Synergism or antagonism between estradiol and progesterone on the cell kinetic parameters of the MXT mouse mammary tumor.

With the use of an in vivo tritiated thymidine ([3H]dThd) nuclear labeling followed by autoradiography, the effects at different times before sacrifice of single or paired injections of 17 beta-estradiol (E2) and/or progesterone (Pg), at different concentrations, were studied in (C57BL x DBA/2f)F1 (B6D2F1) mice transplanted with the MXT hormone-sensitive mammary tumor. Uteri were chosen as controls for the methodology. With regard to MXT tumors, E2 (0.25, 2.50, or 25.00 micrograms/animal) or Pg (125, 600, or 5,000 micrograms/animal) exerts almost a similar mitogenic influence that is dose related to the former and nor for the later, at least within the range of concentrations studied here; and the mitogenic effect of Pg seems to appear earlier than that of E2. When these steroids are concomitantly given, no obvious synergistic or antagonistic effect can be observed. A second E2 administration seems to have a less pronounced effect on cell proliferation as compared to that exerted by the first injection performed 12 or 24 hours earlier. On the contrary, the repetition of a Pg treatment would rather exert an additive or even a synergistic effect on the tumoral dThd labeling indices with regard to the total duration of stimulation. When one of these two steroids is administered first, it blocks totally the mitogenic effect of the second, provided the latter is given 24 hours later. It is concluded that E2 and Pg have almost a similar mitogenic effect on the MXT tumor and that these hormones exert complex interactions that are probably very important for the growth regulation of this cancer. Further investigations are needed to better understand the precise biochemical mechanisms involved in the modulating actions of these steroids on the MXT mammary growth.