Environmental Exposure to Polychlorinated Biphenyls and p,p´-DDE and Sperm Sex-Chromosome Disomy

Background: Chromosomal abnormalities contribute substantially to reproductive problems, but the role of environmental risk factors has received little attention

Requirement of estrogen receptor-alpha in insulin-like growth factor-1 (IGF-1)-induced uterine responses and in vivo evidence for IGF-1/estrogen receptor cross-talk

In the uterus insulin-like growth factor-1 (IGF-1) signaling can be initiated by estradiol acting through its nuclear receptor (estrogen receptor (ER)) to stimulate the local synthesis of IGF-1. Conversely, in vitro studies have demonstrated that estradiol-independent ER transcriptional activity can be induced by IGF-1 signaling, providing evidence for a cross-talk mechanism between IGF-1 and ER. To investigate whether ERalpha is required for uterine responses to IGF-1 in vivo, both wild-type (WT) and ERalpha knockout (alphaERKO) mice were administered IGF-1, and various uterine responses to IGF-1 were compared. In both WT and alphaERKO mice, IGF-1 treatment resulted in phosphorylation of uterine IGF-1 receptor (IGF-1R) and formation of an IGF-1R/insulin receptor substrate-1/ phosphatidylinositol 3-kinase signaling complex. In addition, IGF-1 stimulated phosphorylation of uterine Akt and MAPK in both WT and alphaERKO mice. However, IGF-1 treatment stimulated BrdUrd incorporation and proliferating cell nuclear antigen expression in WT uteri only. To determine whether ERalpha can be activated in vivo by IGF-1 signaling, transgenic mice carrying a luciferase gene driven by two estrogen response elements (ERE-luciferase mice) were utilized. Treatment of ovariectomized ERE-luciferase mice with IGF-1 resulted in an increase in uterine luciferase activity that was attenuated in the presence of the ER antagonist ICI 182,780. Together these data demonstrate that 1) functional signaling proximal to IGF-1R is maintained in the alphaERKO mouse uterus, 2) ERalpha is necessary for IGF-1 induction of uterine nuclear proliferative responses, and 3) cross-talk between IGF-1R and ER signaling pathways exists in vivo

Genetic contributions to generalized arousal of brain and behavior

We have identified a generalized arousal component in the behavior of mice. Analyzed by mathematical/statistical approaches across experiments, investigators, and mouse populations, it accounts for about 1/3 of the variance in arousal-related measures. Knockout of the gene coding for the classical estrogen receptor (ER-α), a ligand-activated transcription factor, greatly reduced arousal responses. In contrast, disrupting the gene for a likely gene duplication product, ER-β, did not have these effects. A combination of mathematical and genetic approaches to arousal in an experimentally tractable mammal opens up analysis of a CNS function of considerable theoretical and practical significance

Estrogen inhibits the vascular injury response in estrogen receptor beta -deficient female mice

The protective effects of estrogen in the cardiovascular system result from both systemic effects and direct actions of the hormone on the vasculature. Two estrogen receptors have been identified, ERα and ERβ. We demonstrated previously that estrogen inhibits the response to vascular injury in both wild-type and ERα-deficient mice, and that ERβ is expressed in the blood vessels of each, suggesting a role for ERβ in the vascular protective effects of estrogen. In the present study, we examined the effect of estrogen administration on mouse carotid arterial injury in ERβ-deficient mice. Surprisingly, in ovariectomized female wild-type and ERβ knockout mice, 17β-estradiol markedly and equally inhibited the increase in vascular medial area and the proliferation of vascular smooth muscle cells after vascular injury. These data demonstrate that ERβ is not required for estrogen-mediated inhibition of the response to vascular injury, and suggest that either of the two known estrogen receptors is sufficient to protect against vascular injury, or that another unidentified estrogen receptor mediates the vascular protective effects of estrogen

Patients with type A acute aortic dissection presenting with major brain injury: Should we operate on them?

none20siopenDi Eusanio, Marco*; Patel, Himanshu J.; Nienaber, Christoph A.; Montgomery, Daniel M.; Korach, Amit; Sundt, Thoralf M.; Devincentiis, Carlo; Voehringer, Matthias; Peterson, Mark D.; Myrmel, Truls; Folesani, Gianluca; Larsen, Magnus; Desai, Nimesh D.; Bavaria, Joseph E.; Appoo, Jehangir J.; Kieser, Teresa M.; Fattori, Rossella; Eagle, Kim; Di Bartolomeo, Roberto; Trimarchi, SantiDi Eusanio, Marco; Patel, Himanshu J.; Nienaber, Christoph A.; Montgomery, Daniel M.; Korach, Amit; Sundt, Thoralf M.; Devincentiis, Carlo; Voehringer, Matthias; Peterson, Mark D.; Myrmel, Truls; Folesani, Gianluca; Larsen, Magnus; Desai, Nimesh D.; Bavaria, Joseph E.; Appoo, Jehangir J.; Kieser, Teresa M.; Fattori, Rossella; Eagle, Kim; Di Bartolomeo, Roberto; Trimarchi, Sant

Estrogen regulation of mammary gland development and breast cancer: amphiregulin takes center stage

Estrogen-mediated proliferation is fundamental to normal mammary gland development. Recent studies have demonstrated that amphiregulin is a critical paracrine regulator of estrogen action during ductal morphogenesis. These studies implicate a critical role for amphiregulin in mammary stem cell differentiation as well as breast cancer initiation and progression