EXPRESSION OF COMPONENTS OF THE INSULIN-LIKE GROWTH-FACTOR SYSTEM IN PIG MAMMARY-GLANDS AND SERUM DURING PREGNANCY AND PSEUDOPREGNANCY - EFFECTS OF ESTROGEN

To gain insight into the involvement and interactions of the insulin-l ike growth factors (IGFs) and oestrogen in mammary growth and differen tiation, the temporal expression of mammary mRNAs encoding components of the IGF system in pregnant and pseudopregnant pigs was examined. Ps eudopregnant pigs received 5 mg oestradiol valerate or vehicle daily f rom day 45 after oestrus and underwent mammary biopsy on days 60, 90 o r 112. In mammary tissue of pregnant pigs, steady-state levels of the mRNAs encoding IGF-I, IGF-II and type-I IGF receptor as well as the le vels of the membrane-associated type-II IGF receptor were higher durin g the early phase of mammogenesis (less-than-or-equal-to day 45) than during the subsequent stages of mammary development. Mammary IGF-I, IG F-II and type-I receptor mRNAs were expressed at their lowest levels a round day 90 of pregnancy (20-40% of those for day 30 of pregnancy) co incident with the onset of beta-casein mRNA accumulation. Mammary IGF- binding protein-2 (IGFBP-2) mRNA levels increased twofold during the l atter half of pregnancy, whereas the amount of IGFBP-3 mRNA declined a fter day 30 to undetectable levels by midpregnancy. Pseudopregnant pig s had reduced levels of these mRNAs (except for IGF-II) relative to th eir pregnant counterparts and this was associated with premature diffe rentiation of mammary tissue as reflected by an earlier onset of beta- casein mRNA accumulation in the former. The administration of oestradi ol valerate decreased the levels of IGF-I and type-I IGF receptor mRNA s by day 60 of pseudopregnancy, but the reverse was evident by day 112 . Oestradiol administration increased beta-casein mRNA levels in pseud opregnant pigs, but had no effect on mammary IGFBP-2 and IGFBP-3 mRNA levels. Mammary IGF content was greater in late pregnancy (greater-tha n-or-equal-to day 90) and pseudopregnancy than at early pregnancy. Ser um IGF-I and IGF-11 levels declined steadily during pregnancy and this was similar to, but not correlated with, mammary IGF mRNA levels, whe reas in pseudopregnant pigs, serum IGF concentrations did not change t emporally or in response to oestradiol. Serum IGFBP-2 levels were unal tered during pregnancy or pseudopregnancy, but serum IGFBP-3 levels de clined after day 60 of pregnancy. In pseudopregnant pigs, serum IGFBP- 3 levels did not change temporally, but declined after oestradiol trea tment. Results indicate that mammary IGF-I and type-I IGF receptor sys tems are down-regulated during pregnancy-associated differentiation of this tissue and in response to oestrogen. Locally produced (autocrine and paracrine) IGFs are likely to mediate mammogenesis, whereas oestr ogen stimulates mammary differentiation and lactogenesis in the pig. H owever, the high mammary IGF content and the reciprocal expression of mammary IGFBP-2 and IGFBP-3 mRNAs during late pregnancy suggests the i nvolvement of IGFs in lactogenesis as well.