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The Role of Neuropeptides and Their GPCRs in the Neuroendocrine System

A Special Issue of International Journal of Molecular Sciences (ISSN 1422-0067) belonging to the section "Molecular Neurobiology".

Deadline for manuscript submissions: 31 March 2027 | Viewed by 3443

Editor


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Guest Editor
Laboratory of Neuroendocrinology, Department of Biology, Faculty of Environmental, Life, Natural Science and Technology, Okayama University, 3-1-1 Tsushimanaka, Okayama 700-8530, Japan
Interests: neuroendocrinology; neuropeptides; sex steroids; central nervous system; autonomic nervous system; socio-sexual behaviors; sexual dimorphism in the brain; spinal cord; hypothalamus
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Special Issue Information

Dear Colleagues,

The neuroendocrine system controls vital physiological functions, including homeostasis, growth, reproduction, and stress responses, through complex interactions between the nervous and endocrine systems. At the core of this sophisticated regulatory system are diverse neuropeptides and their target G-protein-coupled receptors (GPCRs).

Neuropeptides are secreted by neuroendocrine cells, particularly in the hypothalamus, and participate in a wide range of physiological functions, including pituitary hormone release control, feeding behavior regulation, circadian rhythm maintenance, and emotional control. The actions of these bioactive substances are mediated through specific GPCRs via signal transduction pathways that activate diverse intracellular signaling cascades.

This Special Issue will share the latest research findings and enhance our understanding of neuropeptide–GPCR systems in the neuroendocrine field, from the molecular to organismal level. We aim to offer innovative insights to help advance this field, from basic research to clinical applications.

Prof. Dr. Hirotaka Sakamoto
Guest Editor

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Keywords

  • neuropeptides
  • G-protein-coupled receptors (GPCRs)
  • neuroendocrine system
  • signal transduction
  • hypothalamus

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Published Papers (1 paper)

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Research

13 pages, 1990 KB  
Article
Possible Involvement of Hypothalamic Dysfunction in Long COVID Patients Characterized by Delayed Response to Gonadotropin-Releasing Hormone
by Yuki Otsuka, Yoshiaki Soejima, Yasuhiro Nakano, Atsuhito Suyama, Ryosuke Takase, Kohei Oguni, Yohei Masuda, Daisuke Omura, Yasue Sakurada, Yui Matsuda, Toru Hasegawa, Hiroyuki Honda, Kazuki Tokumasu, Keigo Ueda and Fumio Otsuka
Int. J. Mol. Sci. 2026, 27(2), 832; https://doi.org/10.3390/ijms27020832 - 14 Jan 2026
Cited by 2 | Viewed by 2541
Abstract
Long COVID (LC) may involve endocrine dysfunction; however, the underlying mechanism remains unclear. To examine hypothalamic–pituitary responses in patients with LC, we conducted a single-center retrospective study of patients with refractory LC referred to our University Hospital who underwent anterior pituitary stimulation tests. [...] Read more.
Long COVID (LC) may involve endocrine dysfunction; however, the underlying mechanism remains unclear. To examine hypothalamic–pituitary responses in patients with LC, we conducted a single-center retrospective study of patients with refractory LC referred to our University Hospital who underwent anterior pituitary stimulation tests. Between February 2021 and November 2025, 1251 patients with long COVID were evaluated, of whom 207 (19%) had relatively low random ACTH or cortisol levels. Ultimately, 16 underwent anterior pituitary stimulation tests and were included. All tests were performed in an inpatient setting without exogenous steroids. Fifteen patients (six women, mean age 35.6 years) underwent corticotropin-releasing hormone (CRH), thyrotropin-releasing hormone (TRH), and gonadotropin-releasing hormone (GnRH) tests. All patients had mild acute COVID-19, eight had ≥2 vaccinations, and the mean interval from infection was 343 days. Frequent symptoms included fatigue (100%), insomnia (66.7%), headache (60.0%), anorexia/nausea (40.0%), and brain fog (40.0%). Mean early-morning cortisol and 24 h urinary free cortisol were 7.5 μg/dL and 41.0 μg/day, respectively. MRI showed an empty sella in one case. Peak hormonal responses were preserved (ΔACTH 247%, ΔTSH 918%, ΔPRL 820%, ΔFSH 187%, ΔLH 1150%); however, peaks were delayed beyond 60 min in ACTH (13%), LH (33%), and FSH (87%). Notably, significantly delayed elevations remained at 120 min in the responses of TSH (4.1-fold), PRL (1.8-fold), LH (9.3-fold), and FSH (2.8-fold), suggesting possible hypothalamic involvement, particularly in the gonadotropin responses. Additionally, serum IGF-I was lowered (−0.70 SD), while GH response (mean peak 35.5 ng/mL) was preserved by growth hormone-releasing peptide (GHRP)-2 stimulation. Low-dose hydrocortisone and testosterone were initiated for three patients. Although direct viral effects and secondary suppression have been proposed, our findings may suggest that, at least in part, the observed response characteristics are consistent with functional secondary hypothalamic dysfunction rather than irreversible primary injury. These findings highlight the need for objective endocrine evaluation before initiating hormone replacements. Full article
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