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Evidence That the Mammary Fat Pad Mediates the Action of Growth Hormone in Mammary Gland Development

Departments of Medicine, Urology, and Biochemistry, Department of Veterans Affairs Medical Center and New York University Medical Center, New York, New York 10010

Address all correspondence and requests for reprints to: David L. Kleinberg, M.D., Room 16043W, DVA Medical Center, 423 East 23rd Street, New York, New York 10010. E-mail: kleind02{at}popmail.med.nyu.edu

Recent evidence from our laboratory suggests that GH and insulin-like growth 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 to occur. To determine whether the effect of GH is mediated by the stromal or epithelial tissue, we set up the following experiment. Bovine GH (bGH; 100 µg) or BSA (as a control), without or with estradiol (E₂), was injected ip into sexually immature female rats that were hypophysectomized and oophorectomized. Mammary glands and subscapular fat pads were removed from the animals. The mammary glands were divided into 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 GH on stimulation of IGF-I mRNA 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 both sorts of mammary tissue, bGH was found to synergize with E₂ in the induction of IGF-I mRNA (5.8- vs. 5.3-fold; P < 0.001). There was also an increase in IGF-I mRNA in subscapular fat pads in response to 100 µg bGH (5.3-fold; P < 0.001); however, no synergism between bGH and E₂ 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 the stromal compartment of the mammary gland to induce IGF-I mRNA and possibly IGF-I itself, which, in turn, causes differentiation of epithelial ducts into terminal end buds. These data also might explain why mammary epithelium is also able to differentiate in nonmammary fat pads when transplanted there.

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