INSULIN-LIKE GROWTH FACTOR-I (IGF-I) MAY NOT BE ESSENTIAL FOR OVARIAN FOLLICULAR DEVELOPMENT - EVIDENCE FROM IGF-I DEFICIENCY

Insulin-like growth factor-I (IGF-I) stimulates growth and differentiation in follicular granulosa cells (GC). To examine whether this effect is prerequisite to human folliculo-genesis, a patient with Laron-type dwarfism (IGF-I deficiency secondary to GH receptor abnormality) was examined while undergoing in vitro fertilization treatment. Despite low levels of IGF-I in serum and follicular fluid (< 3 and < 2 nmol/L) and verv high levels of IGF-I-binding protein, the patient developed normal ovarian follicles. After the administration of GnRH analog (GnRHa) and human menopausal gonadotropin in a dose similar to that used in normovulatory women, estradiol (E2) levels reached above 5000 pmol/L on the day of hCG administration, and mature fertilizable oocytes were retrieved during ovum pick-up. The patient's GC E2 Production, tested in a primary culture, did not respond to IGF-I after 4 days of incubation, while control cultures showed a significant increase. Only after a priming period of 7 days did IGF-I have a significant effect on E2 production, as observed in the patient's GC culture. This delayed response suggests that the patient's GC were not exposed in vivo to IGF-I. Our data support the view that IGF-I is not required for normal follicular development, but is, rather, a nonessential modulator of FSH action.