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. Ornit hine decarboxylase (ODC), a key enzyme in the biosynthetic pathway of polya mines, 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 mic e are not manifested during the first weeks of life and start to be express ed after weaning, simultaneously with the increase in plasma testosterone c oncentration. Treatment of newborn mice before postnatal day 21 with a sing le dose of testosterone propionate (TP, 200 mu g/animal) did not increase r enal ODC activity or renal size. From day 21 the same treatment elicited si gnificant increases in renal ODC, especially in females where the basal act ivity of control animals was much lower than in males. The repeated injecti on of TP during the fi rst 10 days of life (200 mu g/animal, days 1, 4, 7 a nd 10) promoted an early increase in renal ODC activity but abolished the p hysiological rise observed in male mice at puberty and adulthood. This trea tment dramatically reduced the secretion of the sexual hormones, testostero ne, estradiol and progesterone, by the gonads, and diminished renal size as well as ODC and P-glucuronidase activities in male mice. Stanozolol produc ed effects similar to those of TP, while the nonsteroidal antiandrogen, flu tamide, did not apparently affect the normal development of the male or fem ale kidney. The results indicate that: (a) kidney sexual dimorphism is not congenital; (b) neonatal androgens are not required to induce the sexual di morphism of the mouse kidney; (c) the neonatal kidney is unresponsive to te stosterone; (d) the premature and repeated exposure to supraphysiological l evels of testosterone may accelerate the ontogeny of renal ODC but can abol ish later testosterone secretion and hence alter the sexual characteristics of the male kidney, and (e) the postnatal treatment with androgens does no t affect the response of the adult kidney to exogenous androgens. One can c onclude that the postnatal manipulation of androgens may accelerate the dev elopment of the mechanisms of androgen responsiveness in some tissues but i t may alter neural structures, probably the GnRH pulse generator, that cont rol testosterone secretion.