http://www.cnr.it/ontology/cnr/individuo/prodotto/ID27500

Alterations in the expression, structure and function of Progesterone Receptor Membrane Component-1 (PGRMC1) in premature ovarian failure. (Articolo in rivista)

Type

Label

Alterations in the expression, structure and function of Progesterone Receptor Membrane Component-1 (PGRMC1) in premature ovarian failure. (Articolo in rivista) (literal)

Anno

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi

Alternative label

Mansouri MR; Schuster J; Badhai J; Stattin EL; Losel R; Wehling M; Carlsson B; Hovatta O; Karlstrom PO; Golovleva I; Toniolo D; Bione S; Peluso J; Dahl N. (2008)
Alterations in the expression, structure and function of Progesterone Receptor Membrane Component-1 (PGRMC1) in premature ovarian failure.
in Human molecular genetics (Print); Oxford University Press, Oxford (Regno Unito)
(literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

Mansouri MR; Schuster J; Badhai J; Stattin EL; Losel R; Wehling M; Carlsson B; Hovatta O; Karlstrom PO; Golovleva I; Toniolo D; Bione S; Peluso J; Dahl N. (literal)

Pagina inizio

Pagina fine

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#url

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

Rivista

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#pagineTotali

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo

Note

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden; Medical and Clinical Genetics, Department of Medical Biosciences, Umeå University, Umeå, Sweden; Clinical Pharmacology Mannheim, University of Heidelberg, Mannheim, Germany; Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden; Department of Women's and Children's Health, Academic Hospital, Uppsala, Sweden; Institute of Molecular Genetics, Consiglio Nazionale delle Ricerche (CNR), Pavia, Italy; Department of Biotechnologial Research (DIBIT), San Raffaele Scientific Institute, Milano, Italy; Department of Cell Biology, University of CT Health Center, Farmington, CT, USA. (literal)

Titolo

Alterations in the expression, structure and function of Progesterone Receptor Membrane Component-1 (PGRMC1) in premature ovarian failure. (literal)

Abstract

Premature ovarian failure (POF) is characterized by hypergonadotropic hypogonadism and amenorrhea before the age of 40. The condition has a heterogeneous background but genetic factors are demonstrated by the occurrence of familial cases. We identified a mother and daughter with POF both of whom carry an X;autosome translocation [t(X;11)(q24;q13)]. RNA expression studies of genes flanking the X-chromosome breakpoint revealed that both patients have reduced expression levels of the gene Progesterone Receptor Membrane Component-1 (PGRMC1). Mutation screening of 67 females with idiopathic POF identified a third patient with a missense mutation (H165R) located in the cytochrome b5 domain of PGRMC1. PGRMC1 mediates the anti-apoptotic action of progesterone in ovarian cells and it acts as a positive regulator of several cytochrome P450 (CYP)-catalyzed reactions. The CYPs are critical for intracellular sterol metabolism, including biosynthesis of steroid hormones. We show that the H165R mutation associated with POF abolishes the binding of cytochrome P450 7A1 (CYP7A1) to PGRMC1. In addition, the missense mutation attenuates PGRMC1's ability to mediate the anti-apoptotic action of progesterone in ovarian cells. These findings suggest that mutant or reduced levels of PGMRC1 may cause POF through impaired activation of the microsomal cytochrome P450 and increased apoptosis of ovarian cells. (literal)

Editore