Immature ovaries and polycystic kidneys in the congenital polycystic kidney mouse may be due to abnormal sex steroid metabolism

Mol Cell Endocrinol. 2001 May 15;176(1-2):155-62. doi: 10.1016/s0303-7207(00)00398-1.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 17-Hydroxysteroid Dehydrogenases / metabolism
  • Animals
  • Chorionic Gonadotropin / pharmacology
  • Dihydrotestosterone / metabolism
  • Disease Models, Animal*
  • Estradiol / metabolism
  • Estrone / metabolism
  • Fallopian Tubes / metabolism
  • Female
  • Histocompatibility Antigens / metabolism
  • Homozygote
  • Immunohistochemistry
  • Kidney / enzymology
  • Kidney / metabolism
  • Liver / enzymology
  • Liver / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Mutation / genetics
  • Ovary / drug effects
  • Ovary / enzymology
  • Ovary / metabolism*
  • Ovary / pathology*
  • Oxidoreductases*
  • Polycystic Kidney, Autosomal Recessive / enzymology
  • Polycystic Kidney, Autosomal Recessive / genetics
  • Polycystic Kidney, Autosomal Recessive / metabolism*
  • Polycystic Kidney, Autosomal Recessive / pathology*
  • Rats
  • Steroids / metabolism*
  • Superovulation / drug effects
  • Testosterone / metabolism

Substances

  • Chorionic Gonadotropin
  • H2-Ke6 protein, mouse
  • Histocompatibility Antigens
  • Steroids
  • Dihydrotestosterone
  • Estrone
  • Testosterone
  • Estradiol
  • Oxidoreductases
  • 17-Hydroxysteroid Dehydrogenases
  • 3 (or 17)-beta-hydroxysteroid dehydrogenase