Alterations of Physical and Biochemical Parameters of the R3327-CP Rat Prostate Adenocarcinoma Following Hormonal Manipulation of the Host

Abstract

Several physical and biochemical parameters of a rapidly growing, hormonally responsive, poorly differentiated strain of Dunning R3327 rat prostatic adenocarcinoma (the CP strain) were monitored for 1 month during growth in control and hormonally manipulated male Fischer X Copenhagen rats. The tumor was implanted into control rats and into rats 1 month following orchiectomy. Twenty-nine days following tumor implantation, 1 group of unoperated rats was orchiectomized while the rats implanted subsequent to orchiectomy were repleted with pharmacological doses of testosterone. At 2 and 4 weeks following treatment, half the original number of rats from each group were sacrificed and the growth rate (doubling time), per cent of aneuploid cells and androgen receptor levels (total, cytoplasmic and nuclear) were determined for each tumor. Orchiectomy increased tumor doubling time, while testosterone repletion decreased it, demonstrating the hormonal dependence of this tumor strain. Orchiectomy also decreased the levels of aneuploid cells in the tumor; however, repletion of testosterone to rats orchiectomized prior to implantation did not restore the aneuploid cell number to control levels. A sensitive indicator of the hormonal status of the tumor was the per cent of androgen receptors in the nucleus. Tumors grown in rats orchiectomized after implantation had the lowest percentage of androgen receptor in the nucleus while orchiectomized rats repleted with testosterone had the highest percentage. Comparison of the levels of androgen receptors in the tumors from the various groups (androgen receptor per gram of tissue) unexpectedly revealed that tumors grown in the orchiectomized rats had slightly higher total receptor levels than did control tumors, while the tumors of orchiectomized rats repleted with testosterone had lower amounts than did the control tumors. In contrast to these findings, the prostates of orchiectomized rats replenished with testosterone had higher levels of total androgen receptor than did the prostates of control rats.