Insulin-like growth factor-I (IGF-I) and IGF-II hormonal action in cultured rat granulosa cells: mediation via type I but not type II IGF receptors. 1990

E Y Adashi, and C E Resnick, and R G Rosenfeld
Department of Obstetrics/Gynecology, University of Maryland School of Medicine, Baltimore 21201.

Both insulin-like growth factor-I (IGF-I) and IGF-II have been shown to promote granulosa cell differentiation and proliferation. While both type I and type II IGF receptors have been observed in rat granulosa cells, the identity of the IGF receptor type(s) mediating IGF hormonal action remains uncertain. Whereas the role of the rat type I IGF receptor cannot be completely evaluated at this time due to the lack of specific reagents, the availability of antibodies specific for the rat type II IGF receptor (R-II-PAB1) has made studies of this receptor type possible. To validate the utility of the R-II-PAB1 antiserum at the level of the rat granulosa cell, its ability to immunoneutralize the granulosa cell type II IGF receptor was examined. Significantly, R-II-PAB1 (10-100 micrograms/ml) proved a potent inhibitor of [125I]IGF-II (but not [125I]IGF-I) binding to granulosa cell membrane preparations. Substantial, albeit finite, R-II-PAB1-mediated inhibition of the cross-linking of [125I]IGF-II was also observed. Moreover, R-II-PAB1 proved highly potent in immunoprecipitating the rat granulosa cell type II IGF receptor. In light of these observations, we have proceeded to use R-II-PAB1 to assess the functional role of the rat granulosa cell type II IGF receptor in IGF-I and IGF-II hormonal action. To this end, FSH (20 ng/ml)-primed granulosa cells were cultured for 72 h in the absence or presence of IGF-I or IGF-II (50 ng/ml) with or without increasing (receptor-active) concentrations of R-II-PAB1 (10-100 micrograms/ml). Control incubations were carried out with an ammonium sulfate precipitate of nonimmune rabbit serum dialyzed against PBS. Significantly, both R-II-PAB1 and nonimmune rabbit serum were without effect on the cytodifferentiative action of either IGF-I or IGF-II. Subject to limitations inherent to the immunoneutralizing potency of R-II-PAB1, these findings are in keeping with the notion that (inasmuch as the conventional cytodifferentiative process is concerned) the granulosa cell type II IGF receptor does not appear to participate in transmembrane IGF signalling. By inference, these findings also suggest that IGF-I and IGF-II hormonal action at the level of the granulosa cell may be exerted largely, if not exclusively, via the type I IGF receptor. Thus, the potential relevance and the functional role(s), if any, of the granulosa cell type II IGF receptor remain to be determined.

UI MeSH Term Description Entries
D007334 Insulin-Like Growth Factor I A well-characterized basic peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like, and mitogenic activities. This growth factor has a major, but not absolute, dependence on GROWTH HORMONE. It is believed to be mainly active in adults in contrast to INSULIN-LIKE GROWTH FACTOR II, which is a major fetal growth factor. IGF-I,Somatomedin C,IGF-1,IGF-I-SmC,Insulin Like Growth Factor I,Insulin-Like Somatomedin Peptide I,Insulin Like Somatomedin Peptide I
D007335 Insulin-Like Growth Factor II A well-characterized neutral peptide believed to be secreted by the LIVER and to circulate in the BLOOD. It has growth-regulating, insulin-like and mitogenic activities. The growth factor has a major, but not absolute, dependence on SOMATOTROPIN. It is believed to be a major fetal growth factor in contrast to INSULIN-LIKE GROWTH FACTOR I, which is a major growth factor in adults. IGF-II,Multiplication-Stimulating Activity,Somatomedin MSA,IGF-2,Insulin Like Growth Factor II,Insulin-Like Somatomedin Peptide II,Multiplication-Stimulating Factor,Somatomedin A,Factor, Multiplication-Stimulating,Insulin Like Somatomedin Peptide II,Multiplication Stimulating Activity,Multiplication Stimulating Factor
D011374 Progesterone The major progestational steroid that is secreted primarily by the CORPUS LUTEUM and the PLACENTA. Progesterone acts on the UTERUS, the MAMMARY GLANDS and the BRAIN. It is required in EMBRYO IMPLANTATION; PREGNANCY maintenance, and the development of mammary tissue for MILK production. Progesterone, converted from PREGNENOLONE, also serves as an intermediate in the biosynthesis of GONADAL STEROID HORMONES and adrenal CORTICOSTEROIDS. Pregnenedione,Progesterone, (13 alpha,17 alpha)-(+-)-Isomer,Progesterone, (17 alpha)-Isomer,Progesterone, (9 beta,10 alpha)-Isomer
D011956 Receptors, Cell Surface Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands. Cell Surface Receptor,Cell Surface Receptors,Hormone Receptors, Cell Surface,Receptors, Endogenous Substances,Cell Surface Hormone Receptors,Endogenous Substances Receptors,Receptor, Cell Surface,Surface Receptor, Cell
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D002462 Cell Membrane The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells. Plasma Membrane,Cytoplasmic Membrane,Cell Membranes,Cytoplasmic Membranes,Membrane, Cell,Membrane, Cytoplasmic,Membrane, Plasma,Membranes, Cell,Membranes, Cytoplasmic,Membranes, Plasma,Plasma Membranes
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D003432 Cross-Linking Reagents Reagents with two reactive groups, usually at opposite ends of the molecule, that are capable of reacting with and thereby forming bridges between side chains of amino acids in proteins; the locations of naturally reactive areas within proteins can thereby be identified; may also be used for other macromolecules, like glycoproteins, nucleic acids, or other. Bifunctional Reagent,Bifunctional Reagents,Cross Linking Reagent,Crosslinking Reagent,Cross Linking Reagents,Crosslinking Reagents,Linking Reagent, Cross,Linking Reagents, Cross,Reagent, Bifunctional,Reagent, Cross Linking,Reagent, Crosslinking,Reagents, Bifunctional,Reagents, Cross Linking,Reagents, Cross-Linking,Reagents, Crosslinking
D005260 Female Females
D005640 Follicle Stimulating Hormone A major gonadotropin secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Follicle-stimulating hormone stimulates GAMETOGENESIS and the supporting cells such as the ovarian GRANULOSA CELLS, the testicular SERTOLI CELLS, and LEYDIG CELLS. FSH consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. FSH (Follicle Stimulating Hormone),Follicle-Stimulating Hormone,Follitropin

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