A cleaved form of prolactin in the mouse pituitary gland: identification and comparison of in vitro synthesis and release in strains with high and low incidences of mammary tumors.

A form of rat PRL with a clip in its large disulfide loop, the so-called cleaved PRL, has been reported to have a greater mammogenic activity than the intact molecule. This study was undertaken to investigate the presence of cleaved PRL in the mouse pituitary gland with the purpose of correlating its concentrations with the incidence of mammary tumors. We could identify this molecule in the mouse pituitary by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, although its concentration was not high enough for ready detection in crude extracts of pituitary tissues. Cleaved mouse PRL and its 16 K and 8 K fragments cross-reacted with antibodies to the intact molecule and, thus, cannot be differentiated from the latter by RIA. When pituitaries were incubated for 6 h with 14C-labeled amino acids, cleaved PRL from the pituitaries of male mice incorporated more radioactive amino acids than the corresponding molecules from female mice. However, treatments such as ovariectomy, ovariectomy plus estradiol benzoate, perphenazine, and 2-Br-alpha-ergocryptine affected the concentration of labeled cleaved PRL in the same manner as they did that of the intact molecule. The ratio of labeled cleaved PRL to the labeled intact molecule in mice with a high incidence of mammary tumors (C3H/St) was not much different from that in mice with a low incidence (C57BL/6J) in pituitary plus medium. However, this ratio was slightly but consistently higher in medium from the C3H/St strain, raising the interesting question whether such a preponderance prevails in the circulation of this and other mammary tumor-prone strains as well.