Prolactin receptors in N-nitroso-N-methylurea-induced rat mammary tumors: relationship to tumor age and down-regulation in short-term explant culture.

Mammary tumors were induced by N-nitrosomethylurea (NMU) in young female Sprague-Dawley rats and time of appearance of the tumors was recorded daily. A total of 41 tumors of different ages (7 to 110 days old) were removed and prolactin (PRL) receptors were measured using [125I] human growth hormone (hGH) (equipotent lactogenic activity to oPRL). All but one tumor contained high PRL receptor levels. However, there was a slight decline of both free and total PRL receptor levels with increasing tumor age, with total prolactin receptor levels in tumors 7-20 days old being 32.0 +/- 1.4% compared to 26.0 +/- 2.0% in tumors 66-110 days old (p less than 0.05). In addition, for 24 of these tumors which were of sufficient size, explant cultures were carried out up to 24 h in medium-199 containing insulin and cortisol in the presence or absence of 20 microgram/ml oPRL. At this concentration, an occupation of free and a reduction of total receptor levels was observed in all explant cultures. This down-regulation also appeared to vary as a function of tumor age. Total PRL receptors declined 24.9 +/- 2.3% in young tumors (7-35 days old) compared to 41.7 +/- 4.4% in tumors 50-110 days old (p less than 0.01). The present data are important in that they demonstrate that PRL receptor levels are relatively high regardless of the age of the tumor with, however, a slight decline with increased tumor age. In contrast, the responsiveness of the tumors measured by the ability of prolactin to down-regulate its own receptors is greater in older tumors.