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The prostate gland develops from the urogenital sinus as epithelial buds projecting into the surrounding mesenchyme. The role of the mesenchyme in this process was determined using sinuses from normal and androgen-insensitive Tfm mice which are deficient in androgen receptors. Epithelium and mesenchyme from both types of sinus were separated and recombined and the recombinants grown in organ culture in the presence of testosterone. Recombinants consisting of normal epithelium and normal mesenchyme developed epithelial buds projecting into the surrounding mesenchyme but no buds were formed in recombinants of epithelium and mesenchyme from mutant mice. In recombinants of epithelium from mutant mice with normal mesenchyme the epithelium developed prostatic buds and the number was similar to that found if normal epithelium was associated with normal mesenchyme. In contrast, normal epithelium combined with mesenchyme from mutant mice failed to form prostatic buds. The results suggested that the mesenchyme determines the development of prostatic buds and that the lack of inductive capacity of the mesenchyme from mutant mice may be due to a deficiency of mesenchymal androgen receptors.

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The androgen dependency of prostatic bud formation in fetal rat urogenital sinuses was studied using brief treatments with androgen, and the incorporation of androgens by the sinus mesenchyme was followed by steroid autoradiography. Urogenital sinuses from 16.5-day fetuses of both sexes were grown in organ culture and treated with androgens for periods ranging from 4 to 72 h and then transferred to control medium. A minimum treatment of 24 h was required to induce prostatic buds in male sinuses and of 36 h in all female sinuses. This difference in response disappeared after more prolonged treatment. In both sexes the number of prostatic buds increased with the time of exposure to androgens. Prostatic bud formation continued for 24-36 h after transfer to control medium. Steroid autoradiographic analysis showed that the labelled androgen was concentrated in the mesenchymal nuclei. The rate of incorporation rose steeply during the first 12 h and then more slowly. After transfer to control medium the amount of labelled androgen decreased rapidly to half within 12 h and then decreased more slowly. In the competition experiments a 200-fold excess of unlabelled testosterone or dihydrotestosterone in the labelling medium greatly reduced the nuclear labelling with [3H]testosterone.

Rat prostate glands are induced de novo by androgens in 16\m=.\5-day-old male and female urogenital sinuses in vitro as epithelial buds projecting into the surrounding mesenchyme. The role of the mesenchyme in this process has been investigated in various epi thel i al \x=req-\ mesenchymal recombinations in organ culture.Isolated epithelium did not form buds but required the presence of the mesenchyme to do so. This requirement seemed to be specific; in the presence of testosterone or dihydrotestosterone only urogenital mesenchyme increased cell division in the urogenital epithelium and stimulated prostatic bud formation. In contrast, heterotypic mesenchyme did not affect epithelial mitosis and failed to induce buds while heterotypic epithelia did not respond to urogenital mesenchyme.In recombinants of urogenital mesenchyme pretreated with androgen and untreated urogenital epithelium, grown in androgen-free medium, the majority of explants developed prostatic buds while only a few buds were formed from epithelium pretreated with androgen when it was recombined with untreated mesenchyme.The role of the mesenchyme in the loss of androgen responsiveness of the older female sinuses was examined in heterochronic recombinants. It was found that the old female mesenchyme failed to induce buds in young epithelium while young male or female mesenchymes induced them in the old female epithelium. The results suggest that the urogenital mesenchyme is essential for the initiation of the foetal rat prostate gland and that it may be a target for androgens and complement or mediate their effect on the epithelium.