Differential effects of retinoids on proliferation of bovine mammary epithelial cells in collagen gel culture

The effects of increasing concentrations of retinol. retinal and retinoic a cid on proliferation of bovine mammary epithelial cells were investigated i n collagen gel cultures. All retinoids significantly inhibited proliferatio n of mammary epithelial cells. The relative inhibitory potency of the retin oids was: retinoic acid > retinal > retinol. Maximal inhibition at 10 mug/m l corresponded to a 75-95% inhibition of proliferation obtained iii basal m edium. Retinol. retinal and retinoic acid also inhibited proliferation of c ells growth-stimulated with insulin-like growth factor-I (IGF-I). Retinoids in highest concentrations (10 mug/ml) inhibited 68-85% of proliferation of cells obtained in culture medium containing 25 ng IGF-I/ml. Retinol and re tinoic acid also inhibited proliferation of cells growth-stimulated by insu lin and other growth factors fron) the IGF growth factor family (des(1-3)IG F-1 and IGF-II). as well as growth factors from the epidermal growth factor family (EGF and TGF-alpha), with retinoic acid being more effective than r etinol, At a concentration of 100 ng/ml, retinol and retinoic acid inhibite d respectively 24-38 and 44-52% of mammary cell proliferation stimulated by growth factors of the IGF family, and at 10000 ng/ml, 61-71% of cell proli feration was inhibited. The growth-stimulating effect of insulin. EGF and T GF-alpha, was inhibited 42-64% by retinol and retinoic acid at 100 ng/ml, a nd 64-84% at 10000 ng/ml. The present results show that retinol, retinal an d retinoic acid are potent inhibitors of bovine mammary epithelia] cell pro liferation. It is suggested that retinoids may have concentration-dependent roles in regulation of pubertal mammary growth and development. indicating that the milk yield potential of heifers may be affected by vitamin A stat us.