Effect of follicle-stimulating hormone on insulin-like growth factor-I-stimulated rat granulosa cell deoxyribonucleic acid synthesis.
Granulosa cells from diethylstilbestrol-treated immature rats were cultured in a defined medium on collagen-coated plates. Thymidine incorporation was significantly increased by insulin (ED50, 656 +/- 110 ng/ml) and insulin-like growth factor (IGF-I; ED50, 95 +/- 10 ng/ml). Insulin and IGF-I stimulations were amplified by methylisobutylxanthine an inhibitor of phosphodiesterase activity. The effect of both peptides were also enhanced by low doses of (Bu)2cAMP (0.2-1 mM). In contrast, higher concentrations were inhibitory. Similarly, FSH produced a biphasic enhancement of the insulin- and IGF-I-stimulated DNA synthesis. Maximal effects (2- to 6-fold increases) were observed with the lower doses (2-20 ng/ml) of the gonadotropin. FSH enhancement of IGF-I-stimulated DNA synthesis was dependent on cell density. Plating densities of 3-5 x 10(5) cells/cm2 were required for a maximal interaction. It is concluded that FSH, acting through a cAMP-mediated pathway, may regulate granulosa cell proliferation by modulating the mitogenic effects of insulin and/or IGF-I.
Bley
M A
MA
Instituto de Biología y Medicina Experimental, Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, U.B.A., Buenos Aires, Argentina.
Simón
J C
JC
Estévez
A G
AG
de Asúa
L J
LJ
Barañao
J L
JL
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis*; D004261:DNA Replication / Q000187:drug effects*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D006107:Granulosa Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007700:Kinetics; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology
D011994:Recombinant Proteins; D003994:Bucladesine; D007334:Insulin-Like Growth Factor I; D005640:Follicle Stimulating Hormone; D004247:DNA; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine