Metabolism of prolactin in mice with a high incidence of mammary tumours: evidence for greater conversion into a non-immunoassayable form.

Monomeric mouse prolactin containing small amounts of 125I-labelled prolactin was administered to adult female mice of a high (C3H/St) and low (C57BL/St) mammary tumour strain. Their endogenous prolactin had been suppressed with 2-bromo-alpha-ergocryptine. The chromatographic profile, on Sephadex G-100, of prolactin in the serum of mice injected with mouse prolactin was compared by direct measurement (radioactivity count) and by radioimmunoassay (RIA) at several intervals after injection. With both methods, the injected hormone was found in the serum in predominantly two molecular sizes, the so-called 'big' and 'little' forms. Although 'little' prolactin in both strains constituted a constant 80% of the total hormone at most intervals by direct measurement, it comprised a comparatively smaller proportion by RIA. In addition, the RIA-determined 'little' prolactin, after reaching maximum levels at 15 min, progressively decreased with time, the decrease being greater in the C3H/St than in the C57BL/St strain. Similar experiments with mouse growth hormone revealed no such discrepancies between the radioactivity counts and the RIA measurements. A fraction of both 'big' and 'little' forms in the C3H/St strain failed to precipitate completely after the material had been incubated with an antiserum to mouse prolactin. These results demonstrate that the prolactin injected into mice is metabolized in serum into two non-immunoreactive forms, one that elutes with the same elution volume on Sephadex G-100 column as the monomer and the other that elutes as the 'big' form. Furthermore, the loss of immunoreactivity of monomeric mouse prolactin is greater in the high-tumour C3H/St strain than in the low-tumour C57BL/St strain. Endogenous immunoreactive prolactin, on the other hand, was found mainly in the 'big' form in the serum of female mice of the C3H/St strain under basal conditions, whereas it was present only in the 'little' form in comparable mice of the C57BL/St strain, even though pituitary extracts of both strains contained mainly the 'little' form. These results support the concept that monomeric prolactin in the systemic circulation of the tumour-prone C3H/St strain is largely in a non-immunoreactive form.