Using a spontaneous profile rather than stimulation test makes the KIGS idiopathic growth hormone deficiency model more accessible for clinicians

Duchén, Karel; Lindberg, Anders; Kiplok, Kaire; Kriström, Berit

doi:10.1111/apa.13932

Cited by 8 publications

(8 citation statements)

References 31 publications

(39 reference statements)

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“…Since 1920, when EVANS first demonstrated that the growth-promoting substance in the pituitary gland is growth hormone, scholars have studied the GH gene extensively and intensively, and have achieved important results [35] . It has been reported that growth hormone (GH) is able to combine with the HRE sequence of the β-casein gene to promote receptor activation and synergistically increase the specific expression of lactoproteins [25,36] .…”

Section: Discussionmentioning

confidence: 99%

The High-Level Expression Analysis of RhPA In The RhPA/gGH Double-Transgenic Rabbits And Its Thrombolysis Activity In Vitro

Song

Luo

et al. 2022

Preprint

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Objective: In this study, the rhPA/gGH double transgenic rabbits were constructed, and the expression level of rhPA,rabbit growth and development features were analyzed, which might provide a new idea for obtain rhPA high level expression transgenic animals.Method: Two rhPA transgenic rabbits fertilized eggs were microinjected with linearized GH plasmid to obtain the rhPA/gGH rabbits.The integration of rhPA/gGH gene was detected by PCR. The rhPA expression level in transgenic rabbit milk was detected by ELISA and Western blotting,and FAPA was performed to detect the in vitro thrombolytic activity of rhPA.The body weight of transgenic rabbits at different growth stages were measured to test the effect of gGH gene on rhPA/gGH double transgenic rabbits growth and development .Result: A total of 151 rhPA transgenic rabbits fertilized eggs were obtained through superovulation, 125 of them were microinjected with linearized GH plasmid and transplanted into 8 surrogate mother rabbits.Six surrogate mother rabbits were pregnant, with a pregnancy rate of 75.0% (6/8)，16 rhPA/gGH gene double transgenic rabbits were identified by PCR (10♂,6♀). The rhPA expression levels in rhPA single-transgenic rabbit whey were 0.27–0.63g/L, while the rhPA expression leves were 4.98-12.24 g/L in the rhPA/gGH double-transgenic rabbits whey. The rhPA expression levels of rhPA/gGH double-transgenic rabbit whey were significantly increased by about 17.2–23.8 times, and had higher thrombolytic activity in vitro. There was no significant difference in body weight between rhPA/gGH double transgenic rabbits, rhPA single transgenic or non-transgenic rabbits from birthday to 10 months age(P>0.05). Conclusion: The rhPA/gGH double transgenic rabbits were successfully constrected, which was proved that the introduction of gGH gene could significantly increase the rhPA expression level in the milk of transgenic rabbits and without affecting the growth and development of transgenic rabbits, which laid a foundation for the preparation of transgenic rabbits with higher recombinant protein expression level in the future, and also provide new ideas and new methods for the establishment of mammary gland bioreactor.

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Section: Discussionmentioning

confidence: 99%

The High-Level Expression Analysis of RhPA In The RhPA/gGH Double-Transgenic Rabbits And Its Thrombolysis Activity In Vitro

Song

Luo

et al. 2022

Preprint

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“…IGFBP3 is the main carrier of IGF-1 in blood circulation and can prolong the half-life of IGF-1 in blood circulation. IGF-1 can promote the proliferation of bone cells, increase bone length, participate in the regulation of protein metabolism, induce vitamin D activation (Duchén et al 2017). IGFBP3 plays a role in hypoxia-induced angiogenesis (Granata et al 2007).…”

Section: Discussionmentioning

confidence: 99%

Combination Analysis of NR3C1, MTHFR and IGFBP3 Gene Polymorphisms and DNA Methylation With Steroid-induced Osteonecrosis of the Femoral Head Risk in Chinese Han Population 

Huang¹,

Zhan²,

Hu³

et al. 2020

Preprint

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Background: Although the precise etiology of osteonecrosis of the femoral head (ONFH) has yet to be fully elucidated, it is known that nuclear receptor subfamily3, group C, member 1 (NR3C1), 5, 10-methylenetetrahydrofolate reductase (MTHFR) and insulin-like growth factor-binding protein 3 (IGFBP3) are related to the pathophysiology of steroid-induced osteonecrosis of the femoral head (SONFH). The expression of NR3C1, MTHFR and IGFBP3 are regulated by epigenetics and genetic profiles. Objective: The primary objective of this study was to investigated the association between NR3C1, MTHFR and IGFBP3 gene polymorphisms and DNA methylation status and SONFH.Methods: This case-control study included 79 patients with SONFH and 114 patients who took steroids but did not develop SONFH. We evaluated 5 single-nucleotide polymorphisms (SNPs) out of 3 genes in Chinese Han population. These SNPs were genotyped by improved multiplex ligation detection reaction (iMLDR). Methyltarget was used to test the methylation level of positive sites, the interaction between SNPs and DNA methylation level was analyzed using eQTLD technique.Results: We identified rs3110697 in the IGFBP3 gene that was potentially associated with a reduced risk of SONFH in the genotype (P=0.008; odds ratio [OR]: 0.741; 95% confidence intervals [CI]: 0.456–1.205) and in the recessive model (P=0.003; OR: NA; 95% CI: NA–NA). Furthermore, CpG sites with significant differences in methylation levels were screened as follows: IGFBP3_2-143, MTHFR_1-36, MTHFR_1-77, MTHFR_1-139, MTHFR_2-42, NR3C1_2-163, NR3C1_4-47, and the differences were statistically significant compared with the control group (p<0.05). A total of 10 pairs of linear regression tests of SNP and methylation sites were statistically significant (p<0.05).Conclusions: SONFH is a polygenic disorder in which a wide range of interactions between SNPs and DNA methylation levels may dominate the course of the disease.

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“…All prepubertal children with height below −2 SDS or more than 1.5 SDS below mid‐parental height (MPH) without obvious signs of syndrome were examined with a spontaneous GH profile, 13 and considered for GH treatment based on the prediction according to the model mentioned above.…”

Section: Methodsmentioning

confidence: 99%

A prediction model could foresee adequate height response in children eligible for growth hormone treatment

Fors

Nilsson

et al. 2021

Acta Paediatrica

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Many years of experience with recombinant growth hormone (GH) treatment has shown how effective it is in improving adult height in children with short stature due to GH deficiency (GHD). For those with severe GHD or severe GH insensitivity the diagnosis is often clear, but for a number of short patients it is difficult to draw a clear line between mild GHD, partial GHD and idiopathic short stature. 1 There is consensus that diagnosing GHD in childhood is a multifaceted process requiring both clinical and auxological data, as well as biochemical testing and radiological imaging of skeletal maturity and visualising the pituitary size or possible malformation. 2 However, there is still no gold standard diagnostic test for GHD. The provocation tests available are generally non-physiological and invasive, and are subject to variability between different assays. There is a debate whether measurement of spontaneous GH secretion is

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Using a spontaneous profile rather than stimulation test makes the KIGS idiopathic growth hormone deficiency model more accessible for clinicians

Cited by 8 publications

References 31 publications

The High-Level Expression Analysis of RhPA In The RhPA/gGH Double-Transgenic Rabbits And Its Thrombolysis Activity In Vitro

The High-Level Expression Analysis of RhPA In The RhPA/gGH Double-Transgenic Rabbits And Its Thrombolysis Activity In Vitro

Combination Analysis of NR3C1, MTHFR and IGFBP3 Gene Polymorphisms and DNA Methylation With Steroid-induced Osteonecrosis of the Femoral Head Risk in Chinese Han Population

A prediction model could foresee adequate height response in children eligible for growth hormone treatment

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Using a spontaneous profile rather than stimulation test makes the KIGS idiopathic growth hormone deficiency model more accessible for clinicians

Cited by 8 publications

References 31 publications

The High-Level Expression Analysis of RhPA In The RhPA/gGH Double-Transgenic Rabbits And Its Thrombolysis Activity In Vitro

The High-Level Expression Analysis of RhPA In The RhPA/gGH Double-Transgenic Rabbits And Its Thrombolysis Activity In Vitro

Combination Analysis of NR3C1, MTHFR&nbsp;and IGFBP3&nbsp;Gene Polymorphisms and DNA&nbsp;Methylation With Steroid-induced Osteonecrosis of the Femoral Head Risk in Chinese Han Population&nbsp;

A prediction model could foresee adequate height response in children eligible for growth hormone treatment

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Combination Analysis of NR3C1, MTHFR and IGFBP3 Gene Polymorphisms and DNA Methylation With Steroid-induced Osteonecrosis of the Femoral Head Risk in Chinese Han Population