ONTOGENY AND EPITHELIAL-STROMAL INTERACTIONS REGULATE IGF EXPRESSION IN THE OVINE MAMMARY-GLAND

Although the insulin-like growth factors (IGF-I and -II) have been imp licated in the stimulation of mammogenesis, little is known of their r egulation in the mammary gland. In this study we removed epithelial ti ssue from one of the two mammary glands of 1-week-old ewe lambs and ex amined IGF-I and -II mRNA expression during postnatal development in b oth the intact mammary gland and in the gland cleared of epithelial ti ssue. Expression of IGF-I mRNA was highest at 6 and 10 weeks of age, c oincident with the prepubertal phase of rapid mammary growth, then dec lined and remained low until expression increased during late pregnanc y. IGF-I mRNA was more abundant in the mammary fat pad adjacent to par enchyma (MFP) than in the contralateral fat pad that had been surgical ly cleared of epithelium (CFP). The level of IGF-II mRNA in parenchyma was highest at 1-23 weeks of age due to an increase in the abundance of specific mRNAs. Expression was lower in the fat pads, with generall y higher levels in the intact MFP than the CFP, and in these tissues I GF-II expression was shown to increase with age between 6 and 23 weeks . We also investigated the influence of the ovary and estrogen on the expression of IGFs. While IGF-I mRNA abundance was unaffected by ovari ectomy, exogenous estrogen resulted in higher levels of expression in the MFP of ovariectomized ewes and tended to increase its level in the parenchyma of intact ewes. Ovariectomy increased IGF-II mRNA within m ammary parenchyma whereas estrogen suppressed levels in both the paren chyma and MFP. These findings demonstrate that IGF-I and -II mRNAs are expressed locally within the developing ovine mammary gland and are r egulated by stage of ontogeny, ovarian hormones, and epithelial-stroma l interaction. (C) 1998 Elsevier Science Ireland Ltd.