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Perinatal sex-steroid exposure may result in permanent modifications in the structure and function of the prostate gland. The mechanism of such long-range alterations in hormonal sensitivity is not known. This study aimed to define the molecular requirements for neonatal sex-steroid imprinting and to investigate whether combined administration of neonatal androgens and estrogens had synergistic effects upon the mature mouse prostate. Since the interaction between endogenous and exogenous sex steroids in normal mice makes it difficult to dissociate direct from indirect effects, we used the hypogonadal (hpg) mouse, characterized by congenital androgen deficiency yet still fully responsive to exogenous androgens. Newborn mice (Days 1-2) were administered a single s.c. injection of androgens alone or in combination with an estrogen followed by testosterone-induced maximal prostate growth at maturity. The final effects were determined in 7-wk-old mice through study of ductal architecture in microdissected ventral prostates (VP) and quantitation of volume densities and diameters of prostate tissue components. A single neonatal dose of androgens, but not of estrogen, increased branching morphogenesis and VP weights at adulthood. These effects did not differ significantly between various androgens; in addition, combined androgen and estrogen treatment failed to demonstrate any synergistic effects on the prostate. We conclude that neonatal androgens induce long-range effects upon the mature VP structure as well as its secretory function and that this imprinting occurs via the androgen receptor without requiring aromatization of androgens. However, these conclusions, based on a specific treatment protocol, are confined only to the distal segment of VP, and effects of neonatal sex-steroid exposure in other regions or lobes of VP may differ.

Imprinting by Neonatal Sex Steroids on the Structure and Function of the Mature Mouse Prostate1