Comparison of the facilitative roles of insulin and insulin-like growth factor I in the functional differentiation of granulosa cells: in vitro studies with the porcine model.
The facilitative effects of insulin and IGF-I were compared in vitro with regard to induction of differentiated functions of porcine granulosa cells. The monolayers were maintained under serum-free conditions in the absence or presence of porcine FSH (20 micrograms/l), with or without graded doses of insulin or IGF-I. Concurrent treatment with IGF-I and FSH produced morphological differentiation and augmented LH/hCG receptor binding together with an enhancement in progesterone and estradiol secretion relative to treatment with FSH alone. IGF-I alone was incapable of exhibiting these effects. Insulin synergized with FSH to facilitate the granulosa cell functions except estradiol secretion. Maximal effective dose of IGF-I was 100 micrograms/l which is within the physiological concentration in vivo, whereas that of insulin was 1.0 mg/l, which is 1000-fold higher than the physiological level. Although the maximal effective doses of IGF-I and insulin produced a comparable increment in progesterone secretion and LH/hCG receptor induction, combined treatment with IGF-I and insulin did not prove additive. [125I]IGF-I binding revealed that specific IGF-I receptors with two classes of binding sites are present on porcine granulosa cells. No distinct differences were detected between IGF-I receptors of granulosa cells from small, medium and large follicles. Insulin was approximately 100-fold less active than IGF-I in competing for [125I]IGF-I binding. These findings suggest that porcine granulosa cells possess specific IGF-I binding sites which may mediate the cytodifferentiative actions of insulin-like peptides. Since IGF-I is more potent than insulin in amplifying the actions of FSH and maximally exerts the cytodifferentiative effects at the physiological concentration, it is likely that IGF-I plays the more important role in granulosa cell differentiation in synergy with FSH.
Maruo
T
T
Department of Obstetrics and Gynecology, Kobe University School of Medicine, Japan.
Hayashi
M
M
Matsuo
H
H
Ueda
Y
Y
Morikawa
H
H
Mochizuki
M
M
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D004958:Estradiol / Q000378:metabolism; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects* / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D011374:Progesterone / Q000378:metabolism; D011972:Receptor, Insulin / Q000187:drug effects; D011967:Receptors, Gonadotropin / Q000187:drug effects; D011974:Receptors, LH / Q000187:drug effects; D017451:Receptors, Somatomedin; D013002:Somatomedins / Q000494:pharmacology*; D013552:Swine
D007328:Insulin; D011967:Receptors, Gonadotropin; D011974:Receptors, LH; D017451:Receptors, Somatomedin; D013002:Somatomedins; D011374:Progesterone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D011972:Receptor, Insulin