Effects of insulin-like growth factor-I on follicle growth, oocyte maturation, and ovarian steroidogenesis and plasminogen activator activity in the rabbit.
We examined the effects of insulin-like growth factor (IGF)-I on follicular growth, oocyte maturation, and ovarian steroidogenesis and plasminogen activator (PA) activity in vitro, using a perfused rabbit ovary preparation in order to determine whether the follicle-stimulating effects of growth hormone (GH) are mediated by IGF-I. The addition of IGF-I to the perfusate stimulated follicular growth and the resumption of meiosis in follicular oocytes in a dose-dependent manner. There was no significant difference in the production of progesterone by perfused rabbit ovaries between IGF-I-treated and control ovaries, whereas IGF-I increased the production of estradiol (E2) by perfused rabbit ovaries in a dose-dependent manner. The concomitant addition of a monoclonal antibody recognizing the type I IGF receptor, alpha IR-3, to the perfusate significantly blocked IGF-I-stimulated follicular growth, oocyte maturation, and E2 production. Intrafollicular PA activity increased significantly 4 h after exposure to 10 or 100 ng/ml of IGF-I and reached maximal levels at 6 h. The percentage increase in follicle diameter at 6 h after exposure to IGF-I was significantly correlated with the intrafollicular PA activity. Treatment with GH resulted in a 2.7-fold increase in intrafollicular levels of IGF-I mRNA. The binding of [125I]-IGF-I to rabbit ovarian membrane preparations was inhibited by unlabeled IGF-I and IGF-II in a concentration-dependent manner. The relative affinity of the IGF-I receptor for IGF-I, IGF-II, and insulin was typical of type I binding (IGF-I > IGF-II > insulin). Affinity cross-linking of ovarian membranes with [125I]-IGF-I revealed a radiolabeled band corresponding to a molecular weight of 135,000, the alpha subunit of the type I IGF receptor. This band was totally displaced by IGF-I and alpha IR-3. It was concluded that IGF-I stimulated follicular development, E2 production, and oocyte maturation by interacting with its specific receptor located in rabbit ovarian membranes.
Yoshimura
Y
Y
Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan.
Ando
M
M
Nagamatsu
S
S
Iwashita
M
M
Adachi
T
T
Sueoka
K
K
Miyazaki
T
T
Kuji
N
N
Tanaka
M
M
D000818:Animals; D004958:Estradiol / Q000096:biosynthesis; D005260:Female; D013006:Growth Hormone / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D009865:Oocytes / Q000254:growth & development*; D006080:Ovarian Follicle / Q000254:growth & development*; D010053:Ovary / Q000378:metabolism*; D010960:Plasminogen Activators / Q000378:metabolism*; D011374:Progesterone / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D013256:Steroids / Q000096:biosynthesis*
D007457:Iodine Radioisotopes; D012333:RNA, Messenger; D013256:Steroids; D011374:Progesterone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D017526:Receptor, IGF Type 1; D010960:Plasminogen Activators