Assessment of the role of transcript for GATA-4 as a marker of unfavorable outcome in human adrenocortical neoplasms

Abstract Background Malignant neoplasia of the adrenal cortex is usually associated with very poor prognosis. When adrenocortical neoplasms are diagnosed in the early stages, distinction between carcinoma and adenoma can be very difficult to accomplish, since there is yet no reliable marker to predict tumor recurrence or dissemination. GATA transcription factors play an essential role in the developmental control of cell fate, cell proliferation and differentiation, organ morphogenesis, and tissue-specific gene expression. Normal mouse adrenal cortex expresses GATA-6 while its malignant counterpart only expresses GATA-4. The goal of the present study was to assess whether this reciprocal change in the expression of GATA factors might be relevant for predicting the prognosis of human adrenocortical neoplasms. Since human adrenal cortices express luteinizing hormone (LH/hCG) receptor and the gonadotropins are known to up-regulate GATA-4 in gonadal tumor cell lines, we also studied the expression of LH/hCG receptor. Methods We conducted a study on 13 non-metastasizing (NM) and 10 metastasizing/recurrent (MR) tumors obtained from a group of twenty-two adult and pediatric patients. The expression of GATA-4, GATA-6, and LH/hCG receptor (LHR) in normal and tumoral human adrenal cortices was analysed using reverse transcriptase-polymerase chain reaction (RT-PCR) complemented by dot blot hybridization. Results Messenger RNA for GATA-6 was detected in normal adrenal tissue, as well as in the totality of NM and MR tumors. GATA-4, by its turn, was detected in normal adrenal tissue, in 11 out of 13 NM tumors, and in 9 of the 10 MR tumors, with larger amounts of mRNA found among those presenting aggressive clinical behavior. Transcripts for LH receptor were observed both in normal tissue and neoplasms. A more intense LHR transcript accumulation was observed on those tumors with better clinical outcome. Conclusion Our data suggest that the expression of GATA-6 in human adrenal cortex is not affected by tumorigenesis. GATA-4 expression is more abundant in MR tumors, while NM tumors express more intensely LHR. Further studies with larger cohorts are needed to test whether relative expression levels of LHR or GATA-4 might be used as prognosis predictors.

Prostaglandin treatment at the onset of norgestomet and estradiol-based synchronization protocols did not alter the ovarian follicular dynamics or pregnancy per timed artificial insemination in cyclic Bos indicus heifers

The aim of the present study was to evaluate the effects of the PGF2˛treatment givenat the onset of a synchronization of ovulation protocol using a norgestomet (NORG) earimplant on ovarian follicular dynamics (Experiment 1) and pregnancy per AI (P/AI; Exper-iment 2) in cyclic (CL present) Bos indicus heifers. In Experiment 1, a total of 46 heiferswere presynchronized using two consecutive doses of PGF2˛12 days apart. At first dayof the synchronization protocol the heifers received implants containing 3 mg of NORGand 2 mg of estradiol benzoate (EB). At the same time, heifers were randomly assignedto receive 150 mg of d-cloprostenol (n = 23; PGF2˛) or no additional treatment (n = 23;Control). When the ear implants were removed 8 days later, all heifers received a PGF2˛treatment and 1 mg of EB was given 24 h later. The follicular diameter and interval toovulation were determined by transrectal ultrasonography. No effects of PGF2˛treat-ment on the diameter of the largest follicle present were observed at implant removal(PGF2˛= 9.8 ± 0.4 vs. Control = 10.0 ± 0.3 mm; P = 0.73) or after 24 h (PGF2˛= 11.1 ± 0.4 vs.Control = 11.0 ± 0.4 mm; P = 0.83). No differences in the time of ovulation after ear implantremoval (PGF2˛= 70.8 ± 1.2 vs. Control = 73.3 ± 0.9 h; P = 0.10) or in the ovulation rate(PGF2˛= 87.0 vs. Control = 82.6%; P = 0.64) between treatments were observed. In Experi-ment 2, 280 cyclic heifers were synchronized using the same experimental design describedabove (PGF2˛; n = 143 and Control; n = 137), at random day of the estrous cycle. All heifersreceived 300 IU of equine chorionic gonadotropin (eCG) and 0.5 mg of estradiol cypionate(as ovulatory stimulus) when the NORG ear implants were removed. Timed artificial insem-ination (TAI) was performed 48 h after implant removal and the pregnancy diagnosis wasconducted 30 days later. No effects on the P/AI due to PGF2˛treatment were observed(PGF2˛= 51.7 vs. Control = 57.7%; P = 0.29). In conclusion, PGF2˛treatment at the onset ofNORG-based protocols for the synchronization of ovulation did not alter the ovarian follic-ular responses or the P/AI in cyclic Bos indicus beef heifers synchronized for TAI.

Effects of two estradiol esters (benzoate and cypionate) on the induction of synchronized ovulations in Bos indicus cows submitted to a timed artificial insemination protocol

The effects of estradiol benzoate (EB) and estradiol cypionate (EC) on induction of ovulation after a synchronized LH surge and on fertility of Bos indicus females submitted to timed AI (TAI) were evaluated. In Experiment 1, ovariectomized Nelore heifers were used to evaluate the effect of EB (n = 5) and EC (n = 5) on the circulating LH profile. The LH surge timing (19.6 and 50.5 h; P = 0.001), magnitude (20.5 and 9.4 ng/mL; P = 0.005), duration (8.6 and 16.5 h; P = 0.001), and area under the LH curve (158.6 and 339.4 ng/mL; P = 0.01) differed between the EB and EC treatments, respectively. In Experiment 2 (follicular responses; n = 60) and 3 (pregnancy per AI; P/AI; n = 953) suckled Bos indicus beef cows submitted to an estradiol/progesterone-based synchronization protocol were assigned to receive one of two treatments to induce synchronized ovulation: 1 mg of EB im 24 h after progesterone (P4) device removal or 1 mg of EC im at P4 device removal. There was no difference (P > 0.05) between EB and EC treatments on follicular responses (maximum diameter of the ovulatory follicle, 13.1 vs. 13.9 mm; interval from progesterone device removal to ovulation, 70.2 vs. 68.5 h; and ovulation rate, 77.8 vs. 82.8%, respectively). In addition, P/AI was similar (P < 0.22) between the cows treated with EB (57.5%; 277/482) and EC (61.8%; 291/471). In conclusion, despite pharmacologic differences, both esters of estradiol administered either at P4 device removal (EC) or 24 h later (EB) were effective in inducing an LH surge which resulted in synchronized ovulations and similar P/AI in suckled Bos indicus beef cows submitted to TAI. (C) 2012 Elsevier Inc. All rights reserved.

Subclinical impairment of ovarian reserve in juvenile systemic lupus erythematosus after cyclophosphamide therapy

Objective To perform systematic assessment of ovarian reserve markers using a combination of tests in juvenile systemic lupus erythematosus (JSLE) patients without amenorrhoea. Methods Twenty-seven consecutive JSLE female patients and 13 healthy controls without amenorrhoea were evaluated for 6 months. Ovarian reserve was assessed during early follicular phase by serum levels of follicle stimulating hormone (FSH), luteinising hormone (LH), estradiol, inhibin A, inhibin B and anti-Mullerian hormone (AMH). Ovarian size was measured by abdominal ultrasonography. Demographic data, disease activity, damage and treatment were also analysed. Results The median of current age was similar in ISLE patients and controls (16.5 vs. 15years, p=0.31) with a significantly higher age at menarche (13 vs. 12years, p=0.03). A trend of lower median total antral follicle count was observed in JSLE compared to controls (9 vs. 14.5, p=0.062) with similar median of other ovarian reserve parameters (p>0.05). Further evaluation of patients treated with cyclophosphamide and those without this treatment revealed a higher median FSH levels (6.4 vs. 4.6 IU/L, p=0.023). Inhibin B, AMH levels and ovarian volume were also lower but did not reach statistical significance (10.8 vs. 27.6 pg/mL, p=0.175; 0.6 vs. 1.5 ng/mL, p=0.276; 3.4 vs. 5 cm(3), p=0.133; respectively). LH (2.7 vs. 2.9 IU/L, p=0.43), estradiol (50 vs. 38 pg/mL, p=0.337) and inhibin A (1.1 vs. 0 pg/mL, p=0.489) levels were comparable in both groups. Conclusions Our study suggests that ovarian reserve after cyclophosphamide treatment may be hampered in spite of the presence of menstrual cycles emphasising the relevance of gonadal protection during the use of this alkylating agent.

Single-cell expression analysis of BMP15 and GDF9 in mature oocytes and BMPR2 in cumulus cells of women with polycystic ovary syndrome undergoing controlled ovarian hyperstimulation

To detect expression of bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) in oocytes, and their receptor type 2 receptor for BMPs (BMPR2) in cumulus cells in women with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF), and determine if BMPR2, BMP15, and GDF9 expression correlate with hyperandrogenism in FF of PCOS patients. Prospective case-control study. Eighteen MII-oocytes and their respective cumulus cells were obtained from 18 patients with PCOS, and 48 MII-oocytes and cumulus cells (CCs) from 35 controls, both subjected to controlled ovarian hyperstimulation (COH), and follicular fluid (FF) was collected from small (10-14 mm) and large (> 18 mm) follicles. RNeasy Micro Kit (Qiagen(A (R))) was used for RNA extraction and gene expression was quantified in each oocyte individually and in microdissected cumulus cells from cumulus-oocyte complexes retrieved from preovulatory follicles using qRT-PCR. Chemiluminescence and RIA assays were used for hormone assays. BMP15 and GDF9 expression per oocyte was higher among women with PCOS than the control group. A positive correlation was found between BMPR2 transcripts and hyperandrogenism in FF of PCOS patients. Progesterone values in FF were lower in the PCOS group. We inferred that BMP15 and GDF9 transcript levels increase in mature PCOS oocytes after COH, and might inhibit the progesterone secretion by follicular cells in PCOS follicles, preventing premature luteinization in cumulus cells. BMPR2 expression in PCOS cumulus cells might be regulated by androgens.

Ovarian response of Suffolk ewes to estrous synchronization using short-term protocol

The efficacy of estrus synchronization using short-term protocol was evaluated by ultrasound exams in Suffolk ewes during the pre-breeding season. The control Group (n = 12) was synchronized by treatment for 12 days with vaginal sponges impregnated with medroxyprogesterone acetate, and 400 IU eCG at sponge withdrawal. Experimental groups I, II and III kept the sponge in place for 4 days, and 100 µg of PGF2a was administered at sponge withdrawal. Additionally, Group I (n = 12) had 0.1 mg of estradiol benzoate (EB) administered during sponge placement and 50 µg of GnRH 48 hours after sponge removal. Group II (n = 6) had 35 mg of progesterone (P4) injected, and 0.1 mg of EB administered during sponge placement, 400 IU eCG at withdrawal and 48 hours after, 50 µg GnRH were administrated. Group III (n = 12) had 35 mg of P4 and 0.2 mg of EB administered at sponge placement, 400 IU eCG at withdrawal, and 50 µg of GnRH was administrated after 56 hours. Ovaries were monitored through ultrasound scanning. Concerning the first wave, no difference was detected between the control group and the experimental groups. However, the characteristics of ovulatory wave were significantly different between the groups. The duration of the follicular wave was shorter for Group III than for Group II. The follicle in Group I reached its maximum diameter before the Group II. The diameter of the follicle at the sponge withdrawal in the control group was larger than in Group I. After sponge withdrawal, the follicular growth rate was smaller in the control group than in Group III. The maximum diameter of the follicle in Group II was larger than in the other groups. The short-term protocol in which estrogen was used did not synchronize the emergence of the wave of follicular development.

Luteal function and follicular growth following follicular aspiration during the peri-luteolysis period in bos indicus and crossbred cattle

Follicular estradiol triggers luteolysis in cattle. Therefore, the control of follicle growth and steroidogenesis is expected to modulate luteal function and might be used as an anti-luteolytic strategy to improve embryo survival. Objectives were to evaluate follicular dynamics, plasma concentrations of estradiol and luteal lifespan in Bos indicus and crossbred cows subjected to sequential follicular aspirations. From D13 to D25 of a synchronized cycle (ovulation = D1), Nelore or crossbred, non-pregnant and non-lactating cows were submitted to daily ultrasound-guided aspiration of follicles >6 mm (n = 10) or to sham aspirations (n = 8). Diameter of the largest follicle on the day of luteolysis (7.4 +/- 1.0 vs 9.7 +/- 1.0 mm; mean +/- SEM), number of days in which follicles >6 mm were present (2.3 +/- 0.4 vs 4.6 +/- 0.5 days) and daily mean diameter of the largest follicle between D15 and D19 (6.4 +/- 0.2 vs 8.5 +/- 0.3 mm) were smaller (p <0.01) in the aspirated group compared with the control group, respectively. Aspiration tended to reduce (p< 0.10) plasma estradiol concentrations between D18 and D20 (2.95 +/- 0.54 vs 4.30 +/- 0.55 pg/ml). The luteal lifespan was similar (p > 0.10) between the groups (19.6 +/- 0.4 days), whereas the oestrous cycle was longer (p <0.01) in the aspirated group (31.4 +/- 1.2 vs 21.2 +/- 1.3 days). Hyperechogenic structures were present at the sites of aspiration and were associated with increase in concentration of progesterone between luteolysis and oestrus. It is concluded that follicular aspiration extended the oestrous cycle and decreased the average follicular diameter on the peri-luteolysis period but failed to delay luteolysis.

Ovarian and PGF2 alpha responses to stimulation of endogenous PRL pulses during the estrous cycle in mares

The effects of a PRL-stimulating substance (sulpiride) on PRL and PGF2 alpha secretion and on luteal and ovarian follicular dynamics were studied during the estrous cycle in mares. A control group (n = 9) and a sulpiride group (Sp; n = 10) were used. Sulpiride (25 mg) was given every 8 h from Day 13 postovulation to the next ovulation. Repeated sulpiride treatment did not appear to maintain PRL concentrations at 12-h intervals beyond Day 14. Therefore, the hypothesis that a long-term increase in PRL altered luteal and follicular end points was not testable. Hourly samples were collected from the hour of a treatment (Hour 0) to Hour 8 on Day 14. Concentrations of PRL increased to maximum at Hour 4 in the Sp group. The PRL pulses were more prominent (P < 0.008) in the sulpiride group (peak, 19.4 +/- 1.9 ng/mL; mean +/- SEM) than in the controls (11.5 +/- 1.8 ng/mL). Concentrations of a metabolite of PGF2a (PGFM), number, and characteristics of PGFM pulses, and concentrations of progesterone during Hours 0 to 8 were not affected by the increased PRL. A novel observation was that the peak of a PRL pulse occurred at the same hour or 1 h later than the peak of a PGFM pulse in 8 of 8 PGFM pulses in the controls and in 6 of 10 pulses in the Sp group (P < 0.04), indicating that sulpiride interfered with the synchrony between PGFM and PRL pulses. The hypothesis that sulpiride treatment during the equine estrous cycle increases concentrations of PRL and the prominence of PRL pulses was supported. (c) 2012 Elsevier Inc. All rights reserved.

Hormone-regulated expression and distribution of versican in mouse uterine tissues

Abstract Background Remodeling of the extracellular matrix is one of the most striking features observed in the uterus during the estrous cycle and after hormone replacement. Versican (VER) is a hyaluronan-binding proteoglycan that undergoes RNA alternative splicing, generating four distinct isoforms. This study analyzed the synthesis and distribution of VER in mouse uterine tissues during the estrous cycle, in ovariectomized (OVX) animals and after 17beta-estradiol (E2) and medroxyprogesterone (MPA) treatments, either alone or in combination. Methods Uteri from mice in all phases of the estrous cycle, and animals subjected to ovariectomy and hormone replacement were collected for immunoperoxidase staining for versican, as well as PCR and quantitative Real Time PCR. Results In diestrus and proestrus, VER was exclusively expressed in the endometrial stroma. In estrus and metaestrus, VER was present in both endometrial stroma and myometrium. In OVX mice, VER immunoreaction was abolished in all uterine tissues. VER expression was restored by E2, MPA and E2+MPA treatments. Real Time PCR analysis showed that VER expression increases considerably in the MPA-treated group. Analysis of mRNA identified isoforms V0, V1 and V3 in the mouse uterus. Conclusion These results show that the expression of versican in uterine tissues is modulated by ovarian steroid hormones, in a tissue-specific manner. VER is induced in the myometrium exclusively by E2, whereas MPA induces VER deposition only in the endometrial stroma.

Melatonin reduces LH, 17 beta-estradiol and induces differential regulation of sex steroid receptors in reproductive tissues during rat ovulation

Abstract Background Melatonin is associated with direct or indirect actions upon female reproductive function. However, its effects on sex hormones and steroid receptors during ovulation are not clearly defined. This study aimed to verify whether exposure to long-term melatonin is able to cause reproductive hormonal disturbances as well as their role on sex steroid receptors in the rat ovary, oviduct and uterus during ovulation. Methods Twenty-four adult Wistar rats, 60 days old (+/- 250 g) were randomly divided into two groups. Control group (Co): received 0.9% NaCl 0.3 mL + 95% ethanol 0.04 mL as vehicle; Melatonin-treated group (MEL): received vehicle + melatonin [100 μg/100 g BW/day] both intraperitoneally during 60 days. All animals were euthanized by decapitation during the morning estrus at 4 a.m. Results Melatonin significantly reduced the plasma levels of LH and 17 beta-estradiol, while urinary 6-sulfatoximelatonin (STM) was increased at the morning estrus. In addition, melatonin promoted differential regulation of the estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR) and melatonin receptor (MTR) along the reproductive tissues. In ovary, melatonin induced a down-regulation of ER-alpha and PRB levels. Conversely, it was observed that PRA and MT1R were up-regulated. In oviduct, AR and ER-alpha levels were down-regulated, in contrast to high expression of both PRA and PRB. Finally, the ER-beta and PRB levels were down-regulated in uterus tissue and only MT1R was up-regulated. Conclusions We suggest that melatonin partially suppress the hypothalamus-pituitary-ovarian axis, in addition, it induces differential regulation of sex steroid receptors in the ovary, oviduct and uterus during ovulation.

Estradiol induces transcriptional and posttranscriptional modifications in versican expression in the mouse uterus

We have previously shown the differential expression of versican in the mouse uterus under ovarian hormone influence. We also demonstrated there is not a direct correlation between mRNA levels and protein expression, suggesting posttranscriptional events, such as alteration in mRNA stability. This posttranscriptional effect may result in the elongation and stabilization of transcripts poly(A) tail. Thus, the aim of this study was to analyze whether estradiol (E2) regulates versican mRNA stability and expression in a dose-related and time-dependent manner. For this purpose female mice were ovariectomized and treated with a single injection of 0.1 or 10 μg E2. To block transcription a group of females received a single injection of alpha-amanitin before hormone administration. Uterine tissues were collected 30 min, 1, 3, 6, 12 and 24 h after treatments and processed for quantitative real time PCR (qPCR), RACE-PAT Assay and immunohistochemistry. qPCR showed that versican mRNA levels are higher than control from 3 to 24 h after E2 administration, whereas after transcription inhibition versican mRNA unexpectedly increases within 3 h, which can be explained when transcriptional blockers alter the degradation rate of the transcript, resulting in the superinduction of this mRNA. Accordingly, analysis of versican transcript poly(A) tail evidenced a longer product 3 h after treatment, but not after 12 h. Versican immunoreaction becomes conspicuous in the superficial stroma only 3 h after E2 injection, whereas the whole stroma is immunoreactive from 6 h onward. These results demonstrate that E2 modulates versican at the transcriptional and posttranscriptional levels in a time-dependent manner.

Dynamics of follicular growth and progesterone concentrations in cyclic and anestrous suckling Nelore cows (Bos indicus) treated with progesterone, equine chorionic gonadotropin, or temporary calf removal

The objective of this study was to investigate the effects of eCG and temporary calf removal (TCR) associated with progesterone (P4) treatment on the dynamics of follicular growth, CL size, and P4 concentrations in cyclic (n ¼ 36) and anestrous (n ¼ 30) Nelore cows. Cyclic (C) and anestrous (A) cows were divided into three groups. The control group received 2 mg of estradiol benzoate via intramuscular (IM) injection and an intravaginal device containing 1.9 g of P4 on Day 0. On Day 8, the device was removed, and the animals received 12.5 mg of dinoprost tromethamine IM. After 24 hours, the animals received 1 mg of estradiol benzoate IM. In the eCG group, cows received the same treatment described for the control group but also received 400 UI of eCG at the time of device removal. In the TCR group, calves were separated from the cows for 56 hours after device removal. Ultrasound exams were performed every 24 hours after device removal until the time of ovulation and 12 days after ovulation to measure the size of the CL. On the same day as the CL measurement, blood was collected to determine the plasma P4 level. Statistical analyses were performed with a significance level of P ≤ 0.05. In cyclic cows, the presence of the CL at the beginning of protocol resulted in a smaller follicle diameter at the time of device removal (7.4 ± 0.3 mm in cows with CL vs. 8.9 ± 0.4 mm in cows without CL; P ¼ 0.03). All cows ovulated within 72 hours after device removal. Anestrous cows treated with eCG or TCR showed follicle diameter at fixed-timed artificial insemination (A-eCG 10.2 ± 0.3 and A-TCR 10.3 ± 0.5 mm) and follicular growth rate (A-eCG 1.5 ± 0.2 and A-TCR 1.3 ± 0.1 mm/day) similar to cyclic cows (C-eCG 11.0 ± 0.6 and C-TCR 12.0 ± 0.5 mm) and (C-eCG 1.4 ± 0.2 and C-TCR 1.6 ± 0.2 mm/day, respectively; P ≤ 0.05). Despite the similarities in CL size, the average P4 concentration was higher in the A-TCR (9.6 ± 1.4 ng/mL) than in the A-control (4.0 ± 1.0 ng/mL) and C-TCR (4.4 ± 1.0 ng/mL) groups (P < 0.05). From these results, we conclude that eCG treatment and TCR improved the fertility of anestrous cows by providing follicular growth rates and size of dominant follicles similar to cyclic cows. Additionally, TCR increases the plasma concentrations of P4 in anestrous cows

Reproductive biology of the ghost shrimp Lepidophthalmus bocourti (A. Milne-Edwards, 1870) (Decapoda: Axiidea: Callianassidae): A tropical species with a seasonal reproduction

Based on the hypothesis that reproduction is a continuous process in tropical habitats, we analysed reproductive periodicity and egg production in the callianassid ghost shrimp Lepidophthalmus bocourti, one of the most common species in mangrove systems along the Pacific coast of Central America. During one year (May 2008 to April 2009), individuals of L. bocourti (N = 499) were collected nearshore Gulf of Nicoya, Pacific coast of Costa Rica. Observations were made on presence or absence of incubated embryos, and gonad activity of females was analysed as gonadosomatic index (GSI). Our results revealed that L. bocourti has a marked seasonal breeding period, which contradicts previous reports regarding coastal marine decapods from the tropics. Ovigerous females were found only from June to August, while high GSI values were obtained from March to July. The increase of GSI and appearance of ovigerous females were associated with a concomitant decrease of salinity, but not with temperature. We assume that reproduction of L. bocourti is adapted to local changes of environmental conditions, and that a decrease in salinity during rainy season may serve as a triggering factor for ovarian development. Compared to other ghost shrimps, L. bocourti produced on average more (2002 +/- 1365) and smaller (0.87 +/- 0.109 mm) eggs, which seems to suggest that this species does not have an abbreviated larval development as reported for other species of genus. The deviation from the generalization of constant reproduction in the tropics for shallow water marine invertebrates and its probable cause are adequately discussed.

VIP expression in vessels of the vaginal wall: relationship with estrogen status

Objective Vasoactive intestinal peptide (VIP) is a neuropeptide with elevated expression in regions that control urogenital functions. Estrogen appears to modulate VIP expression in various organs, but this effect has not been demonstrated in the vaginal wall. The aim of this study was to evaluate the influence of estrogen status on VIP expression in vessels of the vaginal wall. Methods Surgical specimens were removed from the vaginal walls of 18 premenopausal women and 12 postmenopausal women who were given surgery for genital prolapse grade I or II. Vaginal specimens were stained with estrogen receptor-alpha (ER-alpha) and VIP antibodies. Levels of follicle stimulating hormone (FSH), estradiol, prolactin, fasting glucose and serum thyroxine stimulating hormone were also measured. Estrogen status was assessed on the basis of FSH and ER-alpha scores. Results The vaginal walls of premenopausal women had significantly higher ER-alpha scores than those of menopausal women (premenopausal group, 3.6 +/- 2.2; menopausal group, 1.4 +/- 1.8; p = 0.01). Premenopausal women also had significantly higher levels of VIP in the vaginal wall than menopausal women (p = 0.02). Increasing age was associated with lower level of VIP staining (odds ratio 0.88; 95% confidence interval 0.78-0.99). Conclusion Levels of ER-alpha and VIP expression in the posterior vaginal wall were higher in premenopausal than in menopausal women, but VIP expression was not associated with estrogen status. Age was an independent predictor of VIP staining in vaginal wall biopsies.

17 beta-Estradiol replacement in young, adult and middle-aged female ovariectomized rats promotes improvement of spatial reference memory and an antidepressant effect and alters monoamines and BDNF levels in memory- and depression-related brain areas

Clinical and experimental evidence suggest that estrogens have a major impact on cognition, presenting neurotrophic and neuroprotective actions in regions involved in such function. In opposite, some studies indicate that certain hormone therapy regimens may provoke detrimental effects over female cognitive and neurological function. Therefore, we decided to investigate how estrogen treatment would influence cognition and depression in different ages. For that matter, this study assessed the effects of chronic 17 beta-estradiol treatment over cognition and depressive-like behaviors of young (3 months old), adult (7 months old) and middle-aged (12 months old) reproductive female Wistar rats. These functions were also correlated with alterations in the serotonergic system, as well as hippocampal BDNF. 17 beta-Estradiol treatment did not influence animals' locomotor activity and exploratory behavior, but it was able to improve the performance of adult and middle-aged rats in the Morris water maze, the latter being more responsive to the treatment. Young and adult rats displayed decreased immobility time in the forced swimming test, suggesting an effect of 17 beta-estradiol also over such depressive-like behavior. This same test revealed increased swimming behavior, triggered by serotonergic pathway, in adult rats. Neurochemical evaluations indicated that 17 beta-estradiol treatment was able to increase serotonin turnover rate in the hippocampus of adult rats. Interestingly, estrogen treatment increased BDNF levels from animals of all ages. These findings support the notion that the beneficial effects of 17 beta-estradiol over spatial reference memory and depressive-like behavior are evident only when hormone therapy occurs at early ages and early stages of hormonal decline. (C) 2011 Elsevier B.V. All rights reserved.