Hormone and drug effects on growth of DMBA mammary tumours and plasma prolactin levels in adreno-ovariectomized rats

Abstract

The effects of hormone and drug treatments on plasma prolactin (PRL) levels and mammary tumour growth were investigated in rats bearing continuously growing DMBA-induced mammary tumours that responded to bilateral adreno-ovariectomy (Ax + Ox), Oestrogen (E2) administration increased both plasma PRL and tumour growth, but was unable to sustain tumour growth when the PRL level was reduced by concurrent injection of ergocornine (Eg). Perphenazine (Pz) produced a dose-related increase in plasma PRL, but stimulation of tumour growth in the absence of E2 required a minimal level of plasma PRL induced by Pz (0.15 mg/100 g body wt/day or more). Progesterone (P) (3 mg/day) alone, although without effect on PRL levels, maintained static tumour growth (i.e. it had a slight stimulatory effect) irrespective of the duration of treatment. The increase in plasma PRL levels above the basal values in the Ax + Ox controls following injections of combined P + Pz (0.1 mg/100 g/day) was sufficient to sustain static tumour growth, but not to reactivate growth. Enhancement of both plasma PRL and tumour growth did not occur until P and higher doses of Pz (0.3 mg/100 g/day) were injected jointly, this treatment, however, while unable to stimulate continuous tumour growth, was able to maintain static growth when plasma PRL was reduced by concurrent injections of P + Pz + Eg. From these findings it is postulated that the mechanism of action whereby P maintains static tumour growth is different from that of PRL and independent of circulating PRL levels.