Alterations in Serum miR-126-3p levels over time: a marker of pituitary insufficiency following head trauma

Tufan, Esra, Taheri, Serpil, Karaca, Züleyha, Mehmetbeyoglu, Ecmel, Yilmaz Sukranli, Zeynep, Korkmaz Bayram, Kezban, Ulutabanca, Halil, Tanriverdi, Fatih, Unluhizarci, Kursad, Rassoulzadegan, Minoo and Kelestimur, Fahrettin 2024. Alterations in Serum miR-126-3p levels over time: a marker of pituitary insufficiency following head trauma. Neuroendocrinology 114 (4) , 315–330. 10.1159/000535748

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Abstract

Introduction: Traumatic brain injuries (TBIs) pose a high risk of pituitary insufficiency development in patients. We have previously reported alterations in miR-126-3p levels in sera from patients with TBI-induced pituitary deficiency. Methods: To investigate why TBI-induced pituitary deficiency develops only in some patients and to reveal the relationship between miR-126-3p with hormone axes, we used mice that were epigenetically modified with miR-126-3p at the embryonic stage. These modified mice were subjected to mild TBI (mTBI) according to the Marmarou’s weight-drop model at 2 months of age. The levels of miR-126-3p were assessed at 1 and 30 days in serum after mTBI. Changes in miR-126-3p levels after mTBI of wild-type and miR-126-3p* modified mouse lines validated our human results. Additionally, hypothalamus, pituitary, and adrenal tissues were analyzed for transcripts and associated serum hormone levels. Results: We report that miR-126-3p directly affects hypothalamus-pituitary-adrenal (HPA) axis upregulation and ACTH secretion in the acute phase after mTBI. We also demonstrated that miR-126-3p suppresses Gnrh transcripts in the hypothalamus and pituitary, but this is not reflected in serum FSH/LH levels. The increase in ACTH levels in the acute phase may indicate that upregulation of miR-126-3p at the embryonic stage has a protective effect on the HPA axis after TBI. Notably, the most prominent transcriptional response is found in the adrenals, highlighting their role in the pathophysiology of TBI. Conclusion: Our study revealed the role of miR-126-3p in TBI and pituitary deficiency developing after TBI, and the obtained data will significantly contribute to elucidating the mechanism of pituitary deficiency development after TBI and development of new diagnostic and treatment strategies.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	Karger Publishers
ISSN:	0028-3835
Date of First Compliant Deposit:	15 May 2024
Date of Acceptance:	4 December 2023
Last Modified:	11 Jun 2024 10:01
URI:	https://orca.cardiff.ac.uk/id/eprint/168938

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