Concentrations of IGF-I and IGF-II, and IGF binding proteins (IGFBP) in serum and mammary gland secretions were surveyed during the dry period and early lactation of 30 Holstein cows. Although there was a threefold drop in the concentration of IGF-I in serum from the last week of the dry period to parturition (81 +/- 7 to 24 +/- 3 ng/ml, P less than .01), there was no significant change in serum IGF-II concentration during this period (150 +/- 17 vs 173 +/- 13 ng/ml, P greater than .05). Furthermore, a 57% increase in serum IGF-I was observed from the last week of lactation to the second week of drying off (100 +/- 5 to 157 +/- 8 ng/ml, P less than .05). Changes in serum IGF-II were not observed (126 +/- 11 vs 150 +/- 10 ng/ml, respectively; P greater than .05). Although IGF-I, IGF-II, and IGFBP concentrations in mammary secretions peaked 2 wk before parturition (2.95 +/- 1.1, 1.83 +/- .6, and 7.27 +/- .76 micrograms/ml, respectively), total output/quarter was highest in colostrum (394 +/- 119, 295 +/- 132, and 2,680 +/- 1,967 micrograms/quarter, respectively). Weekly milking of two individual quarters during the dry period did not affect (P greater than .05) IGF-I or IGF-II concentration (ng/ml) or total output (microgram/quarter) and milk yield in colostrum and milk (2 wk and 7 wk) compared with the ipsilateral quarter. The data support the hypothesis that IGF-I may be transported by the mammary gland epithelium. Furthermore, the secretion mechanisms of IGF-I, IGF-II, and IGFBP by the gland may be related to each other.
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/micrograms DNA for pregnant and lactating animals respectively. Concentrations of IGFBPs in conditioned media from explants were similar for both physiological states at 2529 pmol 125I-labelled IGF-I bound/micrograms 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 125I-labelled recombinant human IGF-I as the competing ligand (median effective dose (ED50) of 0.085 pmol). When 125I-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.
The bovine mammary gland accumulates large quantities of insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) during late gestation which are secreted at parturition. The present study was conducted to determine the changes in the profiles of IGFBPs secreted by the mammary gland and in blood during late gestation and early lactation in dairy cows. Ligand blotting of serum and mammary secretions showed that IGFBPs of Mr 25,000, 30,000, 34,000, 42,000, 46,000 and greater than 200,000 were present in both fluids. The binding activity of the 42-46,000 Mr IGFBP predominated in prepartum mammary secretions and colostrum but was reduced postpartum. The binding activities of the 30,000 and 34,000 Mr IGFBPs, relative to other IGFBPs, were increased postpartum. Concentrations of IGF-I and IGF-II in mammary secretions declined from 347.1 and 181.1 nmol/litre 1 week prepartum to 0.7 and 0.3 nmol/litre 1.5 weeks postpartum. The volume of mammary secretions obtained was 0.109 litre and 6.690 litres at 1 week prepartum and 1.5 weeks postpartum respectively. In prepartum serum, the greatest binding activity was at Mr 42-46,000. The activity at this Mr decreased at parturition but was restored postpartum. The binding activities of the 30,000 and 34,000 Mr IGFBPs were increased around parturition. The 25,000 Mr IGFBP had minor activity during all periods. IGF-I concentrations decreased from 10.6 nmol/litres 1 week prepartum to 4.7 nmol/litres 1.5 weeks postpartum but IGF-II concentrations remained constant. In conclusion, IGFBP activity secreted by the mammary gland shifts from primarily Mr 42-46,000 prepartum to Mr 30,000 postpartum.(ABSTRACT TRUNCATED AT 250 WORDS)
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