The release of insulin-like growth factor-I by luteinized human granulosa cells in vitro: regulation by growth hormone, oxytocin, steroids and cAMP-dependent intracellular mechanisms.
The aim of the present experiments was to demonstrate the release of insulin-like growth factor-I (IGF-I) by human granulosa cells, and to examine the role of growth hormone (GH), oxytocin, steroids and cAMP-dependent intracellular mechanism in its control. A significant accumulation of IGF-I in a serum-supplemented medium in which the human granulosa cells were cultured for 4 days was observed. The concentration of IGF-I in the medium was particularly high at 3 and 4 days of culture. The addition of GH (1-10,000 ng/ml) to the medium increased IGF-I secretion by the cells. A higher GH dose (100,000 ng/ml) was inhibitory. Oxytocin stimulated IGF-I release at doses of 10-10,000 ng/ml. Dibutyryl-cAMP, isobutyl-methyl-xanthine (inhibitor of cAMP catabolism) or forskolin (stimulator of cAMP production) inhibited IGF-I output at these doses. Additions of progesterone (1-1,000 ng/ml) did not affect IGF-I release, whilst adrostenedione and estradiol were stimulatory at doses of 1, 10, 100, 1,000 ng/ml and 10, 100 and 1,000 ng/ml respectively. Testosterone inhibited IGF-I at a dose of 1,000 ng/ml but not at lower doses (1, 10 or 100 ng/ml). Blockade of estradiol (but not of testosterone) in the medium by specific antisera (1 or 10%) significantly reduced IGF-I output. The same effect was observed with an antiserum to progesterone when added at 0.1%, whilst higher doses (1 or 10%) stimulated IGF-I secretion. The present observations demonstrate the involvement of peptide, steroid hormones and cAMP in the regulation of IGF-I secretion by luteinized human granulosa cells. In particular, both GH and oxytocin are stimulators of IGF-I release. Estradiol and androstenedione, but not testosterone, may also be stimulators of IGF-I output. The involvement of progesterone in this process can also not be excluded. A cAMP-dependent intracellular mechanism appears to play an inhibitory role in the regulation of IGF-I secretion by luteinized human granulosa cells.
Schaeffer
H J
HJ
Endokrinologisches Labor, Klinik, Universität zu Köln, Germany.
Sirotkin
A V
AV
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000906:Antibodies / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology*; D004958:Estradiol / Q000276:immunology / Q000502:physiology; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism*; D013006:Growth Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007700:Kinetics; D010121:Oxytocin / Q000494:pharmacology*; D011374:Progesterone / Q000276:immunology / Q000502:physiology; D013256:Steroids / Q000494:pharmacology*
D000906:Antibodies; D013256:Steroids; D005576:Colforsin; D011374:Progesterone; D004958:Estradiol; D010121:Oxytocin; D003994:Bucladesine; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine