Aquaporin-2 expression in human endometrium correlates with serum ovarian steroid hormones

The aim of the present study was to examine the expression of aquaporin-2 (AQP2), a member of the water channel family aquaporins (AQPs), in human uterine endometrium and its modulation of ovarian steroid hormone at the proliferative and secretory phases. Western blot, immunohistochemistry, and RT-PCR were employed in the present study. Western blot revealed a 29-kDa band that represented AQP2 in human endometrium. The expression of AQP2 in endometrium was confirmed by RT-PCR and immunohistochemical results. The immunohistochemical analysis demonstrated that AQP2 was prominent in luminal and glandular epithelial cells of endometrium. The levels of endometrial AQP2 expression changed during the menstrual cycle and were higher in the secretory endometrium than in the proliferative endometrium. A significantly high level of AQP2 was detected at the mid-secretory phase. There was a positive correlation between the levels of the endometrial AQP2 expression and the concentrations of the serum 17beta-estradiol (E2) or/and progesterone (P4). These data for the first time corroborate that AQP2 is expressed in human endometrium and that the expression of AQP2 in human endometrium might be regulated by E2 or/and P4. The changed expression of AQP2 at different phases of the menstrual cycle may be essential to reproductive physiology in human. The high level of endometrial AQP2 expression was observed at the mid-secretory phase, the time of embryo implantation, suggesting that AQP2 might play physiological roles in the uterine receptivity.     

Effects of 17β-estradiol and progesterone on the production of adipokines in differentiating 3T3-L1 adipocytes: Role of Rho-kinase

Effect of female sex hormones on the production/release of adipocyte-derived cytokines has been debatable. Furthermore, whether the cellular signaling triggered by these hormones involve Rho-kinase has not been investigated yet. Therefore, in this study, effects of 17β-estradiol and progesterone as well as the Rho-kinase inhibitor, Y-27632 on the level of adipokines such as resistin, adiponectin, leptin, TNF-α and IL-6 were investigated in 3T3-L1-derived adipocytes. Differentiation was induced in the post-confluent preadipocytes by the standard differentiation medium (Dulbecco’s modified Eagle’s medium with 10% fetal bovine serum together with the mixture of isobutylmethylxanthine, dexamethasone and insulin) in the presence of 17β-estradiol (10⁻⁸–10⁻⁷ M), progesterone (10⁻⁶–10⁻⁵ M), the Rho-kinase inhibitor, Y-27632 (10⁻⁵ M) and their combination for 8 days. Measurements of the adipokines were performed in the culturing medium by ELISA kits using specific monoclonal antibodies. 17β-estradiol elevated resistin but decreased adiponectin and IL-6 levels; however, it did not alter the concentration of leptin and TNF-α. Y-27632 pretreatment inhibited the rise of resistin and the fall of adiponectin by 17β-estradiol without any effects by its own. Progesterone did not change resistin, leptin and TNF-α level; however, it elevated adiponectin and decreased IL-6 production. Neither 17β-estradiol nor Y-27632 was able to antagonize the increase of adiponectin and the reduction of IL-6 levels by progesterone. While Y-27632 alone lowered IL-6 level, it increased leptin and TNF-α concentration without altering resistin and adiponectin. In conclusion, 17β-estradiol could modify adipokine production in 3T3-L1 adipocytes with the actions some of which involve Rho-kinase mediation.     

Acute estrogen treatment facilitates recognition memory consolidation and alters monoamine levels in memory-related brain areas

Acute effects of estrogens on mnemonic processes were examined at the behavioral and neurochemical levels. 17β-estradiol and 17α-estradiol influences on memory consolidation were assessed using object placement (OP) and object recognition (OR) tasks. Subjects received treatment immediately after a sample trial (exploring two novel objects), and memory of objects (OR memory) or location of objects (OP memory) was tested 4 h later. Both isomers of estradiol enhanced memory. For spatial memory, 15 and 20 µg/kg of 17β-estradiol facilitated OP, while lower and higher doses were ineffective. 17α-estradiol had a similar pattern, but a lower dose was effective. When treatment was delayed until 45 min after a sample trial, memory was not enhanced. For non-spatial memory, OR was facilitated at 5 µg/kg of 17β-estradiol and at 1 and 2 µg/kg of 17α-estradiol and, similar to OP, lower and higher doses were ineffective. These data demonstrate that beneficial effects of estrogens are dose, time and task dependent, and the dose-response pattern is an inverted U. Because monoamines are known to have contributions to memory, brains were removed 30 min after treatment for measurements of dopamine (DA), norepinephrine (NE), serotonin (5-HT), and metabolites. Estrogen elevated 5HT, NE metabolite MHPG, turnover ratio of NE to MHPG, and DA metabolite DOPAC levels in the prefrontal cortex, while NE and MHPG were decreased in the hippocampus. Thus, acute estrogens exert rapid effects on memory consolidation and neural function, which suggests that its mnemonic effects may involve activation of membrane associated estrogen receptors and subsequent signaling cascades, and that monoamines may contribute to this process.     

Changes in ovarian follicles and in vitro sex hormone release in the lizard Podarcis sicula sicula

An in vitro superfusion method was used to test sex hormone release from different kinds of ovarian follicle (growing follicles, postovulatory follicles, and atretic follicles) in the lizard Podarcis sicula sicula. Sex hormone output changes with the stage of follicle evolution and sexual cycle. Previtellogenetic follicles prevail in early-spring quiescent ovaries and secrete mainly progesterone, which is probably utilized at that phase to delay ovarian resumption. In the active ovary, progesterone output from previtellogenetic follicles decreases, whereas vitellogenetic follicles produce a significant amount of 17β-estradiol, which is necessary for sustaining vitellogenin synthesis by the liver and oviduct growth. As follicles become ripe, progesterone production is resumed, and it increases in young postovulatory follicles. This is in line with the functions assigned to the hormone at that phase of the sexual cycle, i.e., the induction of oocyte maturation and the regulation of egg retention in the oviduct. Postovulatory follicles can also synthetize 17β-estradiol. After oviposition, this hormone, which is secreted by the old postovulatory follicles, can reinitiate vitellogenin synthesis, allowing the development of a new oocyte set. Our data confirm that active, although ephemeral, corpora lutea are also formed in oviparous species. A limited contribution to ovarian sex steroid production derives also from atretic follicles, at least at the early stages of the breeding cycle. © 1993 Wiley-Liss, Inc.     

Follicular 17β-estradiol and progesterone concentrations and degree of cumulus cell expansion as predictors of in vivo-matured oocyte developmental competence in superstimulated heifers

The quality of an oocyte is crucial for successful generation of offspring, but few selection parameters have been identified that reliably predict oocyte developmental competence. The objective of the present study was to determine whether the developmental competence of in vivo-matured oocytes derived from superstimulated heifers could be predicted by 17β-estradiol and progesterone concentrations in follicular fluid, degree of cumulus cell expansion, and follicular diameter. Cumulus oocyte complexes were individually collected from follicles ≥8 mm 22 hours after an induced LH peak and individually fertilized and cultured in vitro. Only oocytes that originated from follicles with 17β-estradiol ≤0.25 μM and progesterone ≥0.26 μM developed into blastocysts. When a combination of these cutoff values was evaluated as a predictor of oocyte competence, the sensitivity, specificity, positive predictive value, and negative predictive value were 100%, 75%, 49%, and 100%, respectively. Hormone concentrations in follicular fluid were also associated with the degree of cumulus cell expansion and only cumulus oocyte complexes with full expansion developed into blastocysts; sensitivity, specificity, positive predictive value, and negative predictive value were 100%, 71%, 45%, and 100%, respectively, when full expansion was used as the predictive criterion for blastocyst production. Follicular diameter was not a good predictor of oocyte competence. In conclusion, concentrations of 17β-estradiol and progesterone in the preovulatory follicle and the degree of cumulus cell expansion are predictors of blastocyst production in superstimulated heifers and can be used as selection markers for oocyte developmental competency.     

Sex differences in neuroactive steroid levels in the nervous system of diabetic and non-diabetic rats

Neuropathy and encephalopathy represent important complications of diabetes. Recent observations obtained in experimental models have suggested that, in male rats, neuroactive steroids are protective agents and that their levels in peripheral (PNS) and central (CNS) nervous system are strongly affected by the disease.It is interesting to highlight that incidence, progression and severity of diabetic neuropathy and diabetic encephalopathy are different in the two sexes. Consequently, it is important to determine the changes in neuroactive steroid levels in the PNS and the CNS of both males and females. To this aim, we have evaluated the levels of neuroactive steroids such as, pregnenolone, progesterone and its metabolites, testosterone and its metabolites, and dehydroepiandrosterone in different CNS regions (i.e., cerebral cortex, cerebellum and spinal cord) and in the sciatic nerve of control and diabetic (i.e., induced by streptozotocin) male and female rats. Data obtained by liquid chromatography-tandem mass spectrometry indicate that the levels of neuroactive steroids show sex and regional differences in control animals. Streptozotocin-induced diabetes resulted in a strong general decrease in neuroactive steroid levels, in both the PNS and the CNS. In addition, the effects of diabetes on neuroactive steroid levels also show sex and regional differences.These findings may have strong implications for the development of new sex-oriented therapies for the treatment of diabetic neuropathy and diabetic encephalopathy, based on the use of neuroactive steroids.     

Celery oil modulates DEHP-induced reproductive toxicity in male rats

The objective of the study was to investigate the protective effect of Apium graveolens (AP) against di-(2-ethylhexyl) phthalate (DEHP)-induced testes injury in rats. Adult rats were divided into nine groups: (1) control group (no treatment); (2) corn oil (60 μg/kg body weight – bwt); (3) AP (50 μg/kg bwt); (4) 300 mg DEHP/kg bwt; (5) 500 mg DEHP/kg bwt; (6) 1000 mg DEHP/kg bwt; (7) 300 mg DEHP/kg bwt + AP; (8) 500 mg DEHP/kg bwt + AP; and (9) 1000 mg DEHP/kg bwt + AP. Oral administration of treatments was performed daily for 6 weeks. DEHP decreased (p < 0.01) body weight, testis weight and serum concentrations of testosterone, cholesterol and total proteins. Moreover, DEHP increased (p < 0.001) total antioxidant capacity in the testis and plasma DEHP level. In addition, DEHP decreased mRNA expression of two testicular steroidogenic enzymes: 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase. DEHP also caused atrophy, vacuolar degeneration and aspermia of the seminiferous tubules. AP administered concurrently with DEHP effectively alleviated most of the DEHP-induced effects. In conclusion, in male rats, DEHP had adverse effects on the testis including inhibition of androgen production. A concurrent administration of A. graveolens (celery oil) protected the testis against DEHP-induced toxicity.     

Effects of testosterone and 17-beta-estradiol on TNF-alpha-induced E-selectin and VCAM-1 expression in endothelial cells. Analysis of the underlying receptor pathways

This study investigated the effects of testosterone and 17-beta-estradiol on tumor necrosis factor-alpha (TNF-alpha)-induced endothelial expression of E-selectin and vascular cell adhesion molecule-1 (VCAM-1) and the potential roles of hormone receptors involved in these actions. Human umbilical vein endothelial cells (HUVEC) were stimulated with TNF-alpha in the presence or absence of testosterone or 17-beta-estradiol, and the expression of E-selectin and VCAM-1 was investigated. As shown by Western blot analysis, co-administration with testosterone or 17-beta-estradiol increased the expression of E-selectin and VCAM-1 induced by TNF-alpha at 6 h and 3 h, respectively. Similarly, RT-PCR analysis revealed a significant increase in the amount of mRNA for E-selectin and VCAM-1 after co-administration with testosterone or 17-beta-estradiol in TNF-alpha-stimulated HUVEC. The presence of mRNA and proteins for androgen receptor and estrogen receptor alpha in HUVEC was verified by RT-PCR and Western blot. Flow cytometric analysis showed that preincubation with androgen receptor antagonist cyproterone and estrogen receptor antagonist tamoxifen completely abrogated the upregulating effects of testosterone and 17-beta-estradiol on TNF-alpha-induced E-selectin and VCAM-1 expression, respectively. Expression of TNF receptors in TNF-alpha-stimulated HUVEC was not influenced by testosterone and 17-beta-estradiol. The data indicate that both testosterone and 17-beta-estradiol increase TNF-alpha-induced E-selectin and VCAM-1 expression in endothelial cells via a receptor-mediated system, and expression of TNF receptors are not changed in these actions. The implications of these results for the facilitory effects of both sex hormones on immune reactions are discussed.     

Changes in the Mutagenic and Estrogenic Activities of 17β-Estradiol after Treatment with Nitrite

We determined the changes in the mutagenic and estrogenic activities of 17β-estradiol after a nitrite treatment. Nitrite-treated 17β-estradiol showed mutagenic activities toward Salmonella typhimurium strains TA 100 and TA 98. We confirmed that nitrite-treated 17β-estradiol generated radicals from the results of an analysis of electron spin resonance. By applying an instrumental analysis, we identified 2-nitro-17β-estradiol to have been formed in the reaction mixture. 2-Nitro-17β-estradiol did not exhibit mutagenic activities toward Salmonella typhimurium strains, suggesting that other mutagens might have been formed in the reaction mixture. The clastogenic properties of nitrite-treated 17β-estradiol and 2-nitro-17β-estradiol were analyzed by a micronucleus test with male ICR mice. Nitrite-treated 17β-estradiol and 2-nitro-17β-estradiol induced a significantly higher frequency of micronucleated reticulocytes in mice. The estrogenic activity of 2-nitro-17β-estradiol was found to be lower than that of 17β-estradiol. These data suggest that a daily oral intake of 17β-estradiol and nitrite might induce the formation of mutagenic compounds in our body.     

Sex steroids in plasma of lake whitefish Coregonus clupeaformis during spawning in Lake Erie

Lake whitefish, Coregonus clupeaformis, were collected from the Western basin of Lake Erie during spawning. Free and conjugated (sulfated and glucuronidated) steroids including testosterone (T), 11-ketotestosterone (11-kT), estradiol-17beta (E2) and 17,20beta-dihydroxy-4-pregnen-3-one (17,20betaP) were measured in the plasma by radioimmunoassay. In males, the progression of spermiation was characterized by a significant decrease in plasma free steroids, whereas the levels of conjugated steroids remained similar and low, except for sulfated and glucuronidated testosterone. Plasma sex steroids did not correlate with the density or the motility of the spermatozoa. In females, the concentration of plasma T was significantly higher in preovulating than in ovulating females. The levels of E2 and 17,20betaP in ovulating lake whitefish exhibited large variations ranging from below detection limit to 0.9 ng ml(-1) and from 0.2 to 13 ng ml(-1), respectively. Analysis of conjugated steroids revealed high levels of glucuronidated and sulfated 17,20betaP and glucuronidated T in females ovulating in December. However, no significant differences in the proportion of the conjugated steroids were observed.     

Aglepristone (RU534) administration to non-pregnant bitches in the mid-luteal phase induces early luteal regression

The effect of the antiprogestagen aglepristone (10 mg/kg bw), administered at days 29 and 30 following the estimated day of LH surge (day 0), on corpora lutea (CL) function was examined during the diestrus phase of non-pregnant bitches. Aglepristone shortened (P < 0.01) the luteal phase and complete luteolysis (progesterone <2 ng/mL) was observed at days 40.8 ± 3.5 and 71.5 ± 4.6 (means ± SD; n = 9/group) in treated and control bitches, respectively. Peripheral estradiol-17β concentrations declined from 91.5 ± 14.3 pg/mL at day 9 to 50 pg/mL at day 18, remaining at approximately the same levels thereafter in both treated and control bitches. Intraluteal in vitro synthesis of progesterone and estradiol-17β released by CL explanted at day 38 from control bitches (511.9 ± 285.6 and 40.7 ± 17.2 pg/mg protein, respectively) did not differ from that of treated. From day 38, intraovarian hemodynamic variables (arterial blood flow, systolic peak, and end-diastolic velocities), monitored by color-coded and pulsed Doppler, decreased more steeply (P < 0.01) in aglepristone-treated (n = 4) than in control (n = 4) bitches, whereas the resistance index increased (P < 0.01) in treated animals. All the blood flow parameters were undetectable at 60 ± 3.6 and 68 ± 2.0 days (medians ± SD) after LH peak in treated and control bitches, respectively. In conclusion, aglepristone administration to dogs during the mid-luteal phase markedly accelerates the luteolytic process which is accompanied by a parallel decline in ovarian blood flow supply with a shift from approximately 8 to 10 days.     

Changes in the histomorphology of the canine cervix through the oestrous cycle

The importance of canine reproduction is steadily increasing and little is known about the canine cervix so far. The aim of this study was to describe the histomorphology of the canine cervix and to determine its correlation to the stage of oestrous cycle and to circulating concentrations of progesterone (P4) and estradiol-17beta (E2), respectively. Ovariohysterectomy (OHE) was performed in 33 non-pregnant, healthy, intact bitches in defined stages of oestrous cycle (proestrus N = 5, estrus N = 7, early diestrus N = 5, late diestrus N = 11, anestrus N = 5). The entire cervix was collected for histological evaluation of the epithelial layer (number of layers, thickness), the stroma (number of layers, thickness, density, structure, and distribution of elastic fibres) and the average area and density of cervical glands as well as blood vessels. These parameters were evaluated in all the three parts of the cervix (cranial, middle, and caudal or vaginal part). The cervix showed the typical structure with a superficial epithelium, a lamina propria with cervical glands and vascular structures and a tunica muscularis below. Folds in the superficial epithelium were only observed in 54% females (N = 18). Epithelial thickness (P < 0.0001), number of glands (P < 0.05), mean area of glands (P < 0.0001), mean area of venous vessels (P < 0.0001), number of arterial vessels (P = 0.02), number of mast cells and number of eosinophilic granulocytes per mm² (P < 0.01) were significantly influenced by the stage of cycle. The following factors were significantly influenced by the localisation: number of epithelial layers (P < 0.0001), thickness of stroma (P < 0.0001) and mean number of glands (P < 0.01). Only mean area of venous vessels was significantly influenced by the stage of cycle and the localisation (P < 0.01). Besides, P4 was significantly correlated to number of glands per mm² (P < 0.0001), mean area of venous vessels (P < 000.1) and number of mast cells (P < 0.01).This study provided detailed information about the histomorphological structure of the cervix in non-pregnant bitches and showed that the cervix undergoes cyclic changes during the canine oestrous cycle, in particular in association with circulating progesterone concentration.     

Effect of aluminium on duodenal calcium transport in pregnant and lactating rats treated with bromocriptine

The aim of present work was to study the effect of oral aluminium (Al) overload on intestinal calcium (Ca) absorption in the critical stages of pregnancy and lactation of rats and to find out possible relationships with prolactin (PRL) and 17beta-estradiol (E2) circulating levels. Adult female Wistar rats were orally treated from day 1 of pregnancy with 0 (control), or 50 mg elemental Al (as chloride)/kg body weight per day. Ca transport was determined by everted duodenal sacs technique using 2 microCi of (45)CaCl(2) as flux marker (JCa(ms)). Al treatment reduced JCa(ms) either in late pregnancy (day 19) or in middle lactation (day 9 postpartum). Oral administration of bromocriptine (BrC), an inhibitor of PRL secretion, at dose of 10 mg/kg body weight given 18 h before JCa(ms) measurements were done, produced a significant decrease in the inhibitory effect of Al on JCa(ms), expressed as percent of control, at day 9 of nursing (vehicle: 51+/-7%, BrC: 28+/-4%, P <0.05). A positive correlation between Al effects on JCa(ms) and the physiological variations of E2 serum levels along pregnancy and lactation in BrC-treated rats was also found (r(2)=0.277, P =0.001). We conclude Al could reduce transcellular Ca absorption in the duodenum by interfering with physiological mechanisms of Ca transport partially mediated by serum level increments of E2 and PRL, observed in late pregnancy and mainly during middle lactation of rats.     

Relationships between follicular fluid steroid hormone concentrations, oocyte maturity, in vitro fertilization and embryonic development in the rhesus monkey

Oocytes and matched samples of follicular fluid (FF) were obtained from 70 follicles of five rhesus monkeys stimulated with either pregnant mare serum gonadotropin or human menopausal gonadotropin. Follicular aspiration was performed 30-32 h after human chorionic gonadotropin administration. The concentrations of estradiol (E2), progesterone (P), testosterone (T), and dihydrotestosterone (DHT) in FF were measured. Twenty-six percent of oocytes were classified as mature (M), 41% matured in vitro (Miv), 13% were dysmature, and 20% atretic. M oocytes were associated with significantly higher levels of P and a higher P:E2 ratio. There were no differences in hormone levels associated with fertilized and nonfertilized oocytes. Thirty-five embryos developed to the six- to eight-cell stage in vitro, of which 13 exhibited optimal cleavage rates. Significantly lower levels of E2 and higher P:E2 ratios were associated with the more rapidly cleaving embryos. Proportionally more embryos showing optimal cleavage rates developed from M compared to Miv oocytes, and only embryos derived from M oocytes developed to blastocysts in culture. Optimal cleavage rates to the six- to eight-cell stage in vitro, rather than fertilization rates, are a better indicator of (subsequent) developmental capacity, and, in this study, embryonic development was closely associated with the maturity of the oocyte at recovery.     

Effect of treatment with different doses of 17-beta-estradiol on the insulin receptor

The mechanism for the development of insulin resistance in normal pregnancy is complex and is associated with serum levels of sex hormones. However, the influence of these hormones on the early steps of insulin action has not been extensively studied, although the potentially beneficial effect of estradiol on glucose homeostasis has been reported. In this paper, we attempted to determine the effect of 17-beta-estradiol on the insulin receptor of ovariectomized rats treated with different doses of hormones. Our results showed a tissue-dependent response to estradiol. We found that low doses of estradiol increased the amount of insulin receptors in liver and muscle on days 6 and 11 of treatment but not in adipose tissue, and after 16 days only the muscle responsed in this way. On the other hand, high doses of estradiol significantly decreased the amount of insulin receptors, at least in muscle and adipose tissue. We believe that the low concentrations of 17-beta-estradiol (similar to early pregnancy) could be responsible for the increase in insulin sensitivity by increasing the amount of insulin receptors in peripheral tissues. When the hormone levels were high (similar to late pregnancy) the amount of insulin receptors decreased in peripheral tissues, and insulin sensitivity is diminished just as in late pregnancy. The specific molecular mechanism for this action is as yet unknown.     

Pharmacological characterization of the mechanisms involved in the vasorelaxation induced by progesterone and 17β-estradiol on isolated canine basilar and internal carotid arteries

Progesterone and 17β-estradiol induce vasorelaxation through non-genomic mechanisms in several isolated blood vessels; however, no study has systematically evaluated the mechanisms involved in the relaxation induced by 17β-estradiol and progesterone in the canine basilar and internal carotid arteries that play a key role in cerebral circulation. Thus, relaxant effects of progesterone and 17β-estradiol on KCl- and/or PGF_2α-pre-contracted arterial rings were investigated in absence or presence of several antagonists/inhibitors/blockers; the effect on the contractile responses to CaCl₂ was also determined. In both arteries progesterone (5.6–180 μM) and 17β-estradiol (1.8–180 μM): (1) produced concentration-dependent relaxations of KCl- or PGF_2α-pre-contracted arterial rings; (2) the relaxations were unaffected by actinomycin D (10 μM), cycloheximide (10 μM), SQ 22,536 (100 μM) or ODQ (30 μM), potassium channel blockers and ICI 182,780 (only for 17β-estradiol). In the basilar artery the vasorelaxation induced by 17β-estradiol was slightly blocked by tetraethylammonium (10 mM) and glibenclamide (K_ATP; 10 μM). In both arteries, progesterone (10–100 μM), 17β-estradiol (3.1–31 μM) and nifedipine (0.01–1 μM) produced a concentration-dependent blockade of the contraction to CaCl₂ (10 μM–10 mM). These results suggest that progesterone and 17β-estradiol produced relaxation in the basilar and internal carotid arteries by blockade of L-type voltage dependent Ca²⁺ channel but not by genomic mechanisms or production of cAMP/cGMP. Potassium channels did not play a role in the relaxation to progesterone in both arteries or in the effect of 17β-estradiol in the internal carotid artery; meanwhile K_ATP channels play a minor role on the effect of 17β-estradiol in the basilar artery.     

Influence of different estrogens on neuroplasticity and cognition in the hippocampus

Background

Estrogens modulate the morphology and function of the hippocampus. Recent studies have focused on the effects of different types of estrogens on neuroplasticity in the hippocampus and cognition. There are three main forms of estrogens found in mammals: estradiol, estrone, and estriol. The vast majority of studies have used estradiol to investigate the effects of estrogens on the brain.

Scope of review

This review focuses on the effects of different estrogens on adult hippocampal neurogenesis, synaptic plasticity in the hippocampus, and cognition in female rats.

Major conclusions

Different forms of estrogens modulate neuroplasticity and cognition in complex and intriguing ways. Specifically, estrogens upregulate adult hippocampal neurogenesis (via cell proliferation) and synaptic protein levels in the hippocampus in a time- and dose-dependent manner. Low levels of estradiol facilitate spatial working memory and contextual fear conditioning while high levels of estradiol impair spatial working, spatial reference memory and contextual fear conditioning. In addition, estrone impairs contextual fear conditioning.

General significance

Advances in our knowledge of how estrogens exert their effects on the brain may ultimately lead to refinements in targeted therapies for cognitive impairments at all stages of life. However caution should be taken in interpreting current research and in conducting future studies as estrogens likely work differently in males than in females.     

He-Ne激光照射与雌激素对去卵巢雌兔血液流变性的影响

本实验将卵巢切除后的24只成年雌性兔分为4组,分别为A：卵巢切除组、B：雌激素治疗组、C：He-Ne激光血管内照射组、D：雌激素加He—Ne激光血管内照射组,分别测定其血液粘度等6项血液流变学指标。研究比较雌激素与低强度He—Ne激光血管内照射对去卵巢雌兔血液流变学的影响,为两者对绝经后妇女心血管疾病防治的临床使用提供参考。结果表明：雌激素可改善部分血液流变学指标;激光血管内照射使6项血液流变学指标均明显改善;雌激素加激光血管内照射共同作用与单独用激光血管内照射的结果大致相同。提示临床He—Ne激光血管内照射可阶段性替代雌激素应用于改善血液流变性,以便减少雌激素的剂量,降低其副作用。     

恶臭假单胞菌SJTE-1中氧化17β-雌二醇的17β-羟甾类脱氢酶2及其转录调控因子AraC的鉴定

[目的]假单胞菌SJTE-1可高效转化17β-雌二醇,但其代谢机制尚不清楚。本文鉴定和表征了该菌株中参与雌二醇降解与调控过程的17β-羟甾类脱氢酶2(17β-HSD2)和转录调控因子AraC。[方法]我们通过荧光定量PCR分析了17β-hsd2和araC的转录水平;我们在大肠杆菌BL21(DE3)菌株中异源表达了17β-HSD2和AraC基因,并利用金属离子亲和层析法纯化获得了重组蛋白;我们体外表征了17β-HSD2的酶学性质,利用高效液相色谱鉴定了其产物;通过电泳迁移转移法和DNase酶I足迹试验,我们鉴定了重组蛋白AraC的结合能力与结合位点。[结果]17β-HSD2和AraC可被17β-雌二醇诱导表达;蛋白序列比对结果表明17β-HSD2含有短链脱氢酶/还原酶(SDR)和β-羟甾类脱氢酶的保守结构与残基。该酶以NAD+为辅助因子,在C17位点氧化17β-雌二醇,其Km值为0.082 mmol/L,Vmax值为56.26±0.02μmol/(min·mg);5 min内可转化97.4%以上的雌二醇。转录调控因子AraC可直接结合17β-hsd2基因启动子区的特异位点;雌二醇与雌酮可解除这一结合,启动17β-hsd2基因转录;过表达AraC蛋白可抑制17β-hsd2的转录。[结论]假单胞菌SJTE-1的17β-羟甾类脱氢酶2可高效催化17β-雌二醇转化,并受到转录因子AraC的直接调控。本工作可推进细菌的雌激素降解酶学机制与调控网络研究。