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 a nd 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 investig ated whether IGF-I, like GH, required estradiol (E(2)) to act or wheth er IGF-I could substitute for both GH and E(2). The effects of IGF-I w ere tested in the presence and absence of E(2). Elvax pellets containi ng IGF-I or des(1-3) IGF-I were implanted into right lumbar mammary gl ands of sexually immature, hypophysectomized, oophorectomized female r ats, 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, h ad 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 ma mmary development, similar to that noted when E(2) was given along wit h 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. Th ese 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) o n mammary development may take place at multiple sites. If locally pro duced IGF-I does indeed mediate the action of GH in mammary developmen t, 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.