Deletion of steroid 5α-reductase 2 gene in male pseudohermaphroditism
TLDR
The results verify the existence of at least two 5α-reductases in man and provide insight into a fundamental hormone-mediated event in male sexual differentiation.Abstract:
THE conversion of testosterone into dihydrotestosterone by steroid 5α-reductase is a key reaction in androgen action, and is essential both for the formation of the male phenotype during embryogenesis and for androgen-mediated growth of tissues such as the prostate1,2. Single gene defects that impair this conversion lead to pseudohermaphroditism in which 46 X, Y males have male internal urogenital tracts, but female external genitalia3. We have described the isolation of a human 5α-reductase complementary DNA from prostate4. Subsequent cloning and genetic studies showed that this gene (designated 5α-reductase 1) was normal in patients with Sor-reductase deficiency26. We report here the isolation of a second 5α-reductase cDNA by expression cloning and the polymerase chain reaction. The biochemical and pharmacological properties of this cDNA-encoded enzyme (designated 5α-reductase 2) are consistent with it being the major isozyme in genital tissue. A deletion in this gene is present in two related individuals with male pseudohermaphroditism caused by 5α-reductase deficiency. These results verify the existence of at least two 5α-reductases in man and provide insight into a fundamental hormone-mediated event in male sexual differentiation.read more
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The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders.
TL;DR: Understanding steroidogenesis is of fundamental importance to understanding disorders of sexual differentiation, reproduction, fertility, hypertension, obesity, and physiological homeostasis.
Journal ArticleDOI
Neurosteroids: Biosynthesis and Function of These Novel Neuromodulators
TL;DR: This paper summarizes what is known about the biosynthesis of neurosteroids, the enzymes mediating these reactions, their localization during development and in the adult, and their function and mechanisms of action in the developing and adult central and peripheral nervous systems.
Journal ArticleDOI
Weight gain decreases elevated plasma ghrelin concentrations of patients with anorexia nervosa
Bärbel Otto,U Cuntz,E Fruehauf,R. Wawarta,Christian Folwaczny,Rudolf L. Riepl,Mark L. Heiman,P. Lehnert,Manfred M. Fichter,Matthias H. Tschöp +9 more
TL;DR: Fasting plasma levels of the novel appetite-modulating hormone ghrelin are elevated in anorexia nervosa and return to normal levels after partial weight recovery, suggesting the possible existence of ghrel in resistance in cachectic states such as caused by eating disorders.
Journal ArticleDOI
Tissue distribution and ontogeny of steroid 5 alpha-reductase isozyme expression.
Anice E. Thigpen,Richard I. Silver,Joseph M. Guileyardo,M L Casey,John D. McConnell,David W. Russell +5 more
TL;DR: Results are consistent with 5 alpha-reductase type 1 being responsible for virilization in type 2-deficient subjects during puberty, and suggest that the type 2 isozyme may be an initiating factor in development of male pattern baldness.
Journal ArticleDOI
Spastin, a new AAA protein, is altered in the most frequent form of autosomal dominant spastic paraplegia
Jamilé Hazan,Nuria Fonknechten,Delphine Mavel,Caroline Paternotte,Delphine Samson,François Artiguenave,Claire-Sophie Davoine,Corinne Cruaud,Alexandra Durr,Patrick Wincker,Philippe Brottier,Laurence Cattolico,Valérie Barbe,Jean-Marc Burgunder,Jean-François Prud'homme,Alexis Brice,Bertrand Fontaine,Roland Heilig,Jean Weissenbach +18 more
TL;DR: The sequence homologies and putative subcellular localization of spastin suggest that this ATPase is involved in the assembly or function of nuclear protein complexes.
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