Alpha-fetoprotein controls female fertility and prenatal development of the gonadotropin-releasing hormone pathway through an antiestrogenic action

It has been shown previously that female mice homozygous for an alpha-fetoprotein (AFP) null allele are sterile as a result of anovulation, probably due to a defect in the hypothalamic-pituitary axis. Here we show that these female mice exhibit specific anomalies in the expression of numerous genes in the pituitary, including genes involved in the gonadotropin-releasing hormone pathway, which are underexpressed. In the hypothalamus, the gonadotropin-releasing hormone gene, Gnrh1, was also found to be down-regulated. However, pituitary gene expression could be normalized and fertility could be rescued by blocking prenatal estrogen synthesis using an aromatase inhibitor. These results show that AFP protects the developing female brain from the adverse effects of prenatal estrogen exposure and clarify a long-running debate on the role of this fetal protein in brain sexual differentiation.

Assessing segmentation processes by click detection: online measure of statistical learning, or simple interference?

Statistical learning can be used to extract the words from continuous speech. Gómez, Bion, and Mehler (Language and Cognitive Processes, 26, 212–223, 2011) proposed an online measure of statistical learning: They superimposed auditory clicks on a continuous artificial speech stream made up of a random succession of trisyllabic nonwords. Participants were instructed to detect these clicks, which could be located either within or between words. The results showed that, over the length of exposure, reaction times (RTs) increased more for within-word than for between-word clicks. This result has been accounted for by means of statistical learning of the between-word boundaries. However, even though statistical learning occurs without an intention to learn, it nevertheless requires attentional resources. Therefore, this process could be affected by a concurrent task such as click detection. In the present study, we evaluated the extent to which the click detection task indeed reflects successful statistical learning. Our results suggest that the emergence of RT differences between within- and between-word click detection is neither systematic nor related to the successful segmentation of the artificial language. Therefore, instead of being an online measure of learning, the click detection task seems to interfere with the extraction of statistical regularities.

Espaces d’interdépendance entre action publique et experts: Etat réflexif dans le champ du sida

info:eu-repo/semantics/published

Characteristics of the biphasic action of androgens and of the potent antiproliferative effects of the new pure antiestrogen EM-139 on cell cycle kinetic parameters in LNCaP human prostatic cancer cells

The most potent steroid in human prostatic carcinoma LNCaP cells, i.e. dihydrotestosterone (DHT), has a biphasic stimulatory effect on cell proliferation. At the maximal stimulatory concentration of 0.1 nM DHT, analysis of cell kinetic parameters shows a decrease of the G0-G1 fraction with a corresponding increase of the S and G2 + M fractions. In contrast, concentrations of 1 nM DHT or higher induce a return of cell proliferation to control levels, reflected by an increase in the G0-G1 fraction at the expense of the S and especially the G2 + M fractions. Continuous labeling for 144 h with the nucleotide analogue 5'-bromodeoxyuridine shows that the percentage of cycling LNCaP cells rises more than 90% after treatment with stimulatory concentrations of DHT, whereas in control cells as well as in cells treated with high concentrations of the androgen, this value remains below 50%. Although LNCaP cells do not contain detectable estrogen receptors, the new pure steroidal antiestrogen EM-139 not only reversed the stimulation of cell proliferation and cell kinetics induced by stimulatory doses of DHT but also inhibited basal cell proliferation.