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Age-associated changes in gene expression in the anterior pituitary glands of female Japanese black cattle


Proper functioning of the anterior pituitary (AP) gland is imperative, however, is suppressed by aging via unclear mechanisms. Therefore, we identified differentially expressed genes (DEGs) in the AP glands of Japanese Black young heifers (approximately 22 months old) compared to old cows (approximately 120 months old) via deep sequencing of the transcriptome (RNA-seq) to characterize potentially important pathways. The young and old AP glands expressed 20,171 annotated genes. Of the total transcripts per million, approximately 41.6% and 35.5% were the sum of seven AP hormone genes in young and old AP glands, respectively, with difference observed in the sum between the young and old AP glands (P < 0.05). Moreover, we identified 48 downregulated genes and 218 upregulated genes in old compared to young AP glands (P < 0.01, fold change > 120%). The DEGs included 1 cytokine (AIMP1), 3 growth factors (NRG2, PTN, and TGFB1), 1 receptor-associated protein gene (AGTRAP), and 10 receptor genes, including PRLHR and two orphan G-protein-coupled receptors (GPR156 and GPR176). Metascape analysis of the DEGs revealed “Peptide metabolic process,” “Regulation of hormone levels,” and “Peptide hormone processing” as enriched pathways. Furthermore, Ingenuity Pathway analysis of the DEGs revealed (1) a network of 24 genes (including GPR156 and PRLHR) named “Neurological disease, organismal injury and abnormalities, and psychological disorders”, and (2) two canonical pathways (P < 0.01), namely “Huntington’s disease signaling”, and “AMPK signaling”. Thus, the findings of the current study revealed relevant DEGs, while identifying important pathways that occur during aging in AP glands of female cattle.

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The datasets of the present study are available from the corresponding authors upon reasonable request.

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DAA and OK were supported by MEXT (Ministry of Education, Culture, Sports, Science, and Technology) with the provision of scholarship.


This research was partly supported by a Grant-in Aid for Scientific Research (JSPS Kakenhi Grant Number 21H02345) from the Japan Society for the Promotion of Science (Tokyo, Japan) to H. Kadokawa.

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DAA contributed to conceptualization, sample collection, and data analysis. OK was involved in conceptualization, sample collection, data analysis, interpreting, and writing the manuscript. YM and KW contributed RNA-seq analyses and data analyses. HK was involved in conceptualization, supervision, methodology, formal analysis, investigation, writing original draft, reviewed the literature, and funding acquisition.

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Correspondence to Hiroya Kadokawa.

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The authors declare no conflicts of interest.

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The study was approved by the Committee on Animal Experiments of Yamaguchi University and complied with relevant legislation (Approval Number, 301).

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Abdillah, D.A., Kereilwe, O., Mizukami, Y. et al. Age-associated changes in gene expression in the anterior pituitary glands of female Japanese black cattle. Mamm Genome (2022).

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