ESTRADIOL ENHANCES THE STIMULATORY EFFECT OF INSULIN-LIKE GROWTH-FACTOR-I (IGF-I) ON MAMMARY DEVELOPMENT AND GROWTH HORMONE-INDUCED IGF-I MESSENGER-RIBONUCLEIC-ACID

Pubertal mammary development in the rat is largely dependent upon GK and estrogen. We recently showed that insulin-like growth factor-I (IGF-I) can substitute for GH in inducing mammary development in male rats, suggesting that IGF-I mediates GH action. The present study investigated whether IGF-I, like GH, required estradiol (E(2)) to act or whether IGF-I could substitute for both GH and E(2). The effects of IGF-I were tested in the presence and absence of E(2). Elvax pellets containing IGF-I or des(1-3) IGF-I were implanted into right lumbar mammary glands of sexually immature, hypophysectomized, oophorectomized female rats, with control BSA-containing pellets in the contralateral glands. After 5 days, both lumbar mammary glands were removed and examined in whole mounts for mammary development by counting terminal end buds and alveolar structures. E(2), administered in SILASTIC brand capsules, had no independent effect on mammary development. In the absence of E(2), des(1-3) IGF-I had a small, but significant, independent effect an mammary development; native IGF-I was ineffective. The addition of E(2) significantly enhanced the effects of IGF-I and des(l-l) IGF-I on mammary development, similar to that noted when E(2) was given along with GH. We also studied the effects of E(2) and/or hGH on mammary gland IGF-I messenger RNA (mRNA) in hypophysectomized castrated male animals. E(2) alone did not increase mammary gland IGF-I mRNA concentrations, but E(2) enhanced the effect of hGH on IGF-I mRNA by 4- to 6-fold. These studies indicate that IGF-I can have a small independent effect on mammary development, but like GH, E(2) is required for a full effect. They also indicate that E(2) is capable of synergizing with GH in the production or expression of IGF-I mRNA, and that the action of E(2) on mammary development may take place at multiple sites. If locally produced IGF-I does indeed mediate the action of GH in mammary development, then although E(2) is capable of enhancing the effect of GH on IGF-I mRNA, its major effect in mammary development occurs after IGF-I is produced.