Urinary incontinence: a classification system and treatment protocols for the primary care provider

PURPOSE: To provide nurse practitioners (NPs) with an objective system for classification of urinary incontinence and protocols for treating the condition in the primary care setting. DATA SOURCE: Clinical practice guidelines and the author's clinical experience. CONCLUSIONS: By using tables of classifications of urinary incontinence, management strategies, and protocols, NPs can successfully manage mild urinary incontinence in primary care settings in a cost-effective manner. IMPLICATIONS FOR PRACTICE: A thorough history and objective classification of the severity of incontinence provides the framework for treating urinary incontinence in a methodical and effective manner.     

Anatomical distribution of sex steroid hormone receptors in the brain of female medaka

Estrogen and androgen play crucial roles in coordinating reproductive functions through estrogen receptors (ERs) and androgen receptors (ARs), respectively. These receptors are considered important for regulation of the hypothalamo‐pituitary‐gonadal (HPG) axis. Despite their biological importance, the distribution of sex steroid receptors has not been fully analyzed anatomically in the teleost brain. The teleosts have many characteristic features, which allow unique approaches toward an understanding of the regulatory mechanisms of reproductive functions. Medaka serves as a good model system for studying the mechanisms by which steroid receptor‐mediated systems are regulated, because 1) their breeding conditions can be easily manipulated; 2) we can take advantage of the genome database; and 3) molecular genetic tools, such as transgenic techniques, are applicable. We analyzed the distribution of ERα, ERβ1, ERβ2, ARα, and ARβ mRNA by in situ hybridization in the brain of female medaka. We found that all subtypes of ERs and ARs were expressed in the following nuclei: the dorsal part of the ventral telencephalic area (Vd), supracommissural part of the ventral telencephalic area (Vs), postcommissural part of the ventral telencephalic area (Vp), preoptic area (POA), and nucleus ventralis tuberis (NVT). These regions are known to be involved in the regulation of sexual behavior (Vd, Vs, Vp, POA) or the HPG axis (NVT). These ER‐ and/or AR‐expressing neurons may regulate sexual behavior or the HPG axis according to their axonal projections. Future analysis should be targeted to the neurons described in the present study to extend our understanding of the central regulatory mechanisms of reproduction. J. Comp. Neurol. 521:1760–1780, 2013. © 2012 Wiley Periodicals, Inc.     

G protein‐coupled receptor 30 contributes to improved remyelination after cuprizone‐induced demyelination

Estrogen exerts neuroprotective and promyelinating actions. The therapeutic effect has been shown in animal models of multiple sclerosis, in which the myelin sheath is specifically destroyed in the central nervous system. However, it remains unproven whether estrogen is directly involved in remyelination via the myelin producing cells, oligodendrocytes, or which estrogen receptors are involved. In this study, we found that the membrane‐associated estrogen receptor, the G protein‐coupled receptor 30 (GPR30), also known as GPER, was expressed in oligodendrocytes in rat spinal cord and corpus callosum. Moreover, GPR30 was expressed throughout oligodendrocyte differentiation and promyelinating stages in primary oligodendrocyte cultures derived from rat spinal cords and brains. To evaluate the role of signaling via GPR30 in promyelination, a specific agonist for GPR30, G1, was administered to a rat model of demyelination induced by cuprizone treatment. Histological examination of the corpus callosum with oligodendrocyte differentiation stage‐specific markers showed that G1 enhanced oligodendrocyte maturation in corpus callosum of cuprizone‐treated animals. It also enhanced oligodendrocyte ensheathment of dorsal root ganglion (DRG) neurons in co‐culture and myelination in cuprizone‐treated animals. This study is the first evidence that GPR30 signaling promotes remyelination by oligodendrocytes after demyelination. GPR30 ligands may provide a novel therapy for the treatment of multiple sclerosis. © 2012 Wiley Periodicals, Inc.     

Prenatal diethylstilbestrol exposure and cancer risk in women

In the Diethylstilbestrol [DES] Combined Cohort Follow-up, the age- and calendar-year specific standardized incidence ratio [SIR] for clear cell adenocarcinoma [CCA] was 27.6 (95% confidence interval [CI] 7.51-70.6) for the exposed women. The SIR for breast cancer was 1.17 (95% CI 1.01-1.36) and the hazard ratio [HR] adjusted for birth year and cohort for comparison with the unexposed was 1.05 (95% CI 0.79-1.41). The SIR for pancreatic cancer was 2.43 (95% CI 1.21-4.34) and the adjusted HR for comparison with unexposed women was 7.16 (95% CI 0.84-61.5). There was little evidence of excess risk for other sites. There appeared to be a deficit in risk for endometrial cancer among the exposed (SIR 0.61; 95% CI 0.35-0.98), and an excess in the unexposed (SIR 1.55; 95% CI 0.95-2.40); the adjusted HR was 0.45 (95% CI 0.22-0.93) for the internal comparison. There was no overall excess cancer risk in exposed women compared with general population rates (1.06; 95% CI 0.95-1.17) or with unexposed participants (adjusted HR 1.03; 95% CI 0.84-1.25). These data do not support the suggestion that there is a diathesis of cancers in DES exposed female offspring The excess risk of breast and pancreatic cancers that we observed is concerning and warrants continued follow-up and mechanistic investigation. Environ. Mol. Mutagen. 60:395–403, 2019. Published 2017. This article is a US Government work and is in the public domain in the USA.     

Differential modulation of activity related to the anticipation of monetary gains and losses across the menstrual cycle

Estradiol and progesterone interact with the dopaminergic and other neurotransmitter systems that are involved in the processing of rewards. On the systems level, these hormones modulate responses to stimulants as well as neuronal activity related to the anticipation of monetary gains. As different mechanisms might underlie the processing of gains and losses, the current study aims to investigate whether neural correlates of gain and loss anticipation are differentially modulated by menstrual cycle phases. Therefore, young, naturally cycling women were examined by means of functional neuroimaging during performing a modified version of the ‘Monetary Incentive Delay’ task in the early follicular and in the luteal menstrual cycle phase. During the low hormone early follicular phase, the anticipation of high vs. low gains and losses was associated with activity in a largely overlapping network of brain areas. However, high hormone levels in the luteal phase affected brain activity in these areas differentially during the anticipation of high vs. low gains and losses. In particular, the orbitofrontal cortex showed a reduced sensitivity to gain magnitude, whereas the ventral striatum and the anterior cingulate showed a reduced sensitivity to loss magnitude. In summary, the high amount of progesterone and estradiol in the luteal phase decreased activity related to the anticipation of monetary gains and losses in different brain areas, suggesting that hormones modulate different processes during the anticipation of gain and loss magnitude.     

雷洛昔酚对大鼠垂体的作用

目的 观察雷洛昔酚是否能诱发出催乳素瘤的动物模型以及对PRL水平的影响,以研究雷洛昔酚对大鼠垂体的作用。方法雌性Wistar大鼠切除卵巢后,分别在皮下埋植含有雷洛昔酚、雌激素和空白硅胶管,术后8周处死大鼠,检测大鼠体重变化、垂体重量变化、血清催乳素(PRL)水平和垂体组织学变化。结果雷洛昔酚组与阴性对照组大鼠体重无明显统计学差异,与雌激素组大鼠体重具有统计学差异(P<0.05)；雷洛昔酚组与阴性对照组大鼠垂体重相比无明显差异,与雌激素组大鼠垂体重相比具有统计学差异(P<0.05)；雌激素组大鼠血清PRL水平最高,阴性对照组血清PRL水平最低,雷洛昔酚组介于两者之间,分别与雌激素组、对照组相比较差异均具有统计学意义(P<0.05)；雷洛昔酚组与对照组垂体病理为正常细胞形态,雌激素组垂体病理为PRL瘤表现。结论雷洛昔酚对大鼠垂体有一定的影响,但不能诱发催乳素瘤。     

Bisphenol S Disrupts Estradiol-Induced Nongenomic Signaling in a Rat Pituitary Cell Line: Effects on Cell Functions

Background: Bisphenol A (BPA) is a well-known endocrine disruptor that imperfectly mimics the effects of physiologic estrogens via membrane-bound estrogen receptors (mERα, mERβ, and GPER/GPR30), thereby initiating nongenomic signaling. Bisphenol S (BPS) is an alternative to BPA in plastic consumer products and thermal paper.Objective: To characterize the nongenomic activities of BPS, we examined signaling pathways it evoked in GH₃/B₆/F₁₀ rat pituitary cells alone and together with the physiologic estrogen estradiol (E₂). Extracellular signal-regulated kinase (ERK)– and c-Jun-N-terminal kinase (JNK)–specific phosphorylations were examined for their correlation to three functional responses: proliferation, caspase activation, and prolactin (PRL) release.Methods: We detected ERK and JNK phosphorylations by fixed-cell immunoassays, identified the predominant mER initiating the signaling with selective inhibitors, estimated cell numbers by crystal violet assays, measured caspase activity by cleavage of fluorescent caspase substrates, and measured PRL release by radioimmunoassay.Results: BPS phosphoactivated ERK within 2.5 min in a nonmonotonic dose-dependent manner (10^–15 to 10^–7 M). When combined with 10^–9 M E₂, the physiologic estrogen’s ERK response was attenuated. BPS could not activate JNK, but it greatly enhanced E₂-induced JNK activity. BPS induced cell proliferation at low concentrations (femtomolar to nanomolar), similar to E_2. Combinations of both estrogens reduced cell numbers below those of the vehicle control and also activated caspases. Earlier activation of caspase 8 versus caspase 9 demonstrated that BPS initiates apoptosis via the extrinsic pathway, consistent with activation via a membrane receptor. BPS also inhibited rapid (≤ 1 min) E₂-induced PRL release.Conclusion: BPS, once considered a safe substitute for BPA, disrupts membrane-initiated E₂-induced cell signaling, leading to altered cell proliferation, cell death, and PRL release.     

Effects of estradiol and progestogens on human breast cells: Regulation of sex steroid receptors

ObjectivesTo examine the effects of 17β-estradiol (E₂) and progestogens, used in hormone therapy, on estrogen receptors (ER), progesterone receptors (PR), and human breast tumor cell growth.Materials and methodsMCF-7 cells were incubated in pure E₂ (1 nM and 10 nM) as well as in E₂ in conjunction with 10 nM progestogens, including progesterone (P4), medroxyprogesterone acetate (MPA), norethisterone acetate (NET), and cyproterone acetate (CPA). Cell proliferation, apoptosis, expression of caspase-3, and both ER and PR isoforms were evaluated.ResultsCaspase-3 was significantly diminished in cultures with only E₂, whereas ERα significantly increased. A significant increase of caspase-3 in addition to the entire abolishment of E₂-induced augmentation of ERα was observed in 1 nM E₂ plus MPA and 10 nM E₂ plus NET, whereas PR isoform B (PRB) was significantly increased. The ratios of apoptosis: proliferation significantly increased in 1 nM E₂ plus progestogens (except P4) and 10 nM E₂ plus NET. The changes of the PRA/PRB ratio were inversely related to the changes of the apoptosis to proliferation ratio. Significant increase of ERβ and PRB was noted in the E₂ plus MPA or NET, in addition to a significant increase of ERα and decrease of PRA in the E₂ plus CPA, as well as an increase of ERα and decrease of PRA and PRB in the E₂ plus P4.ConclusionsThe combination of E₂ and various progestogens resulted in diverging effects on ERs and PRs expressions, which induced different effects on MCF-7 cell growth. Compared with P4, aberrant hormone and biological activity of synthetic progestin, by way of altered receptor expression, may be an important factor in affecting breast cell growth.     

Interpretation of Steroid Receptors in Breast Cancer. A Case With Discordant Estrogen Receptor Results Using ER1D5 and H222 Antibodies

Abstract

We report a case of an invasive duct breast cancer, grade 1 by Bloom and Richardson criteria, and metastatic to axillary nodes and perinodal soft tissue. Immunostaining for estrogen receptor (ER) with ERlD5 resulted in intense positive tumor cell staining with both frozen and paraffin sections. Matching studies using a different anti-estrogen receptor reagent (H222), uniformly produced negative results in 3 different assay systems (EIA-ER, ER-ICA, ER-PAR). This case reveals a discrepancy between reactivity of ERlD5 and H222 that may indicate the presence of outlaw ER variants. It also illustrates the interpretation problems that can arise with new antibodies that have not been fully validated, particularly if the results are used in therapeutic decision making. (The J Histotechnol 18:331, 1995)