Immature ovaries and polycystic kidneys in the congenital polycystic kidney mouse may be due to abnormal sex steroid metabolism.
Ke 6 is a 17beta-hydroxysteroid dehydrogenase (17betaHSD) that is expressed in the kidneys and gonads. The expression of this gene is markedly reduced in three murine models of recessive polycystic kidney disease, a developmental disorder, where some nephrons within the affected kidneys develop into huge fluid-filled cysts while the non-cystic nephrons atrophies by apoptosis. Here, we show that in the cpk/cpk mouse, which have polycystic kidneys, the female reproductive organs also fail to mature properly and remain arrested at an early stage of development. Direct measurement of 17betaHSD activity showed a severe reduction in estrogen and androgen metabolism within gonadal and non-gonadal tissues of the cpk/cpk mouse. Using immunofluorescent staining we localized the expression of the Ke 6 protein within the female mouse reproductive organs. Our findings suggest that estrogen/androgen metabolism may play an important role in the development of the urogenital systems.
Woo
D
D
Department of Medicine, University of California, Los Angeles, CA 90095, USA.
Lee
G Y
GY
Anderson
E
E
Aziz
N
N
D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000378:metabolism; D004195:Disease Models, Animal; D004958:Estradiol / Q000378:metabolism; D004970:Estrone / Q000378:metabolism; D005187:Fallopian Tubes / Q000378:metabolism; D005260:Female; D006649:Histocompatibility Antigens / Q000378:metabolism; D006720:Homozygote; D007150:Immunohistochemistry; D007668:Kidney / Q000201:enzymology / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009154:Mutation / Q000235:genetics; D010053:Ovary / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D010088:Oxidoreductases; D017044:Polycystic Kidney, Autosomal Recessive / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D013256:Steroids / Q000378:metabolism*; D013480:Superovulation / Q000187:drug effects; D013739:Testosterone / Q000378:metabolism
D006063:Chorionic Gonadotropin; C079876:H2-Ke6 protein, mouse; D006649:Histocompatibility Antigens; D013256:Steroids; D013196:Dihydrotestosterone; D004970:Estrone; D013739:Testosterone; D004958:Estradiol; D010088:Oxidoreductases; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase