Metabolism of Prolactin in Mice With a High Incidence of Mammary Tumours: Evidence for Greater Conversion Into a Non-Immunoassayable Form

Abstract

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.

Prolactin Plasma Levels and Its Size Heterogeneity in Acutely Uremic Rats

“…This result is in agreement with data reported by others in rats [13,14], mice [22,23] and humans [4,5,7,12,24,25], bearing in mind the species, sex and physiological state, and treatment differences.…”

“…Moreover, size heter ogeneity of PRL has been observed in serum samples of both humans and experimental animals. Three molecular species have been described, the so-called 'little', 'big' and 'big-big' PRLs (21,000-23,000, 40,000-50,000, and higher than 90,000-100,000 daltons, respectively) [1,4,5,7,[11][12][13][14][22][23][24][25][26]. The biological significance of this heter ogeneity remains uncertain, but differences in biological activity have been reported [4,5], Although in acutely uremic rats [18] rPRL plasma levels do not seem to be affected by uremia in itself, it might occur that the uremic environment could in some way influence the size heterogeneity of the circulating rPRL, affecting the extent to which larger forms of PRL are released by the pituitary into circulation and/or mod ifying the relationship that seems to exist between little and big-big PRLs [11,22],…”

Tissue histopathology, clinical chemistry and behaviour of adult comt‐gene‐disrupted mice

“…It is noteworthy that we did not see any single mammary carcinoma in the mice. It is well known that some mouse strains develop mammary tumours more or less spontaneously on aging but evidently this strain was resistant to such a development (Gad et al, 1977;Sinha and Baxter, 1979 induced by total COMT inhibition were seen (Frith et al, 1980;Wolford et al, 1986;Loeb and Quimby, 1999). Also, the levels of catecholamines in plasma were not significantly increased in COMT-deficient mice in spite of high DHPG levels.…”

Serum, pituitary and urine concentrations of prolactin and growth hormone in eight strains of mice with varying incidence of mammary tumors

“…Rather, developing mammary tumor in some cases may involve subtle abnormalities in the metabolism of the hormone. Immunoreactive prolactin of several molecular sizes have been found to circulate in the blood (Suh and Frantz, 1974;Sinha and Baxter, 19796). We have observed that mice metabolize aportion of the injected prolactin into a non-immunodetectable form in their circulation, and the hightumor C3H/St strain does so to a greater extent than the low-tumor C57BL/St strain (Sinha and Baxter, 19796).…”

“…Immunoreactive prolactin of several molecular sizes have been found to circulate in the blood (Suh and Frantz, 1974;Sinha and Baxter, 19796). We have observed that mice metabolize aportion of the injected prolactin into a non-immunodetectable form in their circulation, and the hightumor C3H/St strain does so to a greater extent than the low-tumor C57BL/St strain (Sinha and Baxter, 19796). In addition, we have discovered a structural variant of prolactin in the mouse pituitary which does not cross-react with an antiserum to the major form of mouse prolactin, the antiserum that is used in our present radioimmunoassay (Sinha and Baxter, 1979~).…”