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.

Adashi, Eli Y.; Resnick, Carol E.; Ricciarelli, Elisabetta; Hurwitz, Arye; Kokia, Ehud; Tedeschi, Cristina; Botero, Luis; Hernández, Eleuterio R.; Rosenfeld, Ron G.; Carlsson-Skwirut, Christine

doi:10.1172/jci116028

Cited by 49 publications

(20 citation statements)

References 37 publications

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“…The corresponding IGFBP profiles for the two pools of follicular fluid from healthy (lane a) and atretic (lane b) follicles are shown in Figure 3b. In similar experi ments, Adashi et al [33] showed that in vitro, des(l-3)IGF-1 which has a weak affinity for IGFBPs is more potent than IGF-I in promoting the FSH-stimulated accu mulation of progesterone by rat granulosa cells in IGFBP-5-replete circumstances, whereas both peptides are equipotent in IGFBP-5-deplete circumstances.…”

Section: Consequences On the Bioavailability Of Igfs At The Level Of mentioning

confidence: 83%

Insulin-Like Growth Factor-Binding Proteins and Ovarian Folliculogenesis

et al. 1996

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In the ovary, insulin-like growth factors (IGFs) enhance both proliferation and differentiation of follicular cells by potentiating gonadotropin’s actions. The biological effects of IGFs are strikingly modulated by IGF-binding proteins (IGFBPs), whose levels in follicular fluid dramatically change during folliculogenesis. Indeed, in most mammalian species, follicular growth and atresia are characterized by an increase and a great decrease in the IGFBP-3/IGFBPs < 40 kD (IGFBP-2, -4 and -5) ratio in follicular fluid, respectively. These variations result from both changes in expression of these IGFBPs by follicular cells, and in local degradation by specific intrafollicular proteases. Such changes in IGFBP levels lead to great decrease and increase in IGF bioavailability in atretic and growing healthy follicles, respectively. Hence intrafollicular IGFBPs play a key role in the regulation of follicular development by modulating IGFs and therefore gonadotropin’s actions.

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Section: Consequences On the Bioavailability Of Igfs At The Level Of mentioning

confidence: 83%

Insulin-Like Growth Factor-Binding Proteins and Ovarian Folliculogenesis

et al. 1996

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“…IGFBP modulates IGF action in the cell environment, inhibiting or enhancing its activity (17)(18)(19)(20). The inhibitory effects of IGFBP have been attributed to competitive scavenging of IGF peptides from the IGF-1R (42).…”

Section: Discussionmentioning

confidence: 99%

“…MMP-1, MMP-2, and MMP-3 degrade and , and TIMP-1 inhibits proteolytic cleavage of IGFBP-3 in rat pregnant serum (16). IGFBP proteolysis may represent a mechanism for tissue-specific regulation of IGF bioavailability, either inhibiting and/or enhancing IGF activity in many cell types (17)(18)(19)(20).Identification of new hST-3 substrates is a necessary step for the understanding of its physiological relevance. To date, hST-3 proteolytic activity has been described only for the nonspecific MMP substrates ␤-casein and ␣ 2 -macroglobulin.…”

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confidence: 99%

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Identification of Insulin-like Growth Factor-binding Protein-1 as a Potential Physiological Substrate for Human Stromelysin-3

Mañes¹,

Mira²,

Barbacid³

et al. 1997

Journal of Biological Chemistry

190

106

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Proteolysis is central to the regulation of a wide variety of physiological and pathological processes. The matrix metalloproteinases (MMP) 1 constitute an endopeptidase family that includes collagenases, gelatinases, stromelysins, and membrane-type MMP, with a broad spectrum of proteolytic activities toward extracellular matrix (ECM) components (1-3). The proteolytic activity of the matrix metalloproteinases is controlled by their expression as proenzymes that are processed to active forms through proteolysis, as well as by specific physiological tissue inhibitors (TIMP). MMP are believed to mediate many biological processes in which tissue remodeling is implicated, such as embryo implantation and morphogenesis, cell migration, metastasis, tumor invasion, and wound healing (3). Human stromelysin-3 (hST-3, MMP-11) was first described in fibroblasts surrounding neoplastic cells in both primary and metastatic breast tumors, and classified as an MMP on the basis of sequence homology (4). High ST-3 expression has been correlated with increased local tumor aggressiveness (5), and high ST-3 RNA levels are predictive of recurrence in breast carcinoma (6). Recent evidence suggests that hST-3 expression promotes tumor formation in nude mice (7). hST-3 may thus represent a local factor contributing to tumor cell survival and implantation by ECM remodeling. Putative mature forms of hST-3 nevertheless appear unable to degrade any major ECM component (8,9). hST-3 thus may not be considered an ECM degrading enzyme.MMP proteolytic activity on substrates other than matrix components have been reported; shedding activities on tumor necrosis factor-␣ (10, 11), Fas ligand (12), and L-selectin (13) have been ascribed to MMP. Several insulin-like growth factorbinding proteins (IGFBP) have been described as MMP substrates. MMP-1, MMP-2, and MMP-3 degrade and , and TIMP-1 inhibits proteolytic cleavage of IGFBP-3 in rat pregnant serum (16). IGFBP proteolysis may represent a mechanism for tissue-specific regulation of IGF bioavailability, either inhibiting and/or enhancing IGF activity in many cell types (17)(18)(19)(20).Identification of new hST-3 substrates is a necessary step for the understanding of its physiological relevance. To date, hST-3 proteolytic activity has been described only for the nonspecific MMP substrates ␤-casein and ␣ 2 -macroglobulin. When physiologically relevant substrates were sought among tumor cell line-derived secretory products, the unique major hST-3 target molecule was ␣1-protease inhibitor (8). Recent evidence suggests that hST-3 in vivo may contribute to tumor cell survival rather than to tumor invasion (7); this effect on cell viability may thus be mediated by regulating the activity of survival factors such as IGF-I or -II. As a part of a larger study of the relationship between hST-3 and IGF axis on tumor cell proliferation and survival, we tested whether hST-3 might act as an IGFBP-1 protease, thus controlling IGF-I activity at the cellular level.Our data show that (i) IGFBP-1 is a substrate for hS...

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“…The IGFBPs can therefore be considered to play a critical role in modifying the biological actions of IGFs. In the ovary, only inhibitory actions of IGFBPs on follicular function have been demonstrated to date [12][13][14][15][16], Exogenously administered IGFBP-2 and -3 were reported to inhibit FSH-stimulated estradiol and progesterone production in cultured rat granulosa cells [12]. In the rat ovary, the mRNAs for IGFBP-2, IGFBP-3 and IGFBP-4 were shown to be selectively expressed in the interstial cells, copora lutea and granulosa cells of atretic follicles, respectively [17,18].…”

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confidence: 99%