Adropin, a novel hepatokine: localization and expression during postnatal development and its impact on testicular functions of pre-pubertal mice
- PMID: 38087073
- DOI: 10.1007/s00441-023-03852-9
Adropin, a novel hepatokine: localization and expression during postnatal development and its impact on testicular functions of pre-pubertal mice
Abstract
Adropin, a multifaceted peptide, was identified as a new metabolic hormone responsible for regulating gluco-lipid homeostasis. However, its role in the testicular function is not yet understood. We aimed to investigate the localization and expression of adropin and GPR19 during different phases of postnatal development. Immunohistochemical study revealed the intense reactivity of adropin in the Leydig cells during all phases of postnatal development, while GPR19 showed intense immunoreactivity in the pachytene spermatocytes and mild immunoreactivity in Leydig cells as well as primary and secondary spermatocytes. Western blot study revealed maximum expression of GPR19 in pre-pubertal mouse testis that clearly indicates maximum responsiveness of adropin during that period. So, we hypothesized that adropin may act as an autocrine/paracrine factor that regulates pubertal changes in mouse testis. To examine the effect of adropin on pubertal onset, we gave bilateral intra-testicular doses (0.5 and 1.5 µg/testis) to pre-pubertal mice. Adropin treatment promoted testicular testosterone synthesis by increasing the expression of StAR, 3β-HSD, and 17β-HSD. Adropin also promoted germ cell survival and proliferation by upregulating the expression of PCNA and downregulating the Bax/Bcl2 ratio and Caspase 3 expression resulting in fewer TUNEL-positive cells in adropin-treated groups. FACS analysis demonstrated that adropin treatment not only increases 1C to 4C ratio but also significantly increases the 1C (spermatid) and 1C to 2C ratio which demarcates accelerated germ cell differentiation and turnover of testicular cells. In conclusion, adropin promotes steroidogenesis, germ cell survival, as well as the proliferation in the pre-pubertal mouse testis that may hasten the pubertal transition in an autocrine/paracrine manner.
Keywords: Adropin; GPR19; Puberty; Steroidogenesis; Testes.
© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
References
-
- Alexander SPH, Battey J, Benson HE, Benya RV, Bonner TI, Davenport AP, Dhanachandra Singh, K Eguchi S, Harmar A, Holliday N, Jensen RT, Karnik S, Kostenis E, Liew WC, Monaghan AE, Mpamhanga C, Neubig R, Pawson AJ, Pin JP, Vanderheyden P (2021) Class A orphans in GtoPdb v.2021.3. IUPHAR/BPS Guide to pharmacology CITE, 2021(3). https://doi.org/10.2218/gtopdb/F16/2021.3
-
- Alotaibi MF (2019) Physiology of puberty in boys and girls and pathological disorders affecting its onset. J Adolesc 71:63–71. https://doi.org/10.1016/j.adolescence.2018.12.007 - DOI - PubMed
-
- Beau C, Vivian N, Münsterberg A, Dresser DW, Lovell-Badge R, Guerrier D (2001) In vivo analysis of the regulation of the anti-Müllerian hormone, as a marker of Sertoli cell differentiation during testicular development, reveals a multi-step process. Mol Reprod Dev 59(3):256–264. https://doi.org/10.1002/mrd.1030 - DOI - PubMed
-
- Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72(1–2):248–254. https://doi.org/10.1016/0003-2697(76)90527-3 - DOI - PubMed
-
- Butler AA, Havel PJ (2021) Adropin and insulin resistance: Integration of endocrine, circadian, and stress signals regulating glucose metabolism. Obesity 29(11):1799–1801. https://doi.org/10.1002/oby.23249 - DOI - PubMed
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Research Materials
Miscellaneous
