Insulin-like growth factor binding protein-1 inhibits the DNA amplification induced by insulin-like growth factor I in human granulosa-luteal cells.
In order to study the effects of insulin-like growth factor (IGF-I) and insulin-like growth factor binding protein (IGFBP-1) on human granulosa cell proliferation after in vitro fertilization, cells were obtained after oocyte retrieval and cultured in the presence or absence of graded amounts of recombinant IGF-I, purified IGFBP-1 and [3H]thymidine. Physiological concentrations of IGF-I (2-200 ng/ml) were found to stimulate [3H]thymidine incorporation into the cells in a concentration-dependent manner. Half-maximal stimulation of [3H]thymidine incorporation was obtained with 10 ng/ml exogenous IGF-I, which was chosen for suppression experiments with graded amounts of purified IGFBP-1. Suppression of IGF-stimulated thymidine incorporation was observed when 200 ng/ml or more of IGFBP-1 was added to the culture medium. The same concentration of IGFBP-1 also markedly inhibited binding of [125I]iodotyrosyl IGF-I to the cells. It is concluded that: (i) after a refractory period, granulosa cells from hyperstimulated follicles retained their mitogenic activity; (ii) IGF-I is capable of stimulating DNA amplification in granulosa cells; and (iii) IGFBP-1 inhibits the IGF-I stimulated proliferation in these cells. In view of our previous studies showing that IGFBP-1 is synthesized by the granulosa cells as they luteinize, the present results suggest that IGFBP-1 is one of the endogenous factors locally regulating the growth and differentiation of granulosa cells.
Angervo
M
M
Department I of Obstetrics and Gynecology, Helsinki University Central Hospital, Finland.
Koistinen
R
R
Suikkari
A M
AM
Seppälä
M
M
D002352:Carrier Proteins / Q000502:physiology*; D002478:Cells, Cultured; D003338:Corpus Luteum / Q000166:cytology*; D005260:Female; D005784:Gene Amplification / Q000502:physiology*; D006107:Granulosa Cells / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors*; D007457:Iodine Radioisotopes; D011869:Radioligand Assay
D002352:Carrier Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D007457:Iodine Radioisotopes; D007334:Insulin-Like Growth Factor I