EVIDENCE THAT THE MAMMARY FAT PAD MEDIATES THE ACTION OF GROWTH-HORMONE IN MAMMARY-GLAND DEVELOPMENT

Recent evidence from our laboratory suggests that GH and insulinlike g rowth factor I (IGF-I) mediate glandular mammary development together with estrogen. It has also been well established that both stromal and epithelial elements must interact for mammary glandular development t o occur. To determine whether the effect of GH is mediated by the stro mal or epithelial tissue, we set up the following experiment. Bovine G H (bGH; 100 mu g) or BSA (as a control), without or with estradiol (E- 2), was injected ip into sexually immature female rats that were hypop hysectomized and oophorectomized. Mammary glands and subscapular fat p ads were removed from the animals. The mammary glands were divided int o two parts: a gland-free fat pad and remaining glandular tissue. The end point of bGH activity was induction of IGF-I messenger RNA (mRNA). This was determined quantitatively by solution hybridization and also by RT-PCR. We found that the effects of GK on stimulation of IGF-I mR NA in the gland-free mammary fat pad and the remainder of the mammary gland were similar (3.6- vs. 3.9-fold, respectively; P < 0.001). In bo th sorts of mammary tissue, bGH was found to synergize with E-2 in the induction of IGF-I mRNA (5.8- vs. 5.3-fold; P < 0.001). There was als o an increase in IGF-I mRNA in subscapular fat pads in response to 100 mu g bGH (5.3-fold; P < 0.001); however, no synergism between bGH and E-2 was found. These data indicate that bGH works as well on mammary stromal tissue as on tissue with glands and suggests that GH acts on t he stromal compartment of the mammary gland to induce IGF-I mRNA and p ossibly IGF-I itself, which, in turn, causes differentiation of epithe lial ducts into terminal end buds. These data also might explain why m ammary epithelium is also able to differentiate in nonmammary fat pads when transplanted there.