title: Comparative assessment of estrogenic responses with relevance to the metabolic syndrome and to menopausal symptoms in wild-type and aromatase-knockout mice.
abstract: Knockout of the Cyp-19 gene (aromatase) renders mice to have insufficient endogenous estrogen production and contributes to the development of symptoms related the metabolic syndrome, including excess adiposity and insulin resistance. This study comparatively assessed the estrogen responsiveness in animal models of genetical versus surgical (ovariectomy) origin of estrogen deficiency. Evaluation of physiological parameters and gene expression pattern in response to estrogens revealed differences in estrogen responsiveness between aromatase deficient and castrated or intact wild-type mice. ArKO mice had a significantly higher bodyweight than matched ovariectomized wild-type mice. The weight of the completely regressed uterus following ovariectomy was higher than the uterine weight of ArKO mice. Further, alterations in metabolic parameters like increased serum leptin levels and decreased plasma glucose levels in genetically deficient mice became apparent. Finally, expression pattern of estrogen responsive genes differed in the two experimental models of estrogen deficiency. Both, in uterine and adipose tissues the regulation of expression of some genes either was inversed of regulation or considerably differed in the magnitude of the response in the two models. Our studies demonstrate that the cause of estrogen deficiency significantly impacts on estrogen responsiveness and may be of relevance for investigations on aspects of estrogen deficiency and metabolic and/or menopausal symptoms.
authors.affiliation: Institute of Zoology, Technische Universität Dresden, 01062 Dresden, Germany. manuela.bader@tu-dresden.de
authors.forename: Manuela I
authors.initials: MI
authors.lastname: Bader
authors.forename: Jannette
authors.initials: J
authors.lastname: Wober
authors.forename: Georg
authors.initials: G
authors.lastname: Kretzschmar
authors.forename: Oliver
authors.initials: O
authors.lastname: Zierau
authors.forename: Günter
authors.initials: G
authors.lastname: Vollmer
mesh_terms: D000818:Animals; D001141:Aromatase / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D017931:DNA Primers; D004967:Estrogens / Q000502:physiology*; D005260:Female; D020869:Gene Expression Profiling; D020738:Leptin / Q000097:blood; D008593:Menopause; D024821:Metabolic Syndrome / Q000503:physiopathology*; D051379:Mice; D018345:Mice, Knockout; D009929:Organ Size; D010052:Ovariectomy; D060888:Real-Time Polymerase Chain Reaction; D014599:Uterus / Q000378:metabolism / Q000473:pathology
chemical_list: D001786:Blood Glucose; D017931:DNA Primers; D004967:Estrogens; D020738:Leptin; D001141:Aromatase