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Innate differences in the molecular signature of normal inferior & superior human parathyroid glands: potential implications for parathyroid adenoma

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Abstract

Primary hyperparathyroidism is a common endocrine disorder. Interestingly, the majority (75%) of parathyroid tumors are localized to the inferior parathyroid glands. To date, the reason for this natural bias has not been investigated. We assessed the global gene expression profile of superior and inferior glands obtained from forensic autopsies. The genes with significant differential expression between superior and inferior parathyroids were further assessed by RT-PCR in 19 pairs. As an iterative approach, additional genes with an established role in parathyroid disorders, i.e., CASR, MAFB, PAX9, TBCE, TBX1, VDR, MEN1, CCND1, and CDC73 were also evaluated by RT-PCR in all 19 pairs of superior and inferior parathyroid glands. Seven homeobox genes, namely HOXA4, HOXA5, HOXBAS3, HOXB4, HOXB6, HOXB9, IRX1, and one encoding for ALDH1A2 showed a lower expression in the inferior parathyroid glands than in the superior. Conversely, SLC6A1 showed a higher expression in the inferior glands. Of the nine genes with significant differential mRNA expression among superior and inferior glands HOXB9, HOXB4 and IRX1 could be detected by western blotting/mass spectrometry. The study is the first to show the differential expression of nine genes HOXA4, HOXA5, HOXBAS3, HOXB4, HOXB6, HOXB9, IRX1, ALDH1A2, and SLC6A1 in inferior versus the superior parathyroid glands. This could have potential implications for the preferential localization of parathyroid tumors to the inferior parathyroid glands as observed in patients with primary hyperparathyroidism.

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Data availability

Some or all datasets generated during and/or analyzed during the current study are not publicly available but are available from the corresponding author upon reasonable request.

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Funding

This work was supported by the All India Institute of Medical Sciences, New Delhi (intramural Grant Number A-694).

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Authors and Affiliations

  1. Department of Pathology, All India Institute of Medical Sciences, New Delhi, India

    Shipra Agarwal & Monikongkona Boruah

  2. Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, India

    Parmita Kar & Soma Saha

  3. Department of Forensic Medicine and Toxicology, All India Institute of Medical Sciences, New Delhi, India

    Tabin Millo

  4. Department of Surgical Oncology, All India Institute of Medical Sciences, New Delhi, India

    Chitresh Kumar

  5. Department of Surgery, All India Institute of Medical Sciences, New Delhi, India

    Seenu Vuthaluru

  6. Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, 110029, India

    Ravinder Goswami

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  1. Shipra Agarwal
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  2. Parmita Kar
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  4. Soma Saha
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  8. Ravinder Goswami
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Contributions

The study was designed by RG, SA; TM, CK, VS, MB, and SA, who were involved in procuring the autopsy tissues. SA, PK, MB, and SS carried out the experiments; SA helped with histopathological evaluation of the collected autopsy tissues; RG, SA, PK, and SS contributed to data analysis. All the authors contributed to the writing of the manuscript.

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Correspondence to Ravinder Goswami.

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Agarwal, S., Kar, P., Boruah, M. et al. Innate differences in the molecular signature of normal inferior & superior human parathyroid glands: potential implications for parathyroid adenoma. Mol Cell Biochem 478, 2351–2359 (2023). https://doi.org/10.1007/s11010-023-04664-9

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  • DOI: https://doi.org/10.1007/s11010-023-04664-9

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