Effect of high-dose progesterone on growth of rat mammary carcinoma.

coimplantation with a MtT or by daily administration of the tranquilizing drug, perphenazine (4-[3-(2-chborophenothiazin 10-yI)propyl]-1 -piperazineethanol) (6). MTW9-MtT is grown by coimplantation of MTW9 with MtTW10, a MtT which secretes prolactin, growth hormone, and probably ACTH (5). MTW9-MtT stops growing after ovaniec tomy but does not regress; regression occurs after surgical removal of the MtT when serum prolactin falls to normal. MTW9-P is grown by administration of perphenazine to rats inoculated with MTW9 and, in contrast to MTW9-MtT, re gresses after ovaniectomy whether serum prolactin is normal or high (6). MTW9-MtT and MTW9-P are identical by light microscopy but differ in pnobactinand estradiol receptor con tent(4, 19). Early observations concerning growth of MTW9-MtT in ovani ectomized rats showed that ovarian hormones were required for growth. Ovariectomy at the time of tumor implantation or shortly thereafter prevented mammary tumor growth. Daily administration of estradiol, progesterone, or a combination of both steroids that was started at the time of tumor implantation allowed mammary tumor growth to occur. Greater tumor growth occurred in ovaniectomized rats receiving only progesterone from time of tumor implantation than in rats receiving only estradiol and indicated that progesterone, under the appropri ate experimental conditions, can stimulate growth of MTW9MtT (15). These studies, the reports of Huggins et a!., and other studies, showing stimulation (8—i 1) and inhibition (14, 20, 23) of carcinogen-induced mammary tumor growth by progester one, led us to reexamine the influence of progesterone in the growth of MTW9 mammary tumors. We recently reported that implantation of MtTW10 into rats bearing MTW9-PD completely prevents ovaniectomy-induced tumor regression. Attempts to simulate the endocrine environ ment of MtT-bearing rats by administration of prolactin, growth hormone, or 17-hydroxyprogesterone caproate to rats bearing MTW9-PD failed to prevent ovaniectomy-induced regression and bedus to suggest that MtTW10 secretes a substance other than prolactin which inhibits ovaniectomy-induced regression (5). We now report that progesterone affects the growth of MTW9 mammary tumors in several ways that differ from the early studies of MacLeod et al. (15) using MTW9 and from those of Huggins et aI. and others using carcinogen-induced mammary tumors (1, 8—1). It will be shown that progesterone prevents ovaniectomy-induced regression of MTW9-PD and also permits continued growth of MTW9-MtT in ovaniectomized rats. Pro gesterone is the only hormone tested thus far that prevents ovaniectomy-induced regression of MTW9-PD.