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.

Alpha-fetoprotein protects the developing female mouse brain from masculinization and defeminization by estrogens

Two clearly opposing views exist on the function of alpha-fetoprotein (AFP), a fetal plasma protein that binds estrogens with high affinity, in the sexual differentiation of the rodent brain. AFP has been proposed to either prevent the entry of estrogens or to actively transport estrogens into the developing female brain. The availability of Afp mutant mice (Afp-/-) now finally allows us to resolve this longstanding controversy concerning the role of AFP in brain sexual differentiation, and thus to determine whether prenatal estrogens contribute to the development of the female brain. Here we show that the brain and behavior of female Afp-/- mice were masculinized and defeminized. However, when estrogen production was blocked by embryonic treatment with the aromatase inhibitor 1,4,6-androstatriene-3,17- dione, the feminine phenotype of these mice was rescued. These results clearly demonstrate that prenatal estrogens masculinize and defeminize the brain and that AFP protects the female brain from these effects of estrogens. © 2006 Nature Publishing Group.

Health networks: Actors, professional relationships, and controversies

In recent years international policies have aimed to stimulate the use of information and communication technologies (ICT) in the field of health care. Belgium has also been affected by these developments and, for example, health electronic regional networks ("HNs") are established. Thanks to a qualitative case study we have explored the implementation of such innovations (HN) to better understand how health professionals collaborate through the HN and how the HN affect their relationships. Within the HNs studied a common good unites the actors: the continuity of care for a better quality of care. However behind this objective of continuity of care other individual motivations emerge. Some controversies need also to be resolved in order to achieve cooperative relationships. HNs have notably to take national developments into account. These developments raise the question of the control of medical knowledge and medical practice. Professional issues, and not only practical changes, are involved in these innovations. © 2008 The authors and IOS Press. All rights reserved.