Postnatal exposure to androgens alters renal ornithine decarboxylase ontogeny and abolishes renal sexual dimorphism in mice.
The mouse kidney presents marked sexual dimorphism, manifested not only in renal size but also in the subcellular structure and enzyme activity. Ornithine decarboxylase (ODC), a key enzyme in the biosynthetic pathway of polyamines, is induced in the kidney by androgens, and its activity is higher in the kidney of male mice. The renal differences between male and female mice are not manifested during the first weeks of life and start to be expressed after weaning, simultaneously with the increase in plasma testosterone concentration. Treatment of newborn mice before postnatal day 21 with a single dose of testosterone propionate (TP, 200 microg/animal) did not increase renal ODC activity or renal size. From day 21 the same treatment elicited significant increases in renal ODC, especially in females where the basal activity of control animals was much lower than in males. The repeated injection of TP during the first 10 days of life (200 microg/animal, days 1, 4, 7 and 10) promoted an early increase in renal ODC activity but abolished the physiological rise observed in male mice at puberty and adulthood. This treatment dramatically reduced the secretion of the sexual hormones, testosterone, estradiol and progesterone, by the gonads, and diminished renal size as well as ODC and beta-glucuronidase activities in male mice. Stanozolol produced effects similar to those of TP, while the nonsteroidal antiandrogen, flutamide, did not apparently affect the normal development of the male or female kidney. The results indicate that: (a) kidney sexual dimorphism is not congenital; (b) neonatal androgens are not required to induce the sexual dimorphism of the mouse kidney; (c) the neonatal kidney is unresponsive to testosterone; (d) the premature and repeated exposure to supraphysiological levels of testosterone may accelerate the ontogeny of renal ODC but can abolish later testosterone secretion and hence alter the sexual characteristics of the male kidney, and (e) the postnatal treatment with androgens does not affect the response of the adult kidney to exogenous androgens. One can conclude that the postnatal manipulation of androgens may accelerate the development of the mechanisms of androgen responsiveness in some tissues but it may alter neural structures, probably the GnRH pulse generator, that control testosterone secretion.
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Murcia, Spain.
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Sánchez-Capelo
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Tejada
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Ruzafa
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Cremades
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Peñafiel
D000375:Aging; D000818:Animals; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005966:Glucuronidase / Q000378:metabolism / Q000652:urine; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development*; D007700:Kinetics; D008297:Male; D051379:Mice; D009955:Ornithine Decarboxylase / Q000096:biosynthesis / Q000378:metabolism*; D011700:Putrescine / Q000652:urine; D012727:Sex Characteristics; D012741:Sexual Maturation; D013739:Testosterone / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*
D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D005966:Glucuronidase; D009955:Ornithine Decarboxylase; D011700:Putrescine