scholarly journals Actions of GnRH antagonists on IGF-II, IGF-binding protein-2 and pregnancy-associated plasma protein-A in human granulosa-lutein cells

2003 ◽  
pp. 31-37 ◽  
Author(s):  
JM Weiss ◽  
B Krautmacher ◽  
S Polack ◽  
K Diedrich ◽  
O Ortmann
Keyword(s):  
Plasma Protein ◽  
Ovarian Function ◽  
Binding Protein ◽  
Protein A ◽  
University Hospital ◽  
Gnrh Antagonists ◽  
Cell Culture Study ◽  
Igf System ◽  
Igf Binding ◽  
Igf Binding Protein

OBJECTIVE: Recently, GnRH antagonists (GnRHants) have been introduced for the prevention of premature LH surges during controlled ovarian hyperstimulation (COH). Here we investigated whether the GnRHants cetrorelix and ganirelix exert effects on the human ovarian IGF system. Since controversy exists on the action of GnRH agonists in the human ovary, we also tested the effect of triptorelin on IGF-II, IGF-binding protein-2 (IGFBP-2) and pregnancy-associated plasma protein-A (PAPP-A) in cultured human granulosa-lutein cells. DESIGN: In vitro cell culture study in a research laboratory of a university hospital. PATIENTS: Cells were obtained from patients treated with different protocols of COH. In addition to gonadotropins they received triptorelin or cetrorelix. Cells were treated with triptorelin, cetrorelix or ganirelix, 1 nmol/l each, for 48 h. IGF-II, IGFBP-2 and PAPP-A were measured by RIA and enzyme immunoassay respectively. RESULTS: GnRHants and triptorelin did not affect IGF-II, IGFBP-2 or PAPP-A. CONCLUSIONS: We conclude that GnRHants do not exert any significant effects on the IGF system of granulosa-lutein cells and therefore their introduction into protocols of COH is unlikely to impair ovarian function.

scholarly journals Insulin-Like Growth Factor Bioactivity, Stanniocalcin-2, Pregnancy-Associated Plasma Protein-A, and IGF-Binding Protein-4 in Pleural Fluid and Serum From Patients With Pulmonary Disease

2017 ◽  
Vol 102 (9) ◽  
pp. 3526-3534 ◽  
Author(s):  
Ulrick Skipper Espelund ◽  
Mette Bjerre ◽  
Rikke Hjortebjerg ◽  
Torben Riis Rasmussen ◽  
Anders Lundby ◽  
...  
Keyword(s):  
Growth Factor ◽  
Pleural Fluid ◽  
Plasma Protein ◽  
Binding Protein ◽  
Protein A ◽  
Insulin Like Growth Factor ◽  
Igf System ◽  
Igf Binding ◽  
Stanniocalcin 2 ◽  
Igf Binding Protein

Abstract Context Members of the insulin-like growth factor (IGF) system are primarily produced in the liver and secreted into the circulation, but they are also produced, recruited, and activated locally in tissues. Objective To compare activity and concentrations of IGF system components in pleural fluid and blood. Design Pathological pleural fluid, secondary to lung cancer or nonmalignant disease, and matching blood samples were collected from 24 patients ages 66.7 to 81.9 years. Methods IGF-related proteins and cytokine levels were measured by immunoassays or immunoblotting. Bioactive IGF was measured by an IGF-1 receptor phosphorylation assay. Results Total IGF-1 concentration did not differ between the compartments, but concentrations of free IGF-1 and bioactive IGF were more than threefold higher in pleural fluid than in corresponding serum samples (P = 0.0004), regardless of etiology. Median pregnancy-associated plasma protein-A (PAPP-A) and interleukin (IL)-6 levels were increased 47-fold and 143-fold, respectively, in pleural fluid compared with plasma (P < 0.0001). PAPP-A and IL-6 concentrations correlated positively (r = 0.46; P = 0.02). In pleural fluid, levels of PAPP-A–generated IGF binding protein-4 fragments correlated inversely with that of stanniocalcin-2 (r ≤ −0.42; P ≤ 0.05), a PAPP-A inhibitor; such correlations were absent in plasma. Conclusion Pathological pleural fluid is characterized by increased in vitro IGF bioactivity and elevated concentrations of PAPP-A, an IGF-activating proteinase. Thus, the tissue activity of the IGF system may differ substantially from that of the circulating IGF system. The correlation between IL-6 and PAPP-A indicates that inflammation plays a role in promoting local tissue IGF activity.

Depot-specific and GH-dependent regulation of IGF binding protein-4, pregnancy-associated plasma protein-A, and stanniocalcin-2 in murine adipose tissue

2018 ◽  
Vol 39 ◽  
pp. 54-61 ◽  
Author(s):  
Rikke Hjortebjerg ◽  
Darlene E. Berryman ◽  
Ross Comisford ◽  
Edward O. List ◽  
Claus Oxvig ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Plasma Protein ◽  
Binding Protein ◽  
Protein A ◽  
Igf Binding ◽  
Stanniocalcin 2 ◽  
Igf Binding Protein

scholarly journals Pregnancy-associated plasma protein A mRNA expression as a marker for differentiated thyroid cancer: results from a “surgical” and a “cytological” series

2021 ◽  
Author(s):  
C. Marzocchi ◽  
M. Capezzone ◽  
A. Sagnella ◽  
A. Cartocci ◽  
M. Caroli Costantini ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Mrna Expression ◽  
Plasma Protein ◽  
Differentiated Thyroid Cancer ◽  
Binding Protein ◽  
Protein A ◽  
Needle Aspiration ◽  
Normal Tissues ◽  
Igf Binding ◽  
Igf Binding Protein

Abstract Purpose Pregnancy-associated plasma protein A (PAPPA) is a metalloproteinase initially described for its role during pregnancy. PAPPA regulates IGF ligands 1 (IGF1) bioavailability through the degradation of IGF-binding protein 4 (IGFBP4). After the cleavage of IGFBP4, free IGF1 is able to bind IGF1 receptors (IGF1R) triggering the downstream signaling. Recently, PAPPA expression has been linked with development of several cancers. No data have been published on thyroid cancer, yet. Methods We evaluated PAPPA, insulin-like growth factor (IGF1), IGF1 receptors (IGF1R) and IGF-binding protein 4 (IGFBP4) mRNA expression levels in a “Surgical series” of 94 thyroid nodules (64 cancers, 16 follicular adenomas and 14 hyperplastic nodules) and in a “Cytological series” of 80 nodules from 74 patients underwent to fine-needle aspiration cytology (FNAC). In tissues, PAPPA was also evaluated by western blot. Results We found that PAPPA expression was increased in thyroid cancer specimen at mRNA and protein levels and that, adenomas and hyperplastic nodules had an expression similar to normal tissues. When applied on thyroid cytologies, PAPPA expression was able to discriminate benign from malignant nodules contributing to pre-surgical classification of the nodules. We calculated a cut-off with a good specificity (91%) which reached 100% when combined with molecular biology. Conclusion These results show that PAPPA could represent a promising diagnostic marker for differentiated thyroid cancer.

IGF dependent modulation of IGF binding protein (IGFBP) proteolysis by pregnancy-associated plasma protein-A (PAPP-A): Multiple PAPP-A–IGFBP interaction sites

2013 ◽  
Vol 1830 (3) ◽  
pp. 2701-2709 ◽  
Author(s):  
Ervinas Gaidamauskas ◽  
Claus Gyrup ◽  
Henning B. Boldt ◽  
Vivien R. Schack ◽  
Michael T. Overgaard ◽  
...  
Keyword(s):  
Plasma Protein ◽  
Binding Protein ◽  
Protein A ◽  
Interaction Sites ◽  
Igf Binding ◽  
Igf Binding Protein

scholarly journals PAPP-A and the IGF system in atherosclerosis: what’s up, what’s down?

2019 ◽  
Vol 317 (5) ◽  
pp. H1039-H1049 ◽  
Author(s):  
Lasse B. Steffensen ◽  
Cheryl A. Conover ◽  
Claus Oxvig
Keyword(s):  
Mouse Models ◽  
Protein A ◽  
Proteolytic Processing ◽  
Igf System ◽  
Mechanistic Insight ◽  
Igf Binding ◽  
Experimental Approaches ◽  
Igf Binding Protein ◽  
Established Role

Pregnancy-associated plasma protein-A (PAPP-A) is a metalloproteinase with a well-established role in releasing bioactive insulin-like growth factor-1 (IGF-1) from IGF-binding protein-2, -4, and -5 by proteolytic processing of these. The IGF system has repeatedly been suggested to be involved in the pathology of atherosclerosis, and both PAPP-A and IGF-1 are proposed biomarkers and therapeutic targets for this disease. Several experimental approaches based on atherosclerosis mouse models have been undertaken to obtain causative and mechanistic insight to the role of these molecules in atherogenesis. However, reports seem conflicting. The literature suggests that PAPP-A is detrimental, while IGF-1 is beneficial. This raises important questions that need to be addressed. Here we summarize the various studies and discuss potential underlying explanations for this seemingly inconsistency with the objective of better understanding complexities and limitations when manipulating the IGF system in mouse models of atherosclerosis. A debate clarifying what’s up and what’s down is highly warranted going forward with the ultimate goal of improving atherosclerosis therapy by targeting the IGF system.

scholarly journals Selection of the Dominant Follicle and Insulin-Like Growth Factor (IGF)-Binding Proteins: Evidence that Pregnancy-Associated Plasma Protein A Contributes to Proteolysis of IGF-Binding Protein 5 in Bovine Follicular Fluid

Endocrinology ◽  
2003 ◽  
Vol 144 (2) ◽  
pp. 437-446 ◽  
Author(s):  
G. M. Rivera ◽  
J. E. Fortune
Keyword(s):  
Proteolytic Activity ◽  
Plasma Protein ◽  
Follicular Fluid ◽  
Binding Proteins ◽  
Protein A ◽  
Positive Control ◽  
Dominant Follicle ◽  
Igf Binding Proteins ◽  
Igf Binding ◽  
Igf Binding Protein

Development of a dominant follicle is associated with decreased intrafollicular low molecular weight IGF-binding proteins (namely IGFBP-2, -4, and -5) and increased proteolysis of IGFBP-4 by pregnancy-associated plasma protein A (PAPP-A). In addition to IGFBP-4 proteolytic activity, bovine follicular fluid contains strong proteolytic activity for IGFBP-5, but not for IGFBP-2. Here we show that the IGFBP-5 protease present in bovine follicular fluid is a neutral/basic pH-favoring, Zn2+ metalloprotease very similar to the previously described IGFBP-4 protease. We hypothesized that immunoneutralization and immunoprecipitation with anti-PAPP-A antibodies would result in abrogation of the IGFBP-4, but not the IGFBP-5, proteolytic activity in follicular fluid. As expected, anti-PAPP-A antibodies were able to neutralize and precipitate the IGFBP-4, but not the IGFBP-5, proteolytic activity of human pregnancy serum, which was used as a positive control for PAPP-A. Surprisingly, immunoneutralization and immunoprecipitation of follicular fluid from bovine preovulatory follicles with anti-PAPP-A antibodies abrogated both IGFBP-4 and IGFBP-5 proteolysis. Quantitative results derived from phosphorimaging revealed a complete inhibition of both IGFBP-4 and -5 proteolysis by follicular fluid incubated for 2 or 5 h in the presence of anti-PAPP-A antibodies. After 18 h of incubation, anti-PAPP-A antibodies still inhibited IGFBP-5 degradation, although with an efficiency lower than that for IGFBP-4 degradation. Both proteolytic activities have identical electrophoretic mobility, and a single band (∼400 kDa) was detected by Western immunoblotting of bovine follicular fluid with anti-PAPP-A antibodies. Proteolysis of IGFBP-5 was readily detectable in follicular fluid from dominant follicles and was negligible in subordinate follicles from the same cohort. These results suggest that an active intrafollicular IGFBP-4/-5 proteolytic system, in which PAPP-A is the major protease involved, is an important determinant of follicular fate.

scholarly journals Concentration of Anti-Müllerian Hormone and Inhibin-B in Relation to Steroids and Age in Follicular Fluid from Small Antral Human Follicles

2008 ◽  
Vol 93 (6) ◽  
pp. 2344-2349 ◽  
Author(s):  
Claus Yding Andersen ◽  
Mikkel Rosendahl ◽  
Anne Grete Byskov
Keyword(s):  
Follicular Fluid ◽  
Malignant Disease ◽  
Binding Protein ◽  
Age Groups ◽  
Significant Negative Correlation ◽  
Inhibin B ◽  
University Hospital ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Prepubertal Girls

Abstract Context: Ovaries surgically removed for fertility preservation served as a source of follicle fluid from human small antral follicles. Objective: The objective of the study was to measure intrafollicular concentrations of anti-Müllerian Hormone (AMH), inhibin-B, progesterone, androstenedione, testosterone, estradiol, and IGF binding protein-4. Setting: The study was conducted at a university hospital. Patients: Patients included 43 women having one ovary removed prior to receiving gonadotoxic treatment due to malignant disease. Interventions: Fluid from 100 follicles (diameter of 3–9 mm) were included. Main Outcome Measures: Intrafollicular concentrations of the measured hormones, their possible intercorrelation, and correlation with age were measured. Results: Concentrations of AMH were unrelated to follicular fluid concentrations of androstenedione and testosterone. There was a significant negative correlation between estradiol, inhibin-B, progesterone, and AMH. In four age groups spanning 11–37 yr, levels of AMH, estradiol, androstenedione, testosterone and inhibin-B remained constant, whereas progesterone showed significant variations. IGF binding protein-4 was unrelated to any other measured hormone. Conclusions: This study was unable to confirm a stimulatory effect of androgens on AMH secretion but did enforce a close intimate correlation between AMH and estradiol expressions in the developing human follicle. The insignificant variation of the AMH concentration with age, even in prepubertal girls, suggests that AMH expression is unrelated to menstrual cycle FSH cyclicity.

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