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 folliculogenesis, 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 (less than 3 and less than 2 nmol/L) and very 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 pickup. 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.
Dor
J
J
Department of Obstetrics and Gynecology, Sheba Medical Center, Tel Hashomer, Israel.
Ben-Shlomo
I
I
Lunenfeld
B
B
Pariente
C
C
Levran
D
D
Karasik
A
A
Seppälä
M
M
Mashiach
S
S
D000328:Adult; D002478:Cells, Cultured; D004392:Dwarfism / Q000503:physiopathology*; D004958:Estradiol / Q000097:blood; D005260:Female; D005307:Fertilization in Vitro; D006107:Granulosa Cells / Q000166:cytology / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000172:deficiency* / Q000502:physiology; D006080:Ovarian Follicle / Q000502:physiology / Q000503:physiopathology*; D011374:Progesterone / Q000097:blood; D012016:Reference Values
D007328:Insulin; D011374:Progesterone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I