Maternal melatonin selectively inhibits cortisol production in the primate fetal adrenal gland
Open accessAbstract
We tested the hypothesis that in primates, maternal melatonin restrains fetal and newborn adrenal cortisol production. A functional G‐protein‐coupled MT1 membrane‐bound melatonin receptor was detected in 90% gestation capuchin monkey fetal adrenals by (a) 2‐[125 I] iodomelatonin binding (Kd, 75.7 ± 6.9 p m; Bmax, 2.6 ± 0.4 fmol (mg protein)−1), (b) cDNA identification, and (c) melatonin inhibition of adrenocorticotrophic hormone (ACTH)‐ and corticotrophin‐releasing hormone (CRH)‐stimulated cortisol but not of dehydroepiandrosterone sulphate (DHAS) production in vitro. Melatonin also inhibited ACTH‐induced 3β‐hydroxysteroid dehydrogenase mRNA expression. To assess the physiological relevance of these findings, we next studied the effect of chronic maternal melatonin suppression (induced by exposure to constant light during the last third of gestation) on maternal plasma oestradiol during gestation and on plasma cortisol concentration in the 4‐ to 6‐day‐old newborn. Constant light suppressed maternal melatonin without affecting maternal plasma oestradiol concentration, consistent with no effect on fetal DHAS, the precursor of maternal oestradiol. However, newborns from mothers under constant light condition had twice as much plasma cortisol as newborns from mothers maintained under a normal light–dark schedule. Newborns from mothers exposed to chronic constant light and daily melatonin replacement had normal plasma cortisol concentration. Our results support a role of maternal melatonin in fetal and neonatal primate cortisol regulation.
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Exposing pregnant non-human primates to constant light suppresses the emergence of melatonin and body temperature rhythms in their offspring following birth, suggesting that maternal rhythms are important for the early brain development of fetal circadian systems.
“Exposing pregnant NHPs to constant light suppresses the emergence of melatonin and body temperature rhythms in their offspring following birth42–44, suggesting that maternal rhythms are important for the early brain development of fetal circadian systems45.”
From Rhythms of life: circadian disruption and brain disorders across the lifespan (2019) · cites this paper as [42]
Perturbed maternal melatonin signaling is a proposed mechanism by which circadian disruption negatively impacts development.
“Previous studies have proposed that perturbed maternal melatonin signaling is a mechanism by which circadian disruption negatively impacts development15, 17, 20–25.”
From Maternal and Early-Life Circadian Disruption Have Long-Lasting Negative Consequences on Offspring Development and Adult Behavior in Mice (2017) · cites this paper as [17]
Maternal circadian disruption alters offspring metabolic functioning in adulthood, including regulation of glucocorticoids and insulin.
“Likewise, maternal circadian disruption alters offspring metabolic functioning in adulthood13, 17–19, including the regulation of glucocorticoids17 and insulin18.”
From Maternal and Early-Life Circadian Disruption Have Long-Lasting Negative Consequences on Offspring Development and Adult Behavior in Mice (2017) · cites this paper as [17]
Developing offspring rely on metabolic and hormonal information communicated from mother to fetuses.
“and developing offspring rely on metabolic and hormonal information communicated from mother to fetuses17, 20, 58.”
From Maternal and Early-Life Circadian Disruption Have Long-Lasting Negative Consequences on Offspring Development and Adult Behavior in Mice (2017) · cites this paper as [17]
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- Authors
- Torres‐Farfan, C., Richter, H. G., Germain, A. M., Valenzuela, G. J., Campino, C., Rojas‐García, P., Forcelledo, M. L., Torrealba, F., & Serón‐Ferré, M.
- Affiliations
- Pontificia Universidad Católica de Chile (CL)
- Arrowhead Regional Medical Center (US)
- ORCID
- Venue
- The Journal of Physiology
- Publisher
- Wiley
- Published
- 2004-02
- Volume
- 554
- Issue
- 3
- Pages
- 841-856
- ISSN
- 0022-3751 (ISSN-L)
- 1469-7793
- OpenAlex
- W1511863177
- Cited by
- 85
- References
- 73
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 5 · 2020: 5 · 2019: 2 · 2018: 5 · 2017: 5 · 2016: 2 · 2015: 5 · 2014: 4 · 2013: 4 · 2012: 10
- FWCI
- 0.95
- Type
- journal article
- Language
- en
- Open access
- green
- americanae.aecid.es
- Licence
- Locations
- The Journal of Physiology (publishedVersion)
- PubMed (publishedVersion)
- Americanae (AECID Library) (submittedVersion, other-oa)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- Funders
- Fondo Nacional de Desarrollo Científico y Tecnológico
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- fetal adrenal cortex, cortisol production, MT1 receptor, capuchin monkeys, continuous light exposure, neonatal cortisol, 3β-hydroxysteroid dehydrogenase, estradiol, ACTH, corticotropin-releasing factor, dehydroepiandrosterone sulfate
- MeSH terms
- Adrenal Glands, Adrenocorticotropic Hormone, Animals, Animals, Newborn, Cebus, Corticotropin-Releasing Hormone, Estradiol, Female, Embryonic and Fetal Development, Fetus, Hydrocortisone, Light, Melatonin, Osmolar Concentration, Pregnancy, Pregnancy, Animal, Transcription, Genetic, 3-Hydroxysteroid Dehydrogenases, Dehydroepiandrosterone Sulfate, Receptors, Melatonin
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