1.The role of growth hormone in improving oocyte quality in IVF cycles
Maria Jesusa B. Banal-Silao, MD, FPOGS, FPSRM, FPSGE, FPSUOG
Philippine Journal of Reproductive Endocrinology and Infertility 2023;20(1):12-23
Background:
Growth hormone has been used as an adjunct in ovarian stimulation of IVF cycles for the past three decades. However, the exact mechanism of its role in improving oocyte quality has not been thoroughly investigated. Although a clear indication for GH co-treatment is in infertile women with GH deficiency, GH has been given mostly to poor ovarian responders.
Method:
This paper is a review of the most recent published data on the role of GH supplementation in improving oocyte quality in younger women who are suboptimal or unexpected poor responders to standard ovarian stimulation.
Results:
Retrospective cohort and randomized trials demonstrated an improvement in oocyte quality through morphological parameters, mitochondrial function, biomarkers, GH receptors, insulin growth factor, markers of oxidative stress, mature oocytes, good quality embryos, implantation rate, clinical pregnancy and live birth.
Conclusion
Current data suggest GH supplementation may improve oocyte and embryo qualities, endometrial receptivity, clinical pregnancy and live birth. However, better quality evidence is needed before a recommendation can be made for GH supplementation to be given to infertile women who are suboptimal or poor ovarian responders.
growth hormone
;
hormone receptor
;
IGF-1
;
IVF
2.Klotho plays a critical role in clear cell renal cell carcinoma progression and clinical outcome.
Ji Hee KIM ; Kyu Hee HWANG ; Sayamaa LKHAGVADORJ ; Jae Hung JUNG ; Hyun Chul CHUNG ; Kyu Sang PARK ; In Deok KONG ; Minseob EOM ; Seung Kuy CHA
The Korean Journal of Physiology and Pharmacology 2016;20(3):297-304
Klotho functions as a tumor suppressor predominantly expressed in renal tubular cells, the origin of clear cell renal cell carcinoma (ccRCC). Altered expression and/or activity of growth factor receptor have been implicated in ccRCC development. Although Klotho suppresses a tumor progression through growth factor receptor signaling including insulin-like growth factor-1 receptor (IGF-1R), the role of Klotho acting on IGF-1R in ccRCC and its clinical relevance remains obscure. Here, we show that Klotho is favorable prognostic factor for ccRCC and exerts tumor suppressive role for ccRCC through inhibiting IGF-1R signaling. Our data shows the following key findings. First, in tumor tissues, the level of Klotho and IGF-1R expression are low or high, respectively, compared to that of adjacent non-neoplastic parenchyma. Second, the Klotho expression is clearly low in higher grade of ccRCC and is closely associated with clinical outcomes in tumor progression. Third, Klotho suppresses IGF-1-stimulated cell proliferation and migration by inhibiting PI3K/Akt pathway. These results provide compelling evidence supporting that Klotho acting on IGF-1R signaling functions as tumor suppressor in ccRCC and suggest that Klotho is a potential carcinostatis substance for ccRCC.
Carcinoma, Renal Cell*
;
Cell Proliferation
;
Prognosis
;
Receptor, IGF Type 1
3.Dihydromyricetin reverses Herceptin resistance by up-regulating miR-98-5p and inhibiting IGF1R/HER2 dimer formation in SKBR3 cells.
Ming Liang ZHANG ; Chen Xu GUO ; Yun Mian CHU ; Rui XU ; Fa Xiang YIN ; Jun QIAN
Journal of Southern Medical University 2022;42(2):207-214
OBJECTIVE:
To explore the effect of dihydromyricetin on the expression of miR-98-5p and its mechanism in the development of Herceptin resistance in SKBR3 cells.
METHODS:
The expression of IGF2 and miR-98-5p and their interaction relationship were analyzed by bioinformatics analysis through TargetScan online databases. SKBR3 cells and drug-resistant SKBR3-R cells were cultured in cell experiments. Xenograft tumor mice were constructed by SKBR3 and SKBR3-R cells. Proteins were detected by western blotting and immunohistochemistry. Transfected cells were constructed by shRNA lentivirus vectors. RT-QPCR was used to detect RNA. Cell proliferation was detected by MTS method. Cell jnvasion was detected by Transwell assay. Luciferase reporting assays were used to verify RNA interactions. IGF-1R/HER2 heterodimer was determined by immunocoprecipitation.
RESULTS:
The expression of IGF2, p-IGF1R, p-Akt and p-S6K in SKBR3-R cells were significantly higher than those in SKBR3 cells, while the expression of PTEN protein was lower in SKBR3-R cells (P < 0.05). IGF1R/HER2 heterodimer in SKBR3-R cells was significantly increased (P < 0.01).The expression of IGF2 and invasion ability were significantly reduced while transfected with miR-98-5p in SKBR3-R cells (P < 0.05), but the IGF2 mRNA were no difference in both cells (P > 0.05). The expression of miR-98-5p was up-regulated and IGF2 was decreased in drug-resistant xenograft tumor mice after feeding with dihydromyricetin, and the tumor became more sensitivity to Herceptin (P < 0.05).
CONCLUSION
Dihydromyricetin could induce the expression of miR-98-5p, which binds to IGF2 mRNA to reduce IGF2 expression, inhibit the IGF-1R/HER2 formation, thereby reversing cell resistance to Herceptin in SKBR3-R cells.
Animals
;
Cell Line, Tumor
;
Flavonols/pharmacology*
;
Humans
;
Mice
;
MicroRNAs/metabolism*
;
Receptor, IGF Type 1
;
Trastuzumab
4.Correlation between waist circumference and IGF-1 levels in an elderly population in Bali, Indonesia
I Made Pande Dwipayana ; Wira Gotera ; Made Ratna Saraswati ; I Made Siswadi Semadi ; Ida Bagus Aditya Nugraha ; Ketut Suastika ; Anak Agung Gde Budhiarta ; Padma Amrita ; Wahyu Pratama Putra
Journal of the ASEAN Federation of Endocrine Societies 2024;39(2):9-12
Background:
Hyperinsulinemia due to insulin resistance is hypothesized to act as a promotor of cancer growth. In addition to the direct effects of hyperinsulinemia on cancer cells, the stimulation of tumor cell growth can also be indirectly mediated through growth factors and receptors such as insulin-like growth factor 1 (IGF-1). Increased cancer risk is also associated with increased adipose tissue, such as in abdominal obesity, due to the higher risk of insulin resistance and hyperinsulinemia. Waist circumference is a parameter that indicates an individual's level of adiposity. In addition, the risk of cancer also increases in the elderly as they age. This study aims to assess the correlation between waist circumference and IGF-1 levels in the elderly population in Bali, Indonesia.
Methodology:
This study used a cross-sectional analytical design conducted in the Melinggih Village, Gianyar Regency. The study was conducted in September 2023. This study has been approved by the Research Ethics Commission number 2020/UN14.2.2.VII.14/LT/2023. The study population included elderly individuals residing in the Melinggih Village who were willing to participate. Data analysis encompassed descriptive analysis and the Spearman correlation test.
Result:
A total of 88 subjects participated in the study, consisting of 57 females (64.8%) and 31 males (35.2%). A statistically significant but weak correlation coexists between waist circumference and IGF-1 levels.
Conclusion
A weak but statistically significant positive correlation was found between waist circumference and IGF-1 levels in the elderly. However, because of the small sample size, another study with a bigger sample size with enough power to investigate this association needs to be done to validate the results of the current study.
Elderly
;
Aged
;
IGF-1
;
Insulin-Like Growth Factor I
;
Waist Circumference
5.Association between single nucleotide polymorphism of insulin-like growth factor receptor gene and idiopathic short stature.
Hui HUANG ; Yu YANG ; Wei WANG ; Li YANG ; Li-Ling XIE ; Ying WANG ; Hai-Yan WEI
Chinese Journal of Contemporary Pediatrics 2011;13(12):955-958
OBJECTIVETo study the association between single nucleotide polymorphism (SNP) of insulin-like growth factor I receptor (IGF-IR) gene and idiopathic short stature (ISS).
METHODSA total of 804 children with ISS and 575 normal controls were recruited from 2008 to 2011. IGF-IR gene SNP was genotyped using the Snapshot Multiplex System.
RESULTSThe distribution frequency of genotype rs1976667 showed no significant difference between the ISS and the control groups, while that of the allele A of rs1976667 was significantly higher in the ISS group than in the control group (P<0.01).
CONCLUSIONSThe allele A at rs1976667 SNP of IGF-IR gene is a risk factor for ISS.
Adolescent ; Child ; Child, Preschool ; Female ; Growth Disorders ; genetics ; Humans ; Male ; Polymorphism, Single Nucleotide ; Receptor, IGF Type 1 ; genetics
7.A case of acromegaly with mixed papillary-follicular thyroid carcinoma.
Chang Hun LEE ; Nam Il CHEON ; Se In HONG ; Jin Ook CHUNG ; In Seok YOON ; Dong Hyeok CHO ; Ho Cheol KANG ; Dong Jin CHUNG ; Min Young CHUNG
Korean Journal of Medicine 2002;62(3):307-312
Patients with acromegaly have high incidence of benign or malignant neoplasia than general population and many investigators suggest the stimulatory effect of GH and IGF-1 on mesenchymal cells. Both normal thyroid tissue and thyroid cancer cells express IGF-1 receptor and thyroid cancer cells have more than 3 times. We present a case of acromegaly in patient with mixed papillary-follicular thyroid carcinoma, suggesting the possible carcinogenic role of GH and IGF-1.
Acromegaly*
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Humans
;
Incidence
;
Insulin-Like Growth Factor I
;
Receptor, IGF Type 1
;
Research Personnel
;
Thyroid Gland*
;
Thyroid Neoplasms*
8.Mitogenic effects of nicotine to human periodontal ligament(PDL) cells in vitro.
Korean Journal of Orthodontics 1997;27(6):955-961
Nicotine is one of the major components of cigafette smoking which causes various systemic and local diseases to human body. Mitrogenic effects of nicotine to systemic disease are interesting factors in the results of cellular proliferation especially to vascular and pulminary tissus or cells. The study of local effects concerns with destruction of tissue and delayed healing rate after various surgicla treatment. Platelet-Derived Growth factor(PDGF) and Insulin-like growth factor(IGF) are known as major mitogens to human PDL cells. The purpose of this studywas to investgate the mitogenic effects of nicotine to human PDL cells. We studied the expression of PDGF-alpha receptor, PDGF-betareceptor, and IGF-1 receptor mRNA form the nicotine treated human PDL cells by northern analysis. The experimental groups were divided into different serum(1%, 10%) and nicotine(100ng/ml, 1000ng/ml) condentrations and each group was studied by time course. The results of this study showed upregulation of PDGF-alpha, beta receptor and IGF-1 receptor mRNA at 100ng/ml nicotine concentration and 10% serum group to the time course. These results suggest that physiologically attainable nicotine concentrations may stimulate mitogenic gene synthesis to human PDL cells in vitro.
Cell Proliferation
;
Human Body
;
Humans*
;
Mitogens
;
Nicotine*
;
Receptor, IGF Type 1
;
RNA, Messenger
;
Smoke
;
Smoking
;
Up-Regulation
9.A Case of Partial Trisomy 15q25.3-qter.
Ji Hae KIM ; Won Mok LEE ; Nam Hee RYOO ; Jung Sook HA ; Dong Seok JEON ; Jae Ryong KIM ; Joon Sik KIM ; So Young LEE
The Korean Journal of Laboratory Medicine 2009;29(1):66-70
A 15q25-qter partial trisomy characterized by pre or postnatal overgrowth, tall stature, macrocephaly and craniosynostosis has rarely been reported. The cause of overgrowth has been thought to be the triplication of the insulin-like growth factor 1 receptor (IGF1R) gene located on the 15q26.3. We report a patient with partial trisomy 15q25.3-qter showing mental retardation, developmental delay, macrocephaly, long narrow face, ptosis, high palate arch, scoliosis, clinodactyly and overgrowth. Additional material located on terminal 2q was found in karyotyping analysis. In bacterial artificial chromosome (BAC) clone-based-array comparative genomic hybridization (aCGH) analysis, a gain of 31 clones on 15q25.3-qter and a loss of 2 clones on 2q37.3 were observed. An extra copy of IGF1R gene was observed on derivative chromosome 2 in FISH analysis. In conclusion, the patient was diagnosed to have de novo 46,XX,der(2)t(2;15)(q37.3;q25.3) chromosome complement. Adequate genetic counseling and regular follow-ups would be needed for the patient.
Abnormalities, Multiple/genetics
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Child, Preschool
;
*Chromosomes, Human, Pair 15
;
Comparative Genomic Hybridization
;
Female
;
Humans
;
In Situ Hybridization, Fluorescence
;
Karyotyping
;
Receptor, IGF Type 1/*genetics
;
Translocation, Genetic
;
*Trisomy
10.Malignant solitary fibrous tumor of the pleura causing recurrent hypoglycemia; immunohistochemical stain of insulin-like growth factor i receptor in three cases.
Eun Deok CHANG ; Eun Hee LEE ; Yong Soon WON ; Jin Man KIM ; Kwang Sun SUH ; Byung Kee KIM
Journal of Korean Medical Science 2001;16(2):220-224
We present three cases of malignant solitary fibrous tumors of the pleura (SFTP) that produced recurrent hypoglycemia. Removal of the tumors produced normoglycemia. The tumors were well circumscribed and lobulated, and consisted of firm masses weighing 1,150 g to 1,450 g with the greatest diameter of 15 to 20 cm. The tumors were composed of spindle cells in fascicles or in a haphazard arrangement and were highly cellular and mitotically active (3-8 mitoses/10 high-power fields), showing histologically malignant features. Ultrastructurally, fibroblastic features of the tumor cells were present. Insulin-like growth factors (IGF) have been implicated in the presentation of hypoglycemia. The serum insulin and C-peptide levels were not elevated. Serum IGF-I levels were also low with values of 97.4, 157.1 and 51.9 ng/mL (ref. 125-317 ng/mL), respectively. However, tumor cells were strongly positive for IGF-I receptor on immunohistochemical analysis. It is tempting to speculate that IGF-I contributes to the hypoglycemia, even though the circulating levels were low.
Aged
;
Blood Glucose
;
Coin Lesion, Pulmonary/chemistry/*complications/pathology
;
Female
;
Human
;
Hypoglycemia/*etiology
;
Immunohistochemistry
;
Male
;
Middle Age
;
Pleural Neoplasms/chemistry/*complications/pathology
;
Receptor, IGF Type 1/*analysis
;
Recurrence