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Expression of polyamines and its association with GnRH-I in the hypothalamus during aging in rodent model

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Abstract

GnRH-I and GnIH are the key neuropeptides that regulate the hypothalamic–pituitary–gonadal axis in mammals during aging. Polyamines are important aliphatic amines that are expressed in the brain and show variation with aging. The present study demonstrates evidence of variation in the level of expression of polyamines, GnRH-I and GnIH in the hypothalamus of female mice during aging. The study also suggests regulatory effects of polyamines over expression of the hypothalamic GnRH-I. The study shows a significant positive correlation between polyamines, its associated factors and GnRH-I along with significant negative correlation between polyamines, its associated factors and GnIH. This is the first study to report the effect of polyamines along with lactate or TNF-α or both on GnRH-I expression in GT1-7 cell line. TNF-α and lactate significantly decreased hypothalamic GnRH-I mRNA expression in GT1-7 cells when treated for 24 h. Polyamines (putrescine and agmatine) in contrast, significantly increased GnRH-I mRNA expression in GT1-7 cells when treated for 24 h. Also, polyamines increased GnRH-I mRNA expression when treated in presence of TNF-α or lactate thereby suggesting its neuro-protective role. This study also found 3809 differentially expressed genes through RNA-seq done between the hypothalamic GT1-7 cells treated with putrescine only versus TNF-α and putrescine. The present study suggests for the first time that putrescine treatment to TNFα-primed GT1-7 cells upregulates GnRH-I expression via regulation of several pathways such as calcium ion pathway, estrogen signaling, clock genes as well as regulating other metabolic process like neuronal differentiation and neurulation.

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Acknowledgements

Work was supported by Science and Engineering Research Board (EMR/2017/004290) and Department of Biotechnology, Ministry of Science and Technology (BT/PR32910/MED/97/473/2020), New Delhi, India, financial assistance provided to Dr. Arnab Banerjee. SERB-NPDF (PDF/2017/000989) Moitreyi Das. Financial assistance from UGC-CSIR JRF provided to Nayan Anand Mate. We also thank Dr. G. Karthikeyan, BITS Pilani KK Birla Goa Campus, Goa, India, for providing the microscope facility. And we thank Dr Kazuyoshi Tsutsui Laboratory of Integrative Brain Sciences, Department of Biology, Center for Medical Life Science of Waseda University, Waseda University, Tokyo, Japan for the generous gift of GnIH antibody.

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Authors and Affiliations

  1. Department of Biological Sciences, KK Birla, Goa Campus, BITS Pilani, Zuarinagar, Goa, India

    Nayan Mate, Rohit Shaji & Arnab Banerjee

  2. Department of Zoology, Goa University, Goa, India

    Moitreyi Das

  3. Department of Mathematics, KK Birla, Goa Campus, BITS Pilani, Zuarinagar, Goa, India

    Sammit Jain

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  1. Nayan Mate
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Contributions

Dr. AB conceived and designed the study, drafted and approved of the manuscript. NAM designed and performed major experiments and analyzed the data. MD conducted some experiments. NAM and Dr. AB wrote the first draft of the manuscript. SJ carried out the quantification of protein expression by the metric of relative pixel count method. RS analyzed RNA seq data and also contributed in writing the manuscript. All authors read, edited, reassessed the studies and contributed to the final manuscript.

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Correspondence to Arnab Banerjee.

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Mate, N., Shaji, R., Das, M. et al. Expression of polyamines and its association with GnRH-I in the hypothalamus during aging in rodent model. Amino Acids 54, 1135–1154 (2022). https://doi.org/10.1007/s00726-022-03139-3

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