EFFECTS OF CONSTANT INFUSION WITH INSULIN-LIKE GROWTH-FACTOR-I (IGF-I) TO IMMATURE FEMALE RATS ON BODY-WEIGHT GAIN, TISSUE-GROWTH, AND SEXUAL FUNCTION - EVIDENCE THAT SUCH TREATMENT DOES NOT AFFECT SEXUAL-MATURATION OR FERTILITY

Plasma levels for insulin-like growth factor-1 (IGF-I) steadily increa se in female rats between 20 and 40 d of life, and this increase is in timately related to the well-known growth spurt occurring at this age. Since specific actions of IGF-I related to sexual function have been described at the ovarian and hypothalamic levels, an endocrine role of rising circulating IGF-I levels during sexual maturation cannot be ex cluded. Therefore, the impact of adult-type plasma IGF-I levels during the juvenile age, on body weight (BW) gain, growth of several organs, sexual development, and fertility has been evaluated. Female Sprague- Dawley rats were infused with rhIGF-I (2 and 4 mu g/g BW/d, using Alze t minipumps), between 20 and 41 d of life. When infusing 2 mu g/g BW/d , plasma levels for IGF-I were increased 1.5- to 2-fold over controls at all ages studied. They were further increased with the higher dosag e, but only after 35 d of age. Plasma levels for insulin-like growth f actor binding protein (IGFBP)-1 to -3 were clearly increased. BW gain was significantly increased, but only with the higher dosage. Tail len gth was never modified. In contrast, a growth acceleration for spleen, kidneys, adrenals, and ovaries was observed with both dosages. The ov arian weight of treated animals represented approx 140% of control ani mals with the 4 mu g/g BW/d dosage. Histology of the enlarged ovaries did not reveal any abnormalities. No meaningful modification of the ti ming of vaginal opening was observed, and fertility was not compromise d by previous rhIGF-I infusion during the 20-41 d age period. In summa ry, early exposure to increased (adult-like) plasma IGF-I levels did n ot modify BW gain or tail length, but affected the development of sple en, kidneys, adrenals, and ovaries. Exposure to supraphysiological pla sma IGF-I levels (>1200 ng/mL), accelerated BW gain and increased the weight of all organs studied. No signs of precocious sexual maturation were seen and fertility was normal. In conclusion, prematurely increa sed plasma IGF-I levels affected somatotropic parameters, but not the onset of sexual function.