- Adrenal Gland
- Clinical and Molecular Characteristics of PRKACA L206R Mutant Cortisol-Producing Adenomas in Korean Patients
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Insoon Jang, Su-jin Kim, Ra-Young Song, Kwangsoo Kim, Seongmin Choi, Jang-Seok Lee, Min-Kyeong Gwon, Moon Woo Seong, Kyu Eun Lee, Jung Hee Kim
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Endocrinol Metab. 2021;36(6):1287-1297. Published online December 2, 2021
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DOI: https://doi.org/10.3803/EnM.2021.1217
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 Abstract
 PDF Supplementary Material PubReader  ePub
- Background
An activating mutation (c.617A>C/p.Lys206Arg, L206R) in protein kinase cAMP-activated catalytic subunit alpha (PRKACA) has been reported in 35% to 65% of cases of cortisol-producing adenomas (CPAs). We aimed to compare the clinical characteristics and transcriptome analysis between PRKACA L206R mutants and wild-type CPAs in Korea.
Methods
We included 57 subjects with CPAs who underwent adrenalectomy at Seoul National University Hospital. Sanger sequencing for PRKACA was conducted in 57 CPA tumor tissues. RNA sequencing was performed in 13 fresh-frozen tumor tissues.
Results
The prevalence of the PRKACA L206R mutation was 51% (29/57). The mean age of the study subjects was 42±12 years, and 87.7% (50/57) of the patients were female. Subjects with PRKACA L206R mutant CPAs showed smaller adenoma size (3.3±0.7 cm vs. 3.8±1.2 cm, P=0.059) and lower dehydroepiandrosterone sulfate levels (218±180 ng/mL vs. 1,511±3,307 ng/mL, P=0.001) than those with PRKACA wild-type CPAs. Transcriptome profiling identified 244 differentially expressed genes (DEGs) between PRKACA L206R mutant (n=8) and wild-type CPAs (n=5), including five upregulated and 239 downregulated genes in PRKACA L206R mutant CPAs (|fold change| ≥2, P<0.05). Among the upstream regulators of DEGs, CTNNB1 was the most significant transcription regulator. In several pathway analyses, the Wnt signaling pathway was downregulated and the steroid biosynthesis pathway was upregulated in PRKACA mutants. Protein-protein interaction analysis also showed that PRKACA downregulates Wnt signaling and upregulates steroid biosynthesis.
Conclusion
The PRKACA L206R mutation in CPAs causes high hormonal activity with a limited proliferative capacity, as supported by transcriptome profiling.
- Endocrine Research
- Transformation of Mature Osteoblasts into Bone Lining Cells and RNA Sequencing-Based Transcriptome Profiling of Mouse Bone during Mechanical Unloading
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A Ram Hong, Kwangsoo Kim, Ji Yeon Lee, Jae-Yeon Yang, Jung Hee Kim, Chan Soo Shin, Sang Wan Kim
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Endocrinol Metab. 2020;35(2):456-469. Published online June 24, 2020
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DOI: https://doi.org/10.3803/EnM.2020.35.2.456
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Correction in: Endocrinol Metab 2021;36(6):1314
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Abstract
PDFSupplementary MaterialPubReader ePub
- Background
We investigated RNA sequencing-based transcriptome profiling and the transformation of mature osteoblasts into bone lining cells (BLCs) through a lineage tracing study to better understand the effect of mechanical unloading on bone loss.
Methods
Dmp1-CreERt2(+):Rosa26R mice were injected with 1 mg of 4-hydroxy-tamoxifen three times a week starting at postnatal week 7, and subjected to a combination of botulinum toxin injection with left hindlimb tenotomy starting at postnatal week 8 to 10. The animals were euthanized at postnatal weeks 8, 9, 10, and 12. We quantified the number and thickness of X-gal(+) cells on the periosteum of the right and left femoral bones at each time point.
Results
Two weeks after unloading, a significant decrease in the number and a subtle change in the thickness of X-gal(+) cells were observed in the left hindlimbs compared with the right hindlimbs. At 4 weeks after unloading, the decrease in the thickness was accelerated in the left hindlimbs, although the number of labeled cells was comparable. RNA sequencing analysis showed downregulation of 315 genes in the left hindlimbs at 2 and 4 weeks after unloading. Of these, Xirp2, AMPD1, Mettl11b, NEXN, CYP2E1, Bche, Ppp1r3c, Tceal7, and Gadl1 were upregulated during osteoblastogenic/osteocytic and myogenic differentiation in vitro.
Conclusion
These findings demonstrate that mechanical unloading can accelerate the transformation of mature osteoblasts into BLCs in the early stages of bone loss in vivo. Furthermore, some of the genes involved in this process may have a pleiotropic effect on both bone and muscle.
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Citations
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