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Biomolecules
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Melatonin in Normal Physiology and Disease, 2nd Edition
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Melatonin in Normal Physiology and Disease, 2nd Edition

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 31 December 2025 | Viewed by 3950

Special Issue Editor

Dr. Georges Maestroni

E-Mail Website
Guest Editor
Center of Research in Medical Pharmacology, University of Insubria, 21100 Varese, Italy
Interests: circadian rhythms; melatonin; immune system; adrenergic modulation of hematopoiesis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

Following a very successful first run, we are pleased to announce the launch of a second edition of this Special Issue on “Melatonin in Normal Physiology and Disease”.

In mammals, melatonin is synthesized in virtually all cells of the body, where it functions as an autocrine or paracrine messenger and as a cytoprotective agent by virtue of its detoxifying and antioxidant properties. However, it is the melatonin synthesized in the pineal gland that circulates in the blood in a circadian fashion, playing a vital role in the body. In fact, pineal melatonin transduces light as a basic environmental cue into an endocrine signal capable of synchronizing the entire organism during the photoperiod. As a result, virtually all physiological processes are affected and deranged pineal melatonin production is associated with various pathological states. Melatonin activates two high-affinity membrane receptors, the specific contribution of which to most of its effects is still not clear. This Special Issue aims to gather research articles or reviews on the role of melatonin in normal physiology, including emerging roles such as neurotrophic effects, human reproduction, and mesenchymal stem cell function. In addition, papers on the pathological significance of disturbed melatonin rhythms, as well as the related therapeutic possibilities in inflammatory disorders, skin diseases, viral and bacterial infections, neurodegenerative diseases, cancer, osteoporosis, and autoimmunity, are also welcome.

Dr. Georges Maestroni
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • circadian rhythms
  • immunity
  • skin
  • reproduction
  • aging
  • viral and bacterial infection
  • inflammation
  • mesenchymal stem cells
  • cancer
  • neurodegenerative diseases
  • osteoporosis

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Related Special Issue

Published Papers (4 papers)

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Research

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15 pages, 800 KiB  
Article
Melatonin Secretion and Impacts of Training and Match Schedules on Sleep Quality, Recovery, and Circadian Rhythms in Young Professional Football Players
by Antonio Almendros-Ruiz, Javier Conde-Pipó, Paula Aranda-Martínez, Jesús Olivares-Jabalera, Darío Acuña-Castroviejo, Bernardo Requena, José Fernández-Martínez and Miguel Mariscal-Arcas
Biomolecules 2025, 15(5), 700; https://doi.org/10.3390/biom15050700 - 11 May 2025
Viewed by 1256
Abstract
Modern elite football is becoming increasingly physically demanding, often requiring training and matches to be played at night. This schedule may disrupt circadian rhythms and melatonin secretion, thereby impairing sleep and recovery. This study investigated the effects of training time on melatonin secretion, [...] Read more.
Modern elite football is becoming increasingly physically demanding, often requiring training and matches to be played at night. This schedule may disrupt circadian rhythms and melatonin secretion, thereby impairing sleep and recovery. This study investigated the effects of training time on melatonin secretion, circadian phase markers, and sleep parameters in elite youth soccer players. Forty male players (aged 16–18 years) from an elite Spanish youth football club were studied. Two groups followed the same training program but trained either in the morning (MT) or in the evening (ET). Salivary melatonin was measured at six time points to determine the mean levels, dim light melatonin onset (DLMO), amplitude, and acrophase. Chronotype, sleep quality (PSQI), and daytime sleepiness (ESS) were assessed using validated questionnaires. Dietary intake and anthropometric variables were also recorded. The MT group had higher mean melatonin levels (p = 0.026) and earlier DLMO (p = 0.023) compared to the ET group. Sleep quality was significantly better in the MT group (p < 0.001), despite shorter sleep duration (p = 0.014). No major differences in diet or anthropometry were observed. The chronotype had a secondary effect on the circadian markers. Evening training is associated with alterations in melatonin rhythms and reduced sleep quality, possibly due to light-induced chronodisruption. These findings highlight the importance of training timing as a modifiable factor in the chronobiology and recovery of athletes. Incorporating circadian principles into training schedules may optimize resting time and thus performance and long-term health in athletes. Full article
(This article belongs to the Special Issue Melatonin in Normal Physiology and Disease, 2nd Edition)
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15 pages, 6772 KiB  
Article
Melatonin MT1 Receptor Expression in Luminal Invasive Ductal Breast Carcinoma in Postmenopausal Women
by Leda Pistiolis, Sahar Alawieh, Thorhildur Halldorsdottir, Anikó Kovács and Roger Olofsson Bagge
Biomolecules 2025, 15(4), 581; https://doi.org/10.3390/biom15040581 - 15 Apr 2025
Viewed by 675
Abstract
Laboratory and animal studies indicate that melatonin exerts a negative impact on breast cancer progression and metastasis. These actions are both receptor-dependent and -independent. Of the two transmembrane melatonin receptors identified in humans, breast cancer expresses only MT1. The aim of this study [...] Read more.
Laboratory and animal studies indicate that melatonin exerts a negative impact on breast cancer progression and metastasis. These actions are both receptor-dependent and -independent. Of the two transmembrane melatonin receptors identified in humans, breast cancer expresses only MT1. The aim of this study was to investigate the expression of MT1 in hormone-receptor-positive, HER2-negative invasive ductal breast carcinoma in postmenopausal women and its possible correlations with clinicopathological parameters and survival. A total of 118 patients with luminal A/B primary breast cancer with or without axillary metastases were identified. The MT1 receptor expression was immunohistochemically assessed as a percentage of stained cells and a weighted index (WI) (percentage multiplied by staining intensity). Most tumor samples (84.7%) and metastasized lymph nodes (96%) stained positive for MT1, with varying intensity. No statistically significant correlations were found between the MT1 expression or the WI in the primary tumor and the patient and tumor characteristics, or the MT1 and WI in the metastasized lymph nodes. The survival analysis did not reveal a significant effect of MT1 expression or the WI on the risk of recurrence or survival. Full article
(This article belongs to the Special Issue Melatonin in Normal Physiology and Disease, 2nd Edition)
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Review

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19 pages, 1237 KiB  
Review
Circadian Biomarkers in Humans: Methodological Insights into the Detection of Melatonin and Cortisol
by Cene Skubic, Urša Zevnik, Katarina Nahtigal, Leja Dolenc Grošelj and Damjana Rozman
Biomolecules 2025, 15(7), 1006; https://doi.org/10.3390/biom15071006 - 14 Jul 2025
Viewed by 254
Abstract
Circadian rhythms are intrinsic, with roughly 24 h oscillations that coordinate many physiological functions and are increasingly recognized as key determinants of human health. When these rhythms become misaligned, there is an increased risk for neurodegenerative and psychiatric disorders, metabolic syndrome, sleep disturbances, [...] Read more.
Circadian rhythms are intrinsic, with roughly 24 h oscillations that coordinate many physiological functions and are increasingly recognized as key determinants of human health. When these rhythms become misaligned, there is an increased risk for neurodegenerative and psychiatric disorders, metabolic syndrome, sleep disturbances, and even certain cancers. The hormones, melatonin that rises in the evening and cortisol that peaks shortly after awakening, represent crucial biochemical markers of the circadian phase. This review systematically evaluates contemporary techniques for quantifying melatonin and cortisol, comparing biological matrices (blood, saliva, urine) alongside analytical platforms. Special focus is placed on two clinically informative markers: Dim Light Melatonin Onset (DLMO) and the Cortisol Awakening Response (CAR). We compared immunoassays with liquid chromatography tandem mass spectrometry (LC MS/MS), highlighting differences in sensitivity, specificity, and laboratory feasibility. Potential confounders, including ambient light, body posture, and exact sampling times—are discussed in detail, to show the capacity of providing the most reliable results. By emphasizing the need for standardized protocols and controlled sampling conditions, this review provides essential guidance for researchers and clinicians aiming to assess the circadian biomarkers melatonin and cortisol with precision since they can be used in clinical practice as diagnostic and prognostic tools for assessing numerous pathologies. Full article
(This article belongs to the Special Issue Melatonin in Normal Physiology and Disease, 2nd Edition)
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33 pages, 1114 KiB  
Review
Melatonin Interplay in Physiology and Disease—The Fountain of Eternal Youth Revisited
by Cándido Ortiz-Placín, Ginés María Salido and Antonio González
Biomolecules 2025, 15(5), 682; https://doi.org/10.3390/biom15050682 - 8 May 2025
Viewed by 1174
Abstract
Melatonin (N-acetyl-5-methoxytryptamine) is a hormone associated with the regulation of biological rhythms. The indoleamine is secreted by the pineal gland during the night, following a circadian rhythm. The highest plasmatic levels are reached during the night, whereas the lowest levels are achieved during [...] Read more.
Melatonin (N-acetyl-5-methoxytryptamine) is a hormone associated with the regulation of biological rhythms. The indoleamine is secreted by the pineal gland during the night, following a circadian rhythm. The highest plasmatic levels are reached during the night, whereas the lowest levels are achieved during the day. In addition to the pineal gland, other organs and tissues also produce melatonin, like, for example, the retina, Harderian glands, gut, ovaries, testes, skin, leukocytes, or bone marrow. The list of organs is extensive, including the cerebellum, airway epithelium, liver, kidney, adrenals, thymus, thyroid, pancreas, carotid body, placenta, and endometrium. At all these locations, the availability of melatonin is intended for local use. Interestingly, a decline of the circadian amplitude of the melatonin secretion occurs in old subjects in comparison to that found in younger subjects. Moreover, genetic and environmental factors are the primary causes of diseases, and oxidative stress is a key contributor to most pathologies. Numerous studies exist that show interesting effects of melatonin in different models of disease. Impairment in its secretion might have deleterious consequences for cellular physiology. In this regard, melatonin is a natural compound that is a carrier of a not yet completely known potential that deserves consideration. Thus, melatonin has emerged as a helpful ally that could be considered as a guard with powerful tools to orchestrate homeostasis in the body, majorly based on its antioxidant effects. In this review, we provide an overview of the widespread actions of melatonin against diseases preferentially affecting the elderly. Full article
(This article belongs to the Special Issue Melatonin in Normal Physiology and Disease, 2nd Edition)
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