Progesterone increases dynorphin A concentrations in cerebrospinal fluid and preprodynorphin messenger ribonucleic acid levels in a subset of dynorphin neurons in the sheep
Abstract
Recent studies suggest that the endogenous opioid peptide, dynorphin, is an important mediator of progesterone negative feedback on GnRH pulse frequency in the ewe. These experiments tested this hypothesis by examining the effects of progesterone on dynorphin A concentrations in cerebrospinal fluid (CSF) collected from the third ventricle and expression of preprodynorphin (PPD) mRNA in hypothalamic nuclei. CSF was collected every 10 min for 5 h in three groups of ewes: 1) ovary-intact ewes during the luteal phase (d 6-7 of estrous cycle); 2) ewes 6-7 d after ovariectomy (OVX); and 3) OVX ewes treated for 6-7 d with implants that produced luteal-phase progesterone levels. Diencephalic tissue from these ewes was then collected and processed for in situ hybridization using an ovine cDNA probe against PPD. Progesterone treatment increased dynorphin A concentrations in CSF over that observed in untreated OVX ewes; CSF dynorphin A concentrations in ovary-intact ewes were midway between the other groups. OVX significantly decreased the number of PPD mRNA-expressing cells in the preoptic area (POA), anterior hypothalamic area (AHA), and arcuate nucleus (ARC), with no change seen in any other PPD-expressing nuclei. Progesterone treatment of OVX ewes restored PPD expression in the POA and AHA to levels seen in luteal-phase animals but had no effect on PPD expression in the ARC. These results are consistent with the hypothesis that progesterone acts via dynorphin neurons to inhibit pulsatile GnRH secretion and point to dynorphin neurons in the POA, AHA, and ARC as potential mediators of this action during the luteal phase.
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Ovariectomy decreased dynorphin gene expression in the arcuate nucleus of the ewe, but ovariectomized mice exhibited increased dynorphin mRNA compared to estrogen treated mice.
“In parallel to the findings in postmenopausal women, ovariectomy decreased dynorphin gene expression in the arcuate nucleus of the ewe (Foradori et al., 2005), but ovariectomized mice exhibited increased dynorphin mRNA, compared to estrogen treated mice (Navarro et al., 2009).”
From Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes (2013) · cites this paper as Foradori et al., 2005
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- Authors
- Foradori, C. D., Goodman, R. L., Adams, V. L., Valent, M., & Lehman, M. N.
- Affiliations
- University of Cincinnati (US)
- West Virginia University (US)
- Corresponding author
- Lehman, Michael N.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2005-04
- Volume
- 146
- Issue
- 4
- Pages
- 1835-1842
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2014359319
- Cited by
- 123
- References
- 45
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 6 · 2023: 1 · 2022: 5 · 2021: 6 · 2020: 6 · 2019: 8 · 2018: 9 · 2017: 7 · 2016: 9 · 2015: 7 · 2014: 7 · 2013: 10 · 2012: 9
- FWCI
- 4.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (T32DK-59803, T32DK059803)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01 HD 39916, R01HD039916)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Keywords
- progesterone, dynorphin A, cerebrospinal fluid, GnRH pulsatility, negative feedback, hypothalamus, preoptic area, anterior hypothalamic area, arcuate nucleus, ovariectomy, luteal phase, sheep, endogenous opioids
- MeSH terms
- Animals, Dynorphins, Female, Hypothalamus, Ovariectomy, Progesterone, Protein Precursors, RNA, Messenger, Sheep
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