SECRETION OF INSULIN-LIKE GROWTH FACTOR-I (IGF-I) AND IGF-BINDING PROTEINS FROM BOVINE MAMMARY TISSUE INVITRO

In vitro, insulin-like growth factor-I (IGF-I) promotes both growth and development of bovine mammary tissue. In vivo, the effects of IGF-I may encompass endocrine, paracrine or autocrine mediation. We addressed the possibility of paracrine/autocrine effects of IGF-I in the mammary gland by examining the in-vitro secretion of IGF-I and IGF-binding proteins (IGFBPs) from bovine mammary tissue. Bovine mammary explants from pregnant non-lactating and lactating non-pregnant animals were found to synthesize and secrete IGF-I and IGFBPs. Mammary acini cultures, representative of mammary secretory epithelia, secreted both IGF-I and IGFBP, but synthesized only IGFBP. Concentrations of IGF-I in conditioned media from explants were 1.54 and 0.72 fmol/mu-g DNA for pregnant and lactating animals respectively. Concentrations of IGFBPs in conditioned media from explants were similar for both physiological states at 2529 pmol I-125-labelled IGF-I bound/mu-g DNA. Ligand/Western blotting procedures identified four IGFBPs of 29, 33, 37 and 44 kDa for acini cultures and five IGFBPs of 28, 31, 36, 44 and 46 kDa for explant cultures. Similar affinities for IGF-I and IGF-II were shown by IGFBP, using I-125-labelled recombinant human IGF-I as the competing ligand (median effective dose (ED50) of 0.085 pmol). When I-125-labelled bovine IGF-II was used as the ligand, only bovine IGF-II (ED50 of 0.25 pmol) inhibited binding. The addition of prolactin, insulin and cortisol, with or without GH, did not affect secretion of either IGF-I or IGFBP. This report describes the ability of normal mammary tissue to synthesize and secrete IGF-I and IGFBPs.