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New insights regarding glucocorticoids, stress and gonadotropin suppression
Abstract
This review highlights our recent work investigating the inhibitory effects of acute, physiologic stress-like increases in cortisol on reproductive neuroendocrine activity in sheep, the mechanisms responsible for this suppression, and the relevance of enhanced glucocorticoid secretion to stress-induced inhibition of gonadotropin secretion in this species. Initial studies established that cortisol rapidly suppresses pulsatile luteinizing hormone secretion. In ovariectomized ewes, this inhibition reflects the reduction of pituitary responsiveness to gonadotropin-releasing hormone mediated by the type II glucocorticoid receptor, rather than the suppression in hypothalamic gonadotropin-releasing hormone release. Studies in ovary-intact ewes, however, uncovered an alternative mode of cortisol action. During the follicular phase of the estrous cycle, cortisol reduces luteinizing hormone pulse frequency, most likely via the inhibition of gonadotropin-releasing hormone pulsatility. Recent preliminary evidence in ovariectomized ewes demonstrates increased cortisol secretion is essential for disruption of pulsatile luteinizing hormone secretion in response to a psychosocial stress. Taken together, our observations reveal diverse inhibitory actions of cortisol on gonadotropin secretion and that this glucocorticoid is not only sufficient, but necessary for suppression of reproductive neuroendocrine activity in response to certain types of stress.
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“These effects are mediated through suppression of GnRH and GnRH receptor (GnRHR) synthesis, disruption in pituitary release of LH, and enhanced function of the gonadotropin-inhibitory hormone (GnIH; mammalian ortholog gene Rfrp3) neurons [21,23,24,25].”
From Stress and the HPA Axis: Balancing Homeostasis and Fertility. (2017) · cites this paper as [24]
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Metadata
- Authors
- BREEN, K., & KARSCH, F.
- Affiliations
- University of Michigan (US)
- Corresponding author
- BREEN, K
- ORCID
- BREEN, K
- Venue
- Frontiers in Neuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2006-07
- Volume
- 27
- Issue
- 2
- Pages
- 233-245
- ISSN
- 0091-3022 (ISSN-L)
- OpenAlex
- W1979908767
- Cited by
- 131
- References
- 93
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 5 · 2023: 9 · 2022: 4 · 2021: 5 · 2020: 4 · 2019: 5 · 2018: 7 · 2017: 6 · 2016: 9 · 2015: 8 · 2014: 8 · 2013: 8 · 2012: 4
- FWCI
- 6.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Frontiers in Neuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD-07048, R01HD030773, F32HD051360, HD051360, T32HD007048, HD-30773)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Keywords
- glucocorticoids, cortisol, stress, gonadotropin suppression, luteinizing hormone pulsatility, gonadotropin-releasing hormone, type II glucocorticoid receptor, pituitary responsiveness, sheep, psychosocial stress, follicular phase, estrous cycle
- MeSH terms
- Animals, Female, Gonadotropins, Hydrocortisone, Luteinizing Hormone, Gonadotropin-Releasing Hormone, Ovary, Periodicity, Pituitary Gland, Receptors, Glucocorticoid, Sheep, Stress, Physiological, Estrous Cycle
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