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 of fertility.
Plasma levels for insulin-like growth factor-I (IGF-I) steadily increase in female rats between 20 and 40 d of life, and this increase is intimately related to the wellknown 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 excluded. 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 micrograms/g BW/d, using Alzet minipumps), between 20 and 41 d of life. When infusing 2 micrograms/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 dosage, but only after 35 d of age. Plasma levels for insulin-like growth factor binding protein (IGFBP)-1 to -3 were clearly increased. BW gain was significantly increased, but only with the higher dosage. Tail length was never modified. In contrast, a growth acceleration for spleen, kidneys, adrenals, and ovaries was observed with both dosages. The ovarian weight of treated animals represented approx 140% of control animals with the 4 micrograms/g BW/d dosage. Histology of the enlarged ovaries did not reveal any abnormalities. No meaningful modification of the timing of vaginal opening was observed, and fertility was not comprised by previous rhIGF-I infusion during 20-41 d age period. In summary, early exposure to increased (adult-like) plasma IGF-I levels did not modify BW gain or tail length, but affected the development of spleen, kidneys, adrenals, and ovaries. Exposure to supraphysiological plasma 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 increased plasma IGF-I levels affected somatotropic parameters, but not the onset of sexual function.
Gruaz
N M
NM
Department of Pediatrics, University of Geneva School of Medicine, Switzerland.
d'Allèves
V
V
Charnay
Y
Y
Skottner
A
A
Ekvärn
S
S
Fryklund
L
L
Aubert
M L
ML
D000818:Animals; D015153:Blotting, Western; D005260:Female; D006128:Growth / Q000187:drug effects*; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism; D006801:Humans; D015918:Infusion Pumps, Implantable; D018969:Insulin-Like Growth Factor Binding Proteins / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D010053:Ovary / Q000033:anatomy & histology / Q000254:growth & development; D010902:Pituitary Gland / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012741:Sexual Maturation / Q000187:drug effects*; D013154:Spleen / Q000033:anatomy & histology / Q000254:growth & development; D013623:Tail / Q000187:drug effects / Q000254:growth & development; D015430:Weight Gain / Q000187:drug effects*
D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone