Objectif
The differentiation of male and female phenotype is established at 7-12 weeks post conceptionem. During this period, maintaining the appropiate intrauterine hormone environment is essential. In contrast to other species, the regulation of human sexual differentiation is linked with the development of the adrenal cortex, as can be concluded from the disorders (virilization and adrenal insufficiency in the newborn) observed in patients suffering from congenital adrenal hyperplasia (CAH), one of the most common known autosomal recessive disorders. Until now, the explanation for the corrupted sexual differentiation in CAH is mainly hypothetical and relies heavily upon extrapolation from the adult adrenocortical function. The so far widely accepted explanation upon regulation of steroidogenesis during development is based on the description of the so called classical pathway of steroidogenesis. In this pathway the conversion of 17-hydroxyprogesterone to dehydroepiandrosterone (DHEA) plays a pivotal role. Recent data of the host lab, however, indicate the existance of an alternative, previously unrecognized pathway in human androgen synthesis present in fetal and early neonatal life only, not involving DHEA. As the structure and function of the human fetal adrenal gland is unique and different from the adult human adrenal gland and rodents do not synthesize adrenal androgens at all, the studies require the analysis of human fetal tissue.The main goal of this project is to determine the expression and activity of the proposed alternative androgen pathway during normal human fetal development and its significance for sexual differentiation and disordered sex development. The proposed alternative androgen pathway may play a crucial role in the prenatal virilization of females suffering from CAH due to 21-hydroxylase deficiency and it is very likely that it plays an important role in normal human sexual differentiation and maintenace of pregnancy.
Champ scientifique
Mots‑clés
Thème(s)
Appel à propositions
FP7-PEOPLE-2007-2-1-IEF
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Régime de financement
MC-IEF - Intra-European Fellowships (IEF)Coordinateur
B15 2TT Birmingham
Royaume-Uni