Studies on rat luteal cell response to insulin-like growth factor I (IGF-I): identification of a specific cell membrane receptor for IGF-I in the luteinized rat ovary.
Insulin-like growth factor-I (IGF-I) has been shown to stimulate biosynthesis of progesterone and other differentiated functions of granulosa cells. The presence of the IGF-I receptor messenger RNA and IGF-I receptor as well as the role of IGF-I in the amplification of gonadotropin action in luteinized rat ovarian cells were assessed in the present study. Rat ovarian luteal tissue were obtained on day 6 of pseudopregnancy. After collagenase dispersion, luteal cells were cultured with or without IGF-I for 72 h in a serum-free medium in the absence or presence of human CG (100 ng/ml), 8-bromo-cAMP (1 mM), and 25-OH cholesterol (30 micrograms/ml). IGF-I alone increased (P less than 0.01) progesterone secretion 47% over controls. When combined with hCG the increase in progesterone secretion was enhanced 6-fold (P less than 0.001) over controls. The effects of 8 bromo-cAMP on progesterone secretion also was amplified (P less than 0.001) when IGF-I was present in the medium. When 25-OH cholesterol, a diffusable substrate for steroidogenesis, was included in the incubation medium along with IGF-I, progesterone secretion was enhanced significantly (P less than 0.01) over controls and either treatment alone. Binding studies performed with ovarian luteal cell membranes in the ovary revealed a dissociation constant of 0.94 nM for the IGF-I receptor. Autoradiograms from affinity labeling studies revealed a band corresponding to 132 Kd which is characteristic for the alpha-subunit of the type I IGF receptor. Northern blot analysis showed the presence of a major transcript at approximately 11 kilobases, which agrees with the size of the IGF-I receptor messenger RNA. In conclusion, we provide evidence for the fact that IGF-I regulates differentiated functions of the corpus luteum through interaction with specific high affinity IGF-I receptors.
Talavera
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Department of Obstetrics/Gynecology, University of Michigan Medical School, Ann Arbor 48109-0278.
Menon
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D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D003338:Corpus Luteum / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006888:Hydroxycholesterols / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D008970:Molecular Weight; D010053:Ovary / Q000187:drug effects / Q000502:physiology*; D011374:Progesterone / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D017451:Receptors, Somatomedin
D006063:Chorionic Gonadotropin; D006888:Hydroxycholesterols; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D011374:Progesterone; D007334:Insulin-Like Growth Factor I; C007997:25-hydroxycholesterol