Granulosa cell-derived insulin-like growth factor (IGF) binding proteins are inhibitory to IGF-I hormonal action. Evidence derived from the use of a truncated IGF-I analogue.
An increasing body of information now suggests that insulin-like growth factor (IGF) binding proteins (BPs) may serve as antigonadotropins at the level of the ovary. It is the objective of the present communication to evaluate the functional role of endogenous (granulosa cell-derived) IGFBPs by exploiting the unique properties of des(1-3)IGF-I, a naturally occurring IGF-I analogue characterized as a weak ligand of IGFBPs but not of type I IGF receptors. Given IGFBP-replete circumstances, des(1-3)IGF-I proved more potent (10-fold) than its intact counterpart in promoting the follicle stimulating hormone (FSH)-stimulated accumulation of progesterone by cultured rat granulosa cells. In contrast, des(1-3)IGF-I proved virtually equipotent to the unmodified principle under IGFBP-deplete circumstances. Taken together, these findings are in keeping with the notion and that the apparently enhanced potency of des(1-3)IGF-I (under IGFBP-replete conditions) is due to its diminished affinity for endogenously generated IGFBPs and that rat granulosa cell-derived IGFBPs are inhibitory to IGF (and thus inevitably to gonadotropin) hormonal action. Accordingly, the reported ability of gonadotropins to attenuate IGFBP release by granulosa cells may be designed to enhance the bioavailability of endogenously generated IGFs in the best interest of ovarian steroidogenesis.
Adashi
E Y
EY
Department of Obstetrics, Gynecology, and Physiology, University of Maryland School of Medicine, Baltimore 21201.
Resnick
C E
CE
Ricciarelli
E
E
Hurwitz
A
A
Kokia
E
E
Tedeschi
C
C
Botero
L
L
Hernandez
E R
ER
Rosenfeld
R G
RG
Carlsson-Skwirut
C
C
D000818:Animals; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D006107:Granulosa Cells / Q000502:physiology*; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017451:Receptors, Somatomedin / Q000378:metabolism
D002352:Carrier Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D010446:Peptide Fragments; D017451:Receptors, Somatomedin; C058957:insulin-like growth factor 1, des-(1-3)-; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D005640:Follicle Stimulating Hormone