibit ovulation and the secretion of luteinizing hormone (LH) in the rat. We also describe the relationship between the structure and activity of these compounds.     

Successive clutches induced by surgical excision of post-ovulatory oocytes in the lizard Cnemidophorus uniparens.

19 animals had eggs excised from the oviducts soon after ovulation. Number of clutches was nearly tripled in excised animals as compared to controls. An influence of eggs in the oviduct on number of clutches is suggested and may indicate a neuronal link between oviduct and hypothalamus.     

Inhibition of ovulation in rats by antagonists to serotonin and by a new tricyclic compound.

The ovulation inhibiting activity in adult rats of the 5HT-antagonists cyproheptadine, mianserin and methysergide is shown. Furthermore the activity of a newly synthetized Cycloheptathiophenederivative, compound 26-921, which inhibits LH-secretion and consequently ovulation, is described.     

Long-term incubation with mifepristone (MLTI) increases the spine density in developing Purkinje cells: new insights into progesterone receptor mechanisms

Cerebellar Purkinje cells (PC) physiologically reveal an age-dependent expression of progesterone with high endogenous concentrations during the neonatal period. Even if progesterone has been previously shown to induce spinogenesis, dendritogenesis and synaptogenesis in immature PC, data about the effects of progesterone on mature PC are missing, even though they could be of significant therapeutic interest. The current study demonstrates for the first time a progesterone effect, depending on the developmental age of PC. Comparable with the physiological course of the progesterone concentration, experimental treatment with progesterone for 24 h achieves the highest effects on the dendritic tree during the early neonate, inducing an highly significant increase in dendritic length, spine number and spine area, while spine density in mature PC could not be further stimulated by progesterone incubation. Observed progesterone effects are certainly mediated by classical progesterone receptors, as spine area and number were comparable to controls when progesterone incubation was combined with mifepristone (incubation for 24 h), an antagonist of progesterone receptors A and B (PR-A/PR-B). In contrast, an increase in the spine number and area of both immature and mature PC was detected when slice cultures were incubated with mifepristone for more than 72 h (mifepristone long-time incubation, MLTI). By including time-lapse microscopy, electron microscopic techniques, PCR, western blot, and MALDI IMS receptor analysis, as well as specific antagonists like trilostane and AG 205, we were able to detect the underlying mechanism of this diverging mifepristone effect. Thus, our results provide new insights into the function and signaling mechanisms of the recently described progesterone receptor membrane component 1 (PGRMC1) in PC. It is highly suitable that progesterone does not just induce effects by the well-known genomic mechanisms of the classical progesterone receptors but also acts through PGRMC1 mediated non-genomic mechanisms. Thus, our results provide first proofs for a previously discussed progesterone-dependent induction of neurosteroidogenesis in PC by interaction with PGRMC1. But while genomic progesterone effects mediated through classical PR-A and PR-B seem to be restricted to the neonatal period of PC, PGRMC1 also transmits signals by non-genomic mechanisms like regulation of the neurosteroidogenesis in mature PC. Thus, PGRMC1 might be an interesting target for future clinical studies and therapeutic interventions.     

Circadian variation in urinary melatonin in clinically healthy women in Japan and the United States of America.

Urinary melatonin excretion is lower in East-Asian (Japanese) than in North-American (whites of mixed ethnic origin) women. Moreover, a statistically significant circadian rhythm is demonstrated by population-mean cosinor in the data pool from both groups of women. Furthermore, statistical significance characterizes interactions of effects from geographic differences (between ethnic groups) with temporal factors. Such spatio-temporal interactions await further scrutiny with a view inter alia of carcinogenesis as it is influenced by a spectrum of intermodulating rhythms.