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since 01/2001:

insulin like growth factor 1 OKDB#: 370
 Symbols: IGF1 Species: human
 Synonyms: MGF, IGFI, IGF-I  Locus: 12q23.2 in Homo sapiens

For retrieval of Nucleotide and Amino Acid sequences please go to: OMIM Entrez Gene
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DNA Microarrays
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General Comment

NCBI Summary: The protein encoded by this gene is similar to insulin in function and structure and is a member of a family of proteins involved in mediating growth and development. The encoded protein is processed from a precursor, bound by a specific receptor, and secreted. Defects in this gene are a cause of insulin-like growth factor I deficiency. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar processing to generate mature protein. [provided by RefSeq, Sep 2015]
General function Ligand, Hormone, Growth factor, Extracellular binding protein, Cell death/survival, Anti-apoptotic, DNA Replication, Cell proliferation, Metabolism
Comment Association of In Vitro Fertilization Outcome with Circulating Insulin-like Growth Factor Components Prior to Cycle Initiation. Ramer I et al. (2015) Components of the insulin-like growth factor (IGF) system enhance in vitro embryo quality and implantation rates in both animal models and in human IVF. We evaluated whether differences in serum levels of these components in women prior to initiation of an IVF cycle would be predictive of subsequent outcome. In this retrospective study sera from women obtained at day 2 of their IVF cycle (at baseline before stimulation) were assayed for IGF-I, IGF-II and IGF binding protein (BP)-1 by ELISA. Samples from 54 women with a live birth, 38 with a transient biochemical pregnancy, 45 with a spontaneous abortion, 54 who did not become pregnant and 35 who had an ectopic pregnancy were available for analysis. Associations between the assays and outcome were evaluated by the Kruskall Wallis test and ROC analysis. There were no differences in the number of oocytes retrieved, oocyte quality, fertilization rates, or embryo grade between groups. Median concentrations of IGF-I were elevated in women with a live birth (29.1 ng/ml) as compared to women with a biochemical pregnancy (25.6 ng/ml), spontaneous abortion (21.2 ng/ml), who were not pregnant (18.7 pg/ml) or who had an ectopic pregnancy (4.2 pg/ml) (p <0.001). Conversely, median levels of IGF-II were reduced in women with a live birth (294.5 ng/ml) as opposed to 357.5, 393.6, 407.2 and 426.9ng/ml in women with a biochemical pregnancy, ectopic pregnancy, spontaneous abortion or not pregnant, respectively (p<0.001). Median IGFBP-1 concentrations were markedly elevated in women with a live birth (23.6 ng/ml) compared to 18.3, 14.1, 13.8 and 9.5 ng/ml in women with a biochemical pregnancy, spontaneous abortion, not pregnant or with an ectopic pregnancy (p<0.001). The combination of IGF-I and IGFBP-1 best predicted the occurrence of a live birth with an area under the curve of 0.892. Maternal serum levels of IGF-I, IGF-II and IGFBP-1 prior to initiation of an IVF cycle are correlated with the likelihood of a live birth. Alterations in maternal IGF system components may influence oocyte quality or the success of early post-fertilization events and embryo implantation.////////////////// Dose-response study of intrafollicular injection of insulin-like growth factor-I on follicular fluid factors and follicle dominance in mares. Ginther OJ,et aal . The effect of insulin-like growth factor-I (IGF-I) on the concentrations of follicular fluid factors during follicle deviation and the development of dominance was studied in mares in two experiments. Transvaginal ultrasound guidance was used for intrafollicular injection and subsequent sequential sampling of follicular fluid. Treatment involved a single injection of IGF-I into the second-largest follicle (F2) at the expected beginning of deviation (Hour 0) based on diameter (>/=20 mm) of the largest follicle (F1). Mares in IGF-I groups were given a dose of 500 microg (experiment 1) or 250, 25, or 2.5 microg (experiment 2). Ablation of F1 at Hour 24 was done in experiment 1, but not in experiment 2. The 500- and 250-microg doses stimulated growth, leading to ovulation of F2 in 10 of 10 and 4 of 5 mares in the two experiments, respectively, compared to 4 of 12 and 0 of 5 in saline-injected controls. These doses prevented (P < 0.05) the increase in IGF binding protein-2 and androstenedione that occurred in F2 of controls and increased (P < 0.05) the concentrations of activin-A, inhibin-A, and vascular endothelial growth factor (VEGF). The 500-microg dose stimulated higher (P < 0.05) concentrations of estradiol, but not until Hour 48, whereas the lower doses were ineffective. In experiment 2, free IGF-I concentrations in F2 at Hour 24 decreased progressively as the dose decreased so that concentrations for the 2.5-microg dose were higher (P < 0.05) than in F2 of controls and similar (not significantly different) to endogenous concentrations in F1. Correspondingly, concentrations of androstenedione in F2 at Hour 24 were lower (P < 0.05) and concentrations of activin-A, inhibin-A, and VEGF were higher (P < 0.05) after treatment of F2 with the 2.5-microg dose than in F2 of controls and were similar to concentrations in F1. Hence, a physiologic intrafollicular dose of IGF-I did not stimulate estradiol production but reduced the production of androstenedione and stimulated the production of activin-A, inhibin-A, and VEGF during follicle selection in mares. Oropeza A, et al reported the improvement of the Developmental Capacity of Oocytes from Prepubertal Cattle by Intraovarian Insulin-Like Growth Factor-I Application. The developmental potential of oocytes from prepubertal cattle is decreased compared to those from their adult counterparts. The aim of the present study was to improve the developmental capacity of oocytes from prepubertal cattle by either systemic application of rbST or intraovarian injection of IGF-I. Blastocyst yields and the mRNA expression pattern (relative abundance, RA) of three putative marker genes (i.e. glucose transporter-1, Glut-1; eukaryotic translation initiation factor-1A, eIF1A and upstream binding factor, UBF) were selected as criteria to determine the success of the treatments. At 6-7 months of age, thirty healthy Holstein calves were randomly assigned to three experimental groups. The first group served as control and received an intraovarian injection of 0.6 ml acetic acid. The second group received a single s.c. injection of 500 mg of somatotropin (rbST). The third group received an intraovarian injection of 6 micro g rhIGF-I. During the following two weeks, follicles were aspirated 4 times via transvaginal ultrasound-guided technology. All animals were i.m. injected with 60 mg FSH 48 h prior to each aspiration. The treatments were repeated with the same animals at 9-10, 11-12 and 14-15 months of age. For comparison, five adult cows were i.m. injected each with 100 mg FSH and underwent oocyte retrieval. The proportion of oocytes considered to be developmentally competent was higher in cows than in calves (65% vs. 58%, 50%, 52%) for the control, rbST and IGF-I groups, respectively. The rate of blastocysts was similar in IGF-I treated calves and cows (28% and 25%) and was higher (P
Cellular localization Extracellular Matrix, Secreted
Comment Insulin-like growth factor-1 isoforms in human ovary. Preliminary report on the expression of the IGF-1 gene in PCOS patients and healthy controls. Brazert M et al. (2016) Insulin-like growth factor 1 (IGF-1), produced and secreted locally may affect the mechanisms of folliculogenesis and cause ovarian dysfunction, characteristic of PCOS. The expression of the IGF-1 gene gives rise to three different isoforms of the original molecule. Until now, the role of IGF-1 isoforms has been documented in the repair processes of damaged muscle fibers, cardomyocytes, hepatocytes, and neurons. The literature offers no reports on the presence and role of IGF-1 isoforms in the ovary The aim of the study was to assess the IGF-1A, B and C isoforms at the level of IGF-1 gene transcription in the ovaries of PCOS women and healthy controls. Serum samples and ovarian tissues from PCOS women, treated and non-treated with metformin (PCOS M(+); n = 12 and PCOS M(-), n = 37, respectively), and controls (n = 21) were obtained. The expression of mRNA species of IGF-1 in the ovaries was determined by quantitative RT-PCR. The presence of transcripts of three types of IGF-1 isoforms was observed in healthy controls and PCOS patients, regardless of metformin treatment. Total expression of all isoforms was higher in the M(-)(Me-26640) group as compared to the M(+)(Me- 13470) group, as well as controls (Me-17030)-(not significant, p = 0.061). Similar results for IGF-1A were obtained in all groups. The relative expression of IGF-1A was lower in the M(-)(86.02%) group and differed statistically from controls (91.38%) (p = 0.011). We detected the presence of mRNA for three IGF-1 isoforms in human ovary. To the best of our knowledge, this has been the first report on the presence of mRNA for three IGF-1 isoforms in human ovary. We found differences in the relative expression of IGF-1A isoforms between the investigated groups.////////////////// Insulin-like growth factor 1, liver enzymes, and insulin resistance in patients with PCOS and hirsutism. Çakir E et al. (2014) Hyperinsulinemia and insulin resistance are commonly seen in patients with hirsutism and polycystic ovary syndrome (PCOS), and are associated with cardiovascular disease risk. However, it is not yet known whether insulin-like growth factor I (IGF-I) and alanine transaminase (ALT) produced by the liver play roles in hyperinsulinemia and subclinical atherosclerotic process in patients with PCOS and idiopathic hirsutism (IH). This was a prospective case-controlled study. The study population consisted of 25 reproductive-age PCOS women, 33 women with IH, and 25 control subjects. Mean IGF-I levels and median ALT levels were higher in patients with IH and PCOS than controls, but these differences were not statistically significant. The participants who had a homeostasis model assessment insulin resistance index (HOMA-IR) greater than 2.7 had significantly higher IGF-1 and ALT levels. ALT levels were positively correlated with body mass index, FG, insulin and HOMA-IR. The study illustrated that IGF-1 and ALT levels were significantly higher in patients with increased insulin resistance. Due to short disease duration in younger participants, we did not observe any correlation between IGF-1 and hyperinsulinemia. These findings suggest that increased hepatic production of IGF-I and ALT might be an early indicator of insulin resistance in hirsutism.//////////////////
Ovarian function Follicle development, Initiation of primordial follicle growth, Preantral follicle growth, Antral follicle growth, Follicle atresia, Steroid metabolism, Early embryo development
Comment Insulin-like growth factor-1 (IGF-1) promotes primordial follicle growth and reduces DNA fragmentation through the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signalling pathway. Bezerra MÉS et al. (2018) We investigated the effects of insulin-like growth factor 1 (IGF-1) on the morphology and follicular activation of ovine preantral follicles cultured in situ and whether the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway is involved in IGF-1 action in the sheep ovary. Ovine ovarian fragments were fixed for histological and terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) analyses (fresh control) or cultured in supplemented alpha-minimum essential medium (α-MEM+; control) or α-MEM+ with IGF-1 (1, 10, 50, 100 or 200ngmL-1) for 7 days. Follicles were classified as normal or atretic, primordial or growing and the oocyte and follicle diameters were measured. DNA fragmentation was evaluated by TUNEL assay. Proliferating cell nuclear antigen (PCNA) immunohistochemistry was performed on the fresh control, α-MEM+ and 100ngmL-1 IGF-1 samples. Inhibition of PI3K activity was performed through pretreatment with the PI3K inhibitor LY294002 and phosphorylated AKT (pAKT) expression was analysed after culture in the absence or presence of LY294002. IGF-1 at 100ngmL-1 increased (P<0.05) follicular activation compared with α-MEM+ and decreased TUNEL-positive cells (P<0.05) compared with other treatments. PCNA-positive cells also increased (P<0.05) in 100ngmL-1 IGF-1. LY294002 significantly inhibited follicular activation stimulated by α-MEM+ and 100ngmL-1 IGF-1 and reduced pAKT expression in follicles. Overall, IGF-1 at 100ngmL-1 promoted primordial follicle activation, cell proliferation and reduced DNA fragmentation after in situ culture through the PI3K/AKT pathway.////////////////// Stimulation of the largest subordinate follicle by intrafollicular treatment with insulin-like growth factor 1 is associated with inhibition of the dominant follicle in heifers. Shahiduzzaman AK et al. The effect of intrafollicular treatment of the second-largest follicle (F2) with insulin-like growth factor (IGF) 1 on the largest follicle (F1) and F2 was studied in heifers. Treatment of F2 was done when F1 reached >/=8.2 mm (expected beginning of follicle deviation; Day 0 or Hour 0). In each of two experiments, three groups (n = 6 or 7 heifers/group) were used: controls, F2 treated with vehicle and F2 treated with IGF1. The IGF1 treatment consisted of 200 mug of recombinant human IGF1 (pharmacological dose) in 20 muL of vehicle. In Experiment 1, the hypothesis that treatment of F2 with IGF1 has a stimulatory effect on F2 was supported by a greater (P < 0.05) incidence of F2 dominance (>/=10 mm) in the IGF1 group (71%) than in the other two groups (8%), and a greater (P < 0.02) growth rate of F2 on Days 0-2. Unexpectedly, treatment of F2 with IGF1 had an inhibitory effect on F1, as indicated by a reduced (P < 0.03) growth rate of F1 during Days 0-1 and Days 0-4 and a lesser (P < 0.05) maximum diameter of F1 in the IGF1 group. In Experiment 2, the hypothesis of an inhibitory effect on F1 when F2 was treated with IGF1 was supported by a lesser (P < 0.04) increase in diameter of F1 and a lesser (P < 0.04) percentage of follicle wall with power-Doppler signals of blood flow between Hours 0 and 14 in the IGF1 group. Circulating concentrations of FSH and LH were not altered significantly in either experiment. In conclusion, treatment of F2 with IGF1 at the expected beginning of deviation had a stimulatory effect on F2, but an inhibitory effect on F1. Adashi EY reviewed the literature on IGF system in the ovary. The large body of information now supports the existence of an intraovarian IGF system replete with ligands, receptors, and binding proteins. The intraovarian IGF system is most likely concerned with the amplification of gonadotropin hormonal action, other potential regulatory roles remaining speculative at this time. There is every reason to believe that work in this area in the upcoming several years will yield new insight necessary to establish whether or not IGFs are truly indispensable to ovarian function.Spicer LJ, et al 2000 studied effects of intraovarian infusion of insulin-like growth factor-I on ovarian follicular function in cattle. Fourteen cycling Holstein cows were divided equally into two groups: Control, osmotic minipumps (containing vehicle) surgically inserted into each ovary, or IGF-I treated, osmotic minipumps as in Controls but pumping 2.0 mu g of recombinant human IGF-I per hr for 7 days. Intraovarian IGF-I infusion increased concentrations of IGF-I in follicular fluid of small but not large follicles on Day 7 of treatment. Total ovarian weight (26.4 +/- 2.6 g), and size of the second largest (9.1 +/- 0.2 mm) follicle did not differ (P > 0.10) between control and IGF-I-treated cows. Size of the largest follicle was increased (P < 0.10) in IGF-I-treated versus control cows. IGF-I treatment increased (P < 0.05) estradiol concentrations in follicular fluid of small follicles, but had no effect (P < 0.10) on estradiol concentrations in follicular fluid of large follicles, or on progesterone, androstenedione, or IGF binding protein concentrations in small or large follicles. It was concluded that a 7-day infusion of IGF-I directly into the stroma of the ovary altered follicular growth and follicular fluid estradiol concentrations. Expression of IGFs and their receptors is a potential marker for embryo quality. Liu HC et al. PROBLEM: Insulin-like growth factors (IGFs) and insulin have been demonstrated to stimulate oocyte maturation and embryo development. Therefore, the expression of IGFs and their receptors may be an important intrinsic factor for embryo growth and may be a potential marker for embryo quality. METHOD OF STUDY: Thirty donated day 3 embryos were cultured in vitro for an additional 3 days to observe their developmental potential and were semiquantitatively analyzed for the expression of IGF-I, IGF-II, IGF-IR, IGF-IIR, and insulin-R. RESULTS: Our results show that the activity of these gene expressions correlates well with the morphological assessment and that high and more gene expressions were often associated with embryos of high growth potential. CONCLUSION: The IGF system may indeed play an important role in human embryogenesis; IGF gene expressions can be a good indicator of embryonic developmental stage and/or growth potential; finally, the IGF system can serve as a marker for embryo quality. Effect of IGF-I on pig oocyte maturation, fertilization, and early embryonic development in vitro, and on granulosa and cumulus cell biosynthetic activity. Xia P et al. Porcine granulosa cells have been shown previously to both secrete and respond to insulin-like growth factor-I (IGF-I), suggesting an autocrine function of this peptide in the follicle. The present work was undertaken to determine possible effects of IGF-I on in vitro maturation, in vitro fertilization, and early embryonic development in culture. Granulosa and cumulus cell proliferation and differentiation based on 3H-thymidine uptake and progesterone production, respectively, were also assessed. The results showed that the cleavage rate of oocytes was markedly stimulated in a dose-dependent manner by the addition of IGF-I to the oocyte maturation medium (P < 0.05). Embryo development beyond the 8-cell stage was improved by IGF-I, reaching a maximum of 22% at 200 ng/ml IGF-I. Treatment with IGF-I after fertilization increased the percentage of total oocyte cleavage (P < 0.05) to approximately 52%, 43%, and 57% at, respectively, 25, 50, and 100 ng/ml IGF-I. 3H-thymidine incorporation by granulosa cells was significantly increased in cultures treated with FSH (3-fold) or IGF-I (6-fold) compared to the control. For the cumulus cells, FSH caused a similar increase (3-fold) in 3H-thymidine incorporation while IGF-I stimulated a 15-fold increase. Progesterone production by the granulosa cells was increased to the same extent by treatment with FSH or IGF-I (4.7 and 5.1-fold, respectively). However, for the cumulus cells, while FSH caused a marked 16-fold increase in progesterone production, IGF-I caused only a marginal increase of 2.5-fold.(ABSTRACT TRUNCATED AT 250 WORDS)
Expression regulated by FSH, LH, Steroids, Growth Factors/ cytokines
Ovarian localization Granulosa, Theca, Luteal cells
Follicle stages Secondary, Antral, Preovulatory, Corpus luteum
Phenotypes PCO (polycystic ovarian syndrome)
Mutations 4 mutations

Species: mouse
Mutation name: None
type: null mutation
fertility: subfertile
Comment: Transgenic mice with a homozygous defect of the Igf1 gene (IGF-I knockout mice) have profound embryonic and postnatal growth retardation (Liu et al., 1993 ; [Baker et al., 1993$ 8402902]; [Powell-Braxton et al., 1993 $ 8276243]).

Species: human
Mutation name: None
type: naturally occurring
fertility: unknown
Comment: Woods et al. (1996) described a 15-year-old boy with severe prenatal and postnatal growth failure, sensorineural deafness, and mental retardation who was homozygous for a partial deletion of the IGF1 gene. The patient had been delivered at 37 weeks' gestation by cesarean section because of poor fetal growth. He showed symmetric growth retardation with a birth weight of 1.4 kg, length of 37.8 cm, and head circumference of 27 cm.

Species: human
Mutation name:
type: naturally occurring
fertility: None
Comment: A Microsatellite Polymorphism in IGF1 Gene Promoter and Timing of Natural Menopause in Caucasian Women. Kaczmarek M et al. (2015) Genes involved in the IGF-1 aging pathways in the human ovary can be considered strong candidates for predictors of the natural menopause timing. This study evaluates the association between a cytosine-adenine (CA) microsatellite polymorphism in the IGF1 gene promoter P1 and age at natural menopause. Genomic DNA was extracted from the peripheral blood, PCR was performed using primers designed to amplify the polymorphic (CA) n repeat of the human IGF1 gene, an allele dose effect for the most common (CA)19 repeats allele, Cox proportional hazard regression models and the Kaplan-Meier cumulative survivorship method with the log-rank test were used to determine statistical significance of studied associations in a sample of 257 Polish women aged 40-58 years. Crude Cox proportional hazard regression analysis confirmed the association between the IGF1 gene polymorphism and the menopause timing (p=0.038). This relationship remained statistically significant after controlling for other menopause confounders in multivariate modelling. Out of the input variables, the (CA)n polymorphism in the IGF1 gene promoter, age at menarche and smoking status were independent covariates of the natural menopause timing (χ(2) =12.845; df=3; p=0.034). The onset of menopause at a younger age was likely associated with the IGF1 genotype variant not carrying the (CA)19 repeats allele, menarche before the age of 12 and a current cigarette smoker status (HR=1.6). This study provides evidence that a common cytosine-adenine (CA) microsatellite repeat polymorphism in the P1 promoter region of the IGF1 gene is an independent predictive factor for age at natural menopause in Caucasian women also after adjusting for other menopause covariates.//////////////////

Species: ovine
Mutation name:
type: naturally occurring
fertility: fertile
Comment: Molecular cloning, SNP detection and association analysis of 5' flanking region of the goat IGF1 gene with prolificacy. Thomas N et al. (2016) The insulin-like growth factor 1 has an important role in reproduction, foetal development and growth. It regulates the secretion of gonadotrophin releasing hormone, stimulates ovarian function and steroidogenesis. The present study was conducted to characterise the 5' flanking region of goat IGF1 gene, ascertain ovarian expression of the IGF1gene, detect SNPs and assess the association with prolificacy in the two indigenous goat breeds of South India viz., low prolific Attappady Black and high prolific Malabari. The 5' flanking region of IGF1 gene was PCR amplified, cloned and sequenced from both breeds. Genotyping was performed in 277 goats from the two genetic groups using the PCR-Single Strand Conformational Polymorphism (SSCP) and the expression of the IGF1 gene in the ovary was analysed by quantitative real time PCR. The 5' flanking region of the IGF1 gene was 601bp long and located at 450bp upstream of the start codon. Sequence exhibited 97-99% similarity with that of the sheep, cattle and sika deer IGF1 genes. Three genotypes, PP, PQ and QR were observed at this locus with the frequency of 0.62, 0.30 and 0.08, respectively. Sequencing of the representative PCR products from each genotype revealed two SNPs, g.224A>G and g.227C>T. The population was found to be in Hardy-Weinberg disequilibrium at both loci. Statistical results indicated that these loci were associated with litter size (P≤0.05). However, no significant difference was found in the expression of the IGF1 gene in the ovaries of the two goat breeds. These results suggest the significant influence of the IGF1 gene on prolificacy in goats and identified SNPs would benefit the selection of prolific animals in future breeding programs.//////////////////

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created: Jan. 8, 2000, midnight by: hsueh   email:
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last update: June 6, 2018, 10:22 a.m. by: hsueh    email:

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