scholarly journals Akt and Erk signal transduction pathways are early markers of differentiation in dominant and subordinate ovarian follicles in cattle

Reproduction ◽  
2007 ◽  
Vol 133 (3) ◽  
pp. 617-626 ◽  
Author(s):  
K E Ryan ◽  
S M Casey ◽  
M J Canty ◽  
M A Crowe ◽  
F Martin ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Signal Transduction Pathways ◽  
Dominant Follicle ◽  
Early Markers ◽  
Igf Binding ◽  
Signal Transduction Proteins ◽  
Igf Binding Protein ◽  
Follicle Selection

Dominant follicles are those that continue to develop and have the potential to ovulate while subordinate follicles regress. Characteristics of dominant follicles include a larger diameter, higher intrafollicular estradiol, and lower IGF-binding protein (IGFBP)-4 concentrations compared with other cohort follicles. Follicle development is regulated by endocrine hormones that act via intracellular signaling pathways. Here, we show the differences in Akt, Erk, c-Jun N-terminal protein kinase, and p-38 signaling pathways between dominant and subordinate follicles at the dominance stage of the follicle wave. However, earlier in the follicle wave (dominant follicle selection), there were only differences in the levels of Akt and Erk signal transduction proteins among dominant and subordinate follicles. Using this profile of Akt and Erk protein expression in granulosa and theca cells of selected dominant follicles compared with subordinate follicles, we suggest a predictive model to identify future dominant and subordinate follicles from the pool of otherwise similar cohort follicles at the time of follicle wave emergence. We conclude that the Erk and Akt signal transduction pathways are important for dominant follicle selection and development and, furthermore, that the observed differences in these pathways mark the future dominant follicle from subordinate follicles before differences in follicular diameter, follicular fluid estradiol, and IGFBP-4 concentrations are apparent.

scholarly journals Follicle selection in cattle and horses: role of intrafollicular factors

Reproduction ◽  
2006 ◽  
Vol 132 (3) ◽  
pp. 365-377 ◽  
Author(s):  
M A Beg ◽  
O J Ginther
Keyword(s):  
The Other ◽  
Dominant Follicle ◽  
Follicular Wave ◽  
Igf System ◽  
Igf I ◽  
The Future ◽  
Igf Binding ◽  
Preparatory Stage ◽  
Igf Binding Protein ◽  
Follicle Selection

The eminent event in follicle selection during a follicular wave in monovular species is diameter deviation, wherein one follicle continues to grow (developing dominant) and other follicles (subordinates) begin to regress. In cattle, the IGF system, oestradiol and LH receptors are involved in the intrafollicular events initiating deviation as indicated by the following: (1) concentrations of free IGF-I and oestradiol in the follicular fluid and number of LH receptors in the follicular wall increase more dramatically in the future dominant follicle than in the future subordinate follicles before the beginning of deviation and (2) ablation of the largest follicle (LF) or injection of recombinant human IGF (rhIGF)-I into the second LF at the expected beginning of deviation increases the concentrations of oestradiol in second LF before the expected beginning of deviation between second LF and third LF. In horses, an increase in free IGF-I, oestradiol, inhibin-A and activin-A is greater in the future dominant follicle than in other follicles before the beginning of deviation. However, free IGF-I is the only one of these four factors needed for the initiation of deviation in horses as indicated by the following: (1) ablation of LF at the expected beginning of deviation increases the concentrations of free IGF-I in second LF before the beginning of deviation between second LF and third LF but does not increase the other factors; (2) injection of rhIGF-I into second LF at the expected beginning of deviation causes second LF to continue to grow and become a codominant follicle and (3) injection of IGF-binding protein-3 into LF at the expected beginning of deviation causes LF to regress and second LF to become dominant. Thus, the dramatic changes in the IGF system in LF compared to other follicles before the beginning of deviation play a crucial role in the events that lead to the beginning of diameter deviation in both cattle and horses. Oestradiol and LH receptors also play a role in cattle. These intrafollicular events prepare the selected follicle for the decreasing availability of FSH and increasing availability of LH. The other follicles of the wave have the same future capability but do not have adequate time to attain a similar preparatory stage.

scholarly journals Interrogation of kinase genetic interactions provides a global view of PAK1-mediated signal transduction pathways

2020 ◽  
Vol 295 (50) ◽  
pp. 16906-16919
Author(s):  
Jae-Hong Kim ◽  
Yeojin Seo ◽  
Myungjin Jo ◽  
Hyejin Jeon ◽  
Young-Seop Kim ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Cell Migration ◽  
Intracellular Signaling ◽  
Mammalian Cells ◽  
Drug Targets ◽  
Large Scale ◽  
Genetic Interaction ◽  
Genetic Interactions ◽  
Signal Transduction Pathways ◽  
Global View

Kinases are critical components of intracellular signaling pathways and have been extensively investigated with regard to their roles in cancer. p21-activated kinase-1 (PAK1) is a serine/threonine kinase that has been previously implicated in numerous biological processes, such as cell migration, cell cycle progression, cell motility, invasion, and angiogenesis, in glioma and other cancers. However, the signaling network linked to PAK1 is not fully defined. We previously reported a large-scale yeast genetic interaction screen using toxicity as a readout to identify candidate PAK1 genetic interactions. En masse transformation of the PAK1 gene into 4,653 homozygous diploid Saccharomyces cerevisiae yeast deletion mutants identified ∼400 candidates that suppressed yeast toxicity. Here we selected 19 candidate PAK1 genetic interactions that had human orthologs and were expressed in glioma for further examination in mammalian cells, brain slice cultures, and orthotopic glioma models. RNAi and pharmacological inhibition of potential PAK1 interactors confirmed that DPP4, KIF11, mTOR, PKM2, SGPP1, TTK, and YWHAE regulate PAK1-induced cell migration and revealed the importance of genes related to the mitotic spindle, proteolysis, autophagy, and metabolism in PAK1-mediated glioma cell migration, drug resistance, and proliferation. AKT1 was further identified as a downstream mediator of the PAK1-TTK genetic interaction. Taken together, these data provide a global view of PAK1-mediated signal transduction pathways and point to potential new drug targets for glioma therapy.

scholarly journals Oxidation Impacts the Intracellular Signaling Machinery in Hematological Disorders

Antioxidants ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 353
Author(s):  
Elena Tibaldi ◽  
Enrica Federti ◽  
Alessandro Matte ◽  
Iana Iatcenko ◽  
Anand B. Wilson ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Conformational Changes ◽  
Intracellular Signaling ◽  
Signal Transduction Pathways ◽  
Functional Connection ◽  
Intracellular Signaling Pathway ◽  
Hematological Disorders ◽  
Dynamic Coordination ◽  
Transduction Mechanisms

The dynamic coordination between kinases and phosphatases is crucial for cell homeostasis, in response to different stresses. The functional connection between oxidation and the intracellular signaling machinery still remains to be investigated. In the last decade, several studies have highlighted the role of reactive oxygen species (ROS) as modulators directly targeting kinases, phosphatases, and downstream modulators, or indirectly acting on cysteine residues on kinases/phosphatases resulting in protein conformational changes with modulation of intracellular signaling pathway(s). Translational studies have revealed the important link between oxidation and signal transduction pathways in hematological disorders. The intricate nature of intracellular signal transduction mechanisms, based on the generation of complex networks of different types of signaling proteins, revealed the novel and important role of phosphatases together with kinases in disease mechanisms. Thus, therapeutic approaches to abnormal signal transduction pathways should consider either inhibition of overactivated/accumulated kinases or homeostatic signaling resetting through the activation of phosphatases. This review discusses the progress in the knowledge of the interplay between oxidation and cell signaling, involving phosphatase/kinase systems in models of globally distributed hematological disorders.

Mutations of Oncogenes Involved in Signal Transduction Pathways Are Common in AML.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2575-2575
Author(s):  
Michael C. Heinrich ◽  
Andrea Haley ◽  
Patina Harell ◽  
Ajia Town ◽  
Troy Bainbridge ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Intracellular Signaling ◽  
Somatic Mutations ◽  
Mapk Pathway ◽  
Direct Sequencing ◽  
Tyrosine Phosphatase ◽  
Signal Transduction Pathways ◽  
Gain Of Function ◽  
Kras Mutations ◽  
Pediatric Leukemia

Abstract AML is the most common type of acute leukemia in adults. Patients typically respond to initial treatment with anthracycline and cytosine arabanoside-based induction chemotherapy, but most patients ultimately relapse and die of refractory disease. Despite advances in supportive care and stem cell transplantation, the overall cure rate in adult AML has not improved significantly in the last decade. The recent success of imatinib mesylate in treating CML has fueled enthusiasm for the further development of AML therapeutic approaches that selectively target aberrant intracellular signaling. To date, inhibition of signaling pathways that are dysregulated by tumor associated somatic mutations have produced the best clinical results. The goal of our study was to more precisely define the frequency and spectrum of mutations affecting receptor tyrosine kinases (FLT3, KIT, PDGFRA, PDGFRB), MAPK pathway (NRAS, KRAS, BRAF), PI3K pathway (PIK3CA), or multiple pathways (PTPN11 tyrosine phosphatase) in adult AML. We analyzed 109 cases of adult AML for genomic DNA abnormalities involving these pathways using a combination of D-HPLC and direct sequencing. In the case of PDGFRA, we performed RT-PCR and FISH to detect FIP1L1-PDGFRA translocations. At least one gain-of-function mutation was found in 53/109 cases (48.6%) (see table) We found mutations of FLT3, KIT, NRAS, KRAS, PTPN11 or BRAF in one or more cases in our series. In contrast, none of the 109 cases had identifiable mutations of PIK3CA, PDGFRA, or PDGFRB. While mutations of NRAS or KRAS were relatively common (19 cases), mutation of BRAF was rare (1/109). In general, mutations of KIT, FLT3, NRAS and KRAS appeared to be mutually exclusive with only 1 AML case having more than one mutation of these genes (1 case with NRAS and KRAS mutations). However, mutations of PTPN11 did not appear to follow this general rule as 5 of the 9 cases with PTPN11 mutations had additional gain-of-function mutation of either FLT3 (3 cases), NRAS (1 case), or both NRAS and KRAS (1 case). We are currently in the process of correlating these mutations with other clinical parameters. We conclude that mutations involving genes directly involved in signal transduction pathways can be found in approximately 50% of cases of adult AML. These mutations represent potential therapeutic targets for treatment with an appropriate small molecular inhibitor. We hypothesize that a more comprehensive kinome wide screen of AML cases would identify an even larger percentage of cases with somatic mutations involving signal transduction pathways. Mutations of PTPN11 have been reported in non-syndromic JMML and rarely in pediatric leukemia. However, the association of PTPN11 mutations in adult AML with mutations of FLT3 or NRAS has not previously been noted. Further studies are required to fully understand the cellular consequences of dysregulated PTPN11 in myeloid leukemogenesis. Our results may also be relevant to ongoing trials of FLT3 or farnesyl transferase inhibitors in AML, as patients with a co-existent PTPN11 mutation may not respond as well to monotherapy with these agents. Mutations of Signal Transduction Pathways in 109 Cases of Adult AML Mutations Number (%) None (wild-type for all genes) 56 (51.4%) FLT3 only 18 (16.5%) FLT3+PTPN11 3 (2.8%) NRAS only 11 (10.1%) NRAS+PTPN11 2 (1.8%) NRAS+KRAS 1 (0.9%) NRAS+KRAS+PTPN11 1 (0.9%) KRAS only 5 (4.6%) KIT only 6 (5.5%) PTPN11 only 4 (3.7%) BRAF only 1 (0.9%)

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 OS5.3 Quantitative signaling pathway analysis of Diffuse Intrinsic Pontine Glioma identifies two subtypes, respectively high TGFβ/MAPK-AP1 and high PI3K/HH pathway activity, which are potentially clinically actionable

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii11-iii11
Author(s):  
A van de Stolpe ◽  
W Verhaegh ◽  
L Holtzer
Keyword(s):  
Signal Transduction ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Pi3k Pathway ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Low Grade Glioma ◽  
Signal Transduction Pathways ◽  
Low Grade ◽  
Pontine Glioma ◽  
Pathway Activity

Abstract BACKGROUND Diffuse Intrinsic Pontine Glioma (DIPG) is a pediatric brain tumor (glioma), resistant to chemotherapy, with only a temporary response to radiotherapy and an extremely bad prognosis. Genomic abnormalities have been found, indicating abnormal activation of certain growth factor signaling pathways, while expression analysis suggests involvement of developmental signaling pathways.10–15 signal transduction pathways can drive cancer growth and metastasis. We have developed, and biologically validated, a method which enables quantitative measurements of functional activity of signal transduction pathways in individual cell/tissue samples, based on Bayesian computational model inference of pathway activity from measurements of mRNA levels of target genes of the transcription factor associated with the respective signalling pathway. A major envisioned clinical utility is prediction of therapy response. MATERIAL AND METHODS For signaling pathway analysis, Affymetrix expression microarray data were available (GEO dataset GSE26576) from 2 normal brain stem samples and from 6 low grade glioma and 26 DIPG samples (post-mortem after therapy). Of one DIPG patient samples were available before and after therapy. Signaling pathway activity scores were calculated for estrogen and androgen receptor, PI3K-FOXO, MAPK-AP1, JAK-STAT, NFκB, Hedgehog (HH), TGFβ, NOTCH and Wnt pathways. PI3K pathway activity is the reverse of FOXO activity, in the absence of oxidative stress (measured by SOD2 expression). Pathway activity scores were compared between normal tissue and low grade glioma samples and DIPG, and k-means cluster analysis was performed on the DIPG pathway activity scores. RESULTS After treatment, HH pathway activity was increased in DIPG compared to low grade glioma (p=0.0003), PI3K pathway activity scores showed large variations in activity in the DIPG group. Tumors with cell cycle (CDK4/6, CCND1-3) or Receptor Tyrosine Kinase-related gene amplifications had higher PI3K and HH pathway activity compared to tumors without identified amplifications (p<0.05) which, in contrast, had higher MAPK-AP1 pathway activity (p<0.002). Pathway-based clustering analysis revealed two DIPG clusters, C1: high TGFβ/MAPK-AP1 and low PI3K/HH pathway activity; C2: low TGFβ/MAPK-AP1, high PI3K/HH pathway activity. C1 best resembled low grade glioma. In the patient with pre/post treatment samples, a C1 pathway profile switched to a C2 profile after treatment. CONCLUSION Using our quantitative analysis of signaling pathway activity in post-treatment DIPG, two pathway activity subtypes were identified, of which the HH/PI3K high, TGFβ low activity subtype was associated with defined gene amplifications, and may have been induced by chemoradiation therapy. Clusters are supported by a clear biological rationale. Identified signaling pathways are potentially drug targetable.

scholarly journals Signal Transduction Due to HIV-1 Envelope Interactions with Chemokine Receptors CXCR4 or CCR5

1997 ◽  
Vol 186 (10) ◽  
pp. 1793-1798 ◽  
Author(s):  
Craig B. Davis ◽  
Ivan Dikic ◽  
Derya Unutmaz ◽  
C. Mark Hill ◽  
James Arthos ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Cell Surface ◽  
Signaling Pathways ◽  
Envelope Glycoprotein ◽  
Intracellular Signaling ◽  
Chemokine Receptors ◽  
Protein Tyrosine Kinase ◽  
Intracellular Signaling Pathways ◽  
Multiple Signaling ◽  
Hiv 1

Infection with HIV-1 requires expression of CD4 and the chemokine receptors CXCR4 or CCR5 at the target cell surface. Engagement of these receptors by the HIV-1 envelope glycoprotein is essential for membrane fusion, but may additionally activate intracellular signaling pathways. In this study, we demonstrate that chemokines and HIV-1 envelope glycoproteins from both T-tropic and macrophage-tropic strains rapidly induce tyrosine phosphorylation of the protein tyrosine kinase Pyk2. The response requires CXCR4 and CCR5 to be accessible on the cell surface. The results presented here provide the first evidence for activation of an intracellular signaling event that can initiate multiple signaling pathways as a consequence of contact between HIV-1 and chemokine receptors.

scholarly journals Insulin-Like Growth Factor (IGF)-I Stimulates Cell Proliferation and Induces IGF Binding Protein (IGFBP)-3 and IGFBP-5 Gene Expression in Cultured Growth Plate Chondrocytes via Distinct Signaling Pathways

Endocrinology ◽  
2005 ◽  
Vol 146 (7) ◽  
pp. 3096-3104 ◽  
Author(s):  
Daniela Kiepe ◽  
Sonia Ciarmatori ◽  
Andreas Hoeflich ◽  
Eckhard Wolf ◽  
Burkhard Tönshoff
Keyword(s):  
Signaling Pathways ◽  
Growth Plate ◽  
Intracellular Signaling ◽  
De Novo ◽  
Growth Plate Chondrocytes ◽  
Intracellular Signaling Pathways ◽  
Igf I ◽  
Rat Growth ◽  
Igf Binding ◽  
Igfbp 3

Abstract The bioactivity of IGF-I in the cellular microenvironment is modulated by both inhibitory and stimulatory IGF binding proteins (IGFBPs), whose production is partially under control of IGF-I. However, little is known on the IGF-mediated regulation of these IGFBPs in the growth plate. We therefore studied the effect of IGF-I on IGFBP synthesis and the involved intracellular signaling pathways in two cell culture models of rat growth plate chondrocytes. In growth plate chondrocytes in primary culture, incubation with IGF-I increased the concentrations of IGFBP-3 and IGFBP-5 in conditioned cell culture medium in a dose- and time-dependent manner. Coincubation of IGF-I with specific inhibitors of the p42/44 MAPK pathway (PD098059 or U0126) completely abolished the stimulatory effect of IGF-I on IGFBP-3 mRNA expression but did not affect increased IGFBP-5 mRNA levels. In contrast, inhibition of the phosphatidylinositol-3 kinase signaling pathway by LY294002 abrogated both IGF-I-stimulated IGFBP-3 and -5 mRNA expression. Comparable results regarding IGFBP-5 were obtained in the mesenchymal chondrogenic cell line RCJ3.1C5.18, which does not express IGFBP-3. The IGF-I-induced IGFBP-5 gene expression required de novo mRNA transcription and de novo protein synthesis. These data suggest that IGF-I modulates its activity in cultured rat growth plate chondrocytes by the synthesis of both inhibitory (IGFBP-3) and stimulatory (IGFBP-5) binding proteins. The finding that IGF-I uses different and only partially overlapping intracellular signaling pathways for the regulation of two IGFBPs with opposing biological functions might be important for the modulation of IGF bioactivity in the cellular microenvironment.

scholarly journals MAPKs in development: insights from Dictyostelium signaling pathways

2011 ◽  
Vol 2 (1-2) ◽  
pp. 39-46 ◽  
Author(s):  
Jeffrey A. Hadwiger ◽  
Hoai-Nghia Nguyen
Keyword(s):  
Signal Transduction ◽  
Signaling Pathways ◽  
Mapk Signaling ◽  
Signal Transduction Pathways ◽  
Signaling Specificity ◽  
Mitogen Activated Protein ◽  
Specific Proteins ◽  
Eukaryotic Organisms ◽  
External Signals ◽  
Multiple Signaling

AbstractMitogen activated protein kinases (MAPKs) play important roles in the development of eukaryotic organisms through the regulation of signal transduction pathways stimulated by external signals. MAPK signaling pathways have been associated with the regulation of cell growth, differentiation, and chemotaxis, indicating that MAPKs contribute to a diverse set of developmental processes. In most eukaryotes, the diversity of external signals is likely to far exceed the diversity of MAPKs, suggesting that multiple signaling pathways might share MAPKs. Do different signaling pathways converge before MAPK function or can MAPKs maintain signaling specificity through interactions with specific proteins? The genetic and biochemical analysis of MAPK pathways in simple eukaryotes such as Dictyostelium offers opportunities to investigate functional specificity of MAPKs in G-protein-mediated signal transduction pathways. This review considers the regulation and specificity of MAPK function in pathways that control Dictyostelium growth and development.

scholarly journals Comparison of mRNA for IGFs and their binding proteins in the oviduct during the peri-oestrous period between dairy heifers and lactating cows

Reproduction ◽  
2011 ◽  
Vol 142 (3) ◽  
pp. 457-465 ◽  
Author(s):  
Theerawat Swangchan-Uthai ◽  
Siobhan W Walsh ◽  
Sarah L H Alexander ◽  
Zhangrui Cheng ◽  
Mark A Crowe ◽  
...  
Keyword(s):  
Dairy Cows ◽  
Early Embryo ◽  
Dominant Follicle ◽  
Embryo Survival ◽  
Lh Surge ◽  
Dairy Heifers ◽  
Lactating Cows ◽  
Holstein Friesian ◽  
Igf Binding ◽  
Igf Binding Protein

The oviduct provides the environment to support gamete maturation, fertilisation and early embryo development. As there is a high incidence of early embryonic death in lactating dairy cows, this study compared expression of IGF family members in the oviduct between lactating Holstein-Friesian dairy cows (n=16, 81±2.4 days in milk) and nulliparous heifers (n=16, age 1.6±0.07 years) at three stages of the oestrous cycle: A) newly selected dominant follicle in the luteal phase, B) follicular phase before the LH surge and C) pre-ovulatory phase after the LH surge. Expression ofIGF1,IGF2, IGF binding protein 2 (IGFBP2),IGFBP3andIGFBP6mRNA was determined in the ampulla of the oviduct. Oviduct side (ipsilateral or contralateral) with respect to the dominant follicle did not affect gene expression. Expression ofIGF1and all threeIGFBPsincreased significantly between the luteal and the pre-ovulatory phases, with no further significant alteration post-LH surge. Concentrations of circulating IGF1 were higher in heifers than in cows, as was the mRNA expression ofIGF1,IGFBP3andIGFBP6. The pre-LH surge rise inIGFBP2mRNA was only observed in heifers.IGF2expression was not influenced by either age or stage of cycle. These three IGFBPs are generally considered to inhibit IGF action. These results indicate tight regulation of IGF bioavailability in the oviductal environment around oestrus, with pronounced differences between cows and heifers, which are likely to influence early embryonic development. Further studies are required to assess the implications for embryo survival.

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