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Gene Activity during the Early Phase of Androgen-stimulated Rat Prostate Regrowth¹

Department of Urology, Maimonides Medical Center, Brooklyn, New York 11219 [A. E. K., G. J. W.], and Department of Urology, Columbia University, New York, New York 10032 [M. C. B., C. A. O., M. G. B., I. S. S., P. T., R. B.]

Androgenic steroids regulate the proliferation rate of normal and malignant prostate cells. In order to investigate the molecular basis of this control, we utilized Northern and Western blot techniques to measure changes in the expression of individual genes during the early phase of prostate regrowth. Vestigial ventral prostate glands of 7-day castrated rats showed increased numbers of replicating cells within 12 h of continuous pharmacological testosterone replacement as demonstrated by flow cytometric procedures. The period prior to the onset of proliferative enhancement was accompanied by the sequential induction of a variety of transcripts encoding gene products often associated with cell growth. Within 1 h of treatment, mature mRNA transcripts for c-fos were induced 6-fold, returning to control levels by 2 h. Other genes showed transiently elevated transcript levels after 2 h (c-Ha-ras, c-Ki-ras) or after 8 h (c-myc, c-myb, ß-actin, and M_r 70,000 heat shock protein) of testosterone replacement. Expression of the polypeptide encoded by c-Ha-ras was coordinately enhanced (2-fold) during this period, but not to the levels of the transcript (20-fold induction). Transcripts encoding basic fibroblast growth factor were increased 16 h and later, subsequent to the earlier enhancement in the proliferation rate. By placing these genes in a defined temporal order with regard to their expression in response to testosterone, we have constructed a map of gene activity during early prostate regrowth. This map shows a number of genes, the products of which might participate in the mechanism by which androgens induce mitogenesis of prostate cells.

¹ This work was partially supported by a grant from the Maimonides Research and Development Foundation and from the NIH (CA47848) (R. B.).

Received 4/ 3/89. Revised 7/21/89. Accepted 8/ 4/89.

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