Measurement of betacellulin levels in bovine serum, colostrum and milk

Betacellulin, a member of the epidermal growth factor (EGF) family, was ori ginally isolated and identified from the conditioned medium from a murine p ancreatic beta -cell carcinoma cell line. Recently, we isolated bovine beta cellulin from a growth factor enriched cheese whey extract, but there is no information on the presence of betacellulin in other biological fluids. We have cloned the cDNA for bovine betacellulin, produced recombinant betacel lulin and shown that it has a similar potency to the purified native molecu le in stimulating the proliferation of Balb/c3T3 fibroblasts. We have produ ced a polyclonal antiserum to bovine betacellulin which did not cross-react with EGF or transforming growth factor-alpha (TGF-alpha). The antibody was used in a homologous RIA that was able to detect betacellulin in pooled bo vine colostrum sampled during the first 3 days after calving (2.30 +/- 0.11 ng/ml mean +/- S.E.M.; n=6), in bovine milk soluble fraction (1.93 +/- 0.6 4 ng/ml mean +/- S.E.M.; n=5) and in bovine cheese whey (2.59 +/- 0.16 ng/m l mean +/- S.E.M.; n=3). The betacellulin concentration in foetal bovine se rum (FBS) (3.68 +/- 0.59 ng/ml mean +/- S.E.M.; n=6) greatly exceeded that of betacellulin in serum from male calves 1 and 5 weeks of age (0.53 +/- 0. 15 ng/ml and 0.70 +/- 0.09 ng/ml respectively; mean +/- S.E.M.; n=9). Betac ellulin measured in the serum of these same animals when aged between 27 an d 43 weeks was below the detection limits of the RIA. Sera from 10 out of 3 6 unmated heifers contained betacellulin levels within the detection limits of the assay (0.433 +/- 0.06 ng/ml mean +/- S.E.M.; n=10). The presence of betacellulin in bovine colostrum and milk suggests that it plays a role in the growth and development of the neonate and/or mammary gland function. T he results also show that betacellulin is undetectable in the castrated adu lt male circulation. Additionally, although present in very low amounts, se rum betacellulin could be under hormonal regulation in the female, since be tacellulin was detected in sera from 27% of the unmated heifers examined in this study. The high levels of betacellulin detected in FBS relative to ne wborn and adult serum suggests a possible endocrine role for this growth fa ctor in the bovine foetus.