# Transcriptomic regulation of the hypothalamic-pituitary axis by GnRH immunization in Xizang sheep

**Authors:** Tianzeng Song, Shehr Bano Mustafa, Haiyan Li, Xiaoming Zhang, Gaofu Wang, Tingting Zhang, Xiaoying Chen, Jianzhao Cui, Ming Zhang, Xianyin Zeng, Guiqiong Liu, Lili Xian, Zhuoma Jiayang, Wangsheng Zhao, Xunping Jiang

PMC · DOI: 10.1080/10495398.2026.2631819 · Animal Biotechnology · 2026-02-19

## TL;DR

This study explores how GnRH immunization affects the hypothalamic-pituitary axis in Xizang sheep, showing it improves immunity and reduces stress compared to surgical castration.

## Contribution

The study reveals novel transcriptomic mechanisms of GnRH immunization in Xizang sheep, linking immune and neuroendocrine responses.

## Key findings

- GnRH immunization increased serum IgA, IgG, IgM, SOD, and GSH while reducing IL-6 and TNF-α in Xizang sheep.
- Hypothalamic genes like CYTB, ATP6, and COX were upregulated, while SHISA7 and PTPRO were downregulated in the immunization group.
- Pituitary gene RPL15 was upregulated, and genes like RPL10A and CACNA1D were downregulated, with enrichment in muscle and ribosome pathways.

## Abstract

Xizang sheep are vital economic livestock in plateau regions. Traditional surgical castration often induces stress and infection. Although immunization presents an alternative method, the physiological mechanisms underlying its effects in Xizang sheep remain unclear. Therefore, this study integrated serum immune-antioxidant indicators with hypothalamus-pituitary transcriptomics to investigate molecular mechanisms of GnRH immunization. Results indicated that serum IgA, IgG, IgM, SOD, and GSH in the immunization (IM) group were significantly higher than in control (CON) and surgical castration (SN) groups, while IL-6 and TNF-α were significantly reduced (p < 0.05). RNA-seq analysis revealed that hypothalamic CYTB, ATP6, COX, ABLIM1, and ABI3 were significantly upregulated in IM group, whereas SHISA7 and PTPRO were significantly downregulated, with notable enrichment in prion disease, oxidative phosphorylation, and thermogenesis pathways. Pituitary RPL15 was upregulated while RPL10A, CACNA1D, ANK1, DDX3X, and KCNMA1 were significantly downregulated, showing enrichment in myofibril, contractile fiber, sarcomere, and cytosolic ribosome pathways. Association analysis revealed significant positive correlations between IgG and pituitary ATP6, CYTB, TNNI2, as well as hypothalamic COX1, COX, and ND4. In summary, GnRH immunization outperforms surgical castration by modulating hypothalamic-pituitary genes and enhancing immunity and antioxidants in plateau Xizang sheep, achieving integrated neuroendocrine-immune regulation for healthy husbandry of plateau Xizang sheep.

## Linked entities

- **Genes:** CYTB (cytochrome b) [NCBI Gene 4519], ATP6 (ATP synthase F0 subunit 6) [NCBI Gene 4508], COX8A (cytochrome c oxidase subunit 8A) [NCBI Gene 1351], ABLIM1 (actin binding LIM protein 1) [NCBI Gene 3983], ABI3 (ABI family member 3) [NCBI Gene 51225], SHISA7 (shisa family member 7) [NCBI Gene 729956], PTPRO (protein tyrosine phosphatase receptor type O) [NCBI Gene 5800], RPL15 (ribosomal protein L15) [NCBI Gene 6138], RPL10A (ribosomal protein L10a) [NCBI Gene 4736], CACNA1D (calcium voltage-gated channel subunit alpha1 D) [NCBI Gene 776], ANK1 (ankyrin 1) [NCBI Gene 286], DDX3X (DEAD-box helicase 3 X-linked) [NCBI Gene 1654], KCNMA1 (potassium calcium-activated channel subfamily M alpha 1) [NCBI Gene 3778], TNNI2 (troponin I2, fast skeletal type) [NCBI Gene 7136], COX1 (cytochrome c oxidase subunit I) [NCBI Gene 4512], ND4 (NADH dehydrogenase subunit 4) [NCBI Gene 4538]

## Full-text entities

- **Genes:** IL-4 [NCBI Gene 101122781], ND4 [NCBI Gene 808257], SHISA7 [NCBI Gene 101120268], ADPRHL1 [NCBI Gene 101119915], FGF1 [NCBI Gene 101109353], RPL15 [NCBI Gene 101103783], PDYN [NCBI Gene 100294654], MRPL54 [NCBI Gene 101117668], LAPTM4B [NCBI Gene 101107107], PRTG [NCBI Gene 101104497], SLC25A22 [NCBI Gene 101103435], SLC12A5 [NCBI Gene 101114128], EAF1 [NCBI Gene 105610361], ODC1 [NCBI Gene 100192423], GnRH receptor [NCBI Gene 443413], COX2 [NCBI Gene 808252], MIEF1 [NCBI Gene 101107085], SMAD5 [NCBI Gene 443172], IL-2 [NCBI Gene 443401], ND1 [NCBI Gene 808249], PRLH [NCBI Gene 443466], TSHB [NCBI Gene 101104284], Akt [NCBI Gene 100294652], ATP6 [NCBI Gene 808254], IL-6 [NCBI Gene 443406], G protein-coupled receptor [NCBI Gene 443022], GnRH [NCBI Gene 443529], GABRD [NCBI Gene 101122539], NSUN4 [NCBI Gene 101103101], ABLIM1 [NCBI Gene 101102193], FABP3 [NCBI Gene 100913166], LOC442994 [NCBI Gene 442994], KCNMA1 [NCBI Gene 100270685], CRYBB2 [NCBI Gene 101104345], ABI3 [NCBI Gene 101112745], RPL10A [NCBI Gene 106990094], CACNA1D [NCBI Gene 101106371], TNNI2 [NCBI Gene 101121135], COX5A [NCBI Gene 100170667], DDX3X [NCBI Gene 101104719], glucocorticoid receptor [NCBI Gene 443412], MRPL15 [NCBI Gene 101114367], CYTB [NCBI Gene 808260], GH [NCBI Gene 114116958], COX1 [NCBI Gene 808251], VEGFA [NCBI Gene 443103], MRPS16 [NCBI Gene 101118413], TNF-alpha [NCBI Gene 443540], IgA [NCBI Gene 100532871], CGA [NCBI Gene 443538], NDUFA7 [NCBI Gene 101103062], ATP1A3 [NCBI Gene 101103751], ATP5B [NCBI Gene 101106318], ANK1 [NCBI Gene 101121569], PTPRO [NCBI Gene 101104734]
- **Diseases:** infection (MESH:D007239), Amyotrophic lateral sclerosis (MESH:D000690), vesicular transport disorders (MESH:D012872), CRPC (MESH:D064129), Prion disease (MESH:D017096), SCD (MESH:C536778), ND (MESH:C537849), tumor (MESH:D009369), inflammatory (MESH:D007249), prostate cancer (MESH:D011471)
- **Chemicals:** calcium (MESH:D002118), ROS (MESH:D017382), PBS (MESH:D007854), lipid (MESH:D008055), Agarose (MESH:D012685), Specol (MESH:C077974), steroid hormones (MESH:D013256), GSH (MESH:D005978), MDA (MESH:D008315), AOC (-), TRIzol (MESH:C411644), water (MESH:D014867), tricarboxylic acid (MESH:D014233), nitrogen (MESH:D009584), oxygen (MESH:D010100)
- **Species:** Homo sapiens (human, species) [taxon 9606], Sus scrofa (pig, species) [taxon 9823], Ovis aries (domestic sheep, species) [taxon 9940], Mus musculus (house mouse, species) [taxon 10090]

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## Figures

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## References

58 references — full list in the complete paper: https://tomesphere.com/paper/PMC12927403/full.md

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Source: https://tomesphere.com/paper/PMC12927403