Prolactin regulation of gonadotropin-releasing hormone neurons to suppress luteinizing hormone secretion in mice
Abstract
Hyperprolactinemia causes infertility, but the mechanisms involved are not known. The present study aimed to determine whether and how prolactin may influence LH secretion in the adult female mouse. Using ovariectomized, estrogen-treated (OVX+E) mice, we found that 7 d of intracerebroventricular prolactin potently suppressed serum LH levels (P < 0.05). To examine whether this central action of prolactin may involve the GnRH neurons, the effects of acute and chronic prolactin on cAMP response element-binding protein phosphorylation (pCREB) in GnRH neurons were examined using dual-label immunocytochemistry. In diestrous and OVX+E mice, a single sc injection of ovine prolactin resulted in a significant (P < 0.05) doubling of the number of GnRH neurons expressing pCREB. OVX+E mice treated with five injections of ovine prolactin over 48 h showed a 4-fold increase in the number of GnRH neurons with pCREB. To determine whether GnRH neurons might be regulated directly by prolactin, we examined prolactin receptor (PRL-R) mRNA expression in green fluorescent protein-tagged GnRH neurons by single-cell RT-PCR. As a positive control, PRL-R mRNA was measured in arcuate dopaminergic neurons obtained from green fluorescent protein-tagged tyrosine hydroxylase neurons. Three of 23 GnRH neurons (13%) were identified to express PRL-R transcripts, whereas nine of 11 arcuate dopaminergic neurons (82%) were found to coexpress PRL-R mRNA. These data demonstrate that prolactin suppresses LH levels in the mouse, as it does in other species, and indicate that it acts centrally to regulate intracellular signaling within GnRH neurons. This is likely to occur, at least in part, through the direct regulation of a subpopulation of GnRH neurons.
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Only a few GnRH neurons express prolactin receptors, suggesting the existence of PRL-sensitive afferents.
“only a few GnRH neurons express prolactin receptors (13-15), suggesting the existence of PRL-sensitive afferents.”
From Kisspeptin Overcomes GnRH Neuronal Suppression Secondary to Hyperprolactinemia in Humans (2022) · cites this paper as [13]
Few GnRH neurons contain prolactin receptors.
“Initially, prolactin was thought to suppress LH secretion through suppression of GnRH release, although few GnRH neurons contain prolactin receptors (13).”
From Kisspeptin Overcomes GnRH Neuronal Suppression Secondary to Hyperprolactinemia in Humans (2022) · cites this paper as [13]
PRL receptors are localized on kisspeptin neurons.
“However, the localization of PRL receptors on kisspeptin neurons suggested that kisspeptin might mediate the inhibitory effects of hyperprolactinemia on GnRH secretion (13, 14).”
From Kisspeptin Overcomes GnRH Neuronal Suppression Secondary to Hyperprolactinemia in Humans (2022) · cites this paper as [13]
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- Authors
- Grattan, D. R., Jasoni, C. L., Liu, X., Anderson, G. M., & Herbison, A. E.
- Affiliations
- University of Otago (NZ)
- Corresponding author
- Grattan, David R.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2007-09-01
- Volume
- 148
- Issue
- 9
- Pages
- 4344-4351
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2109374960
- Cited by
- 145
- References
- 69
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 11 · 2023: 5 · 2022: 8 · 2021: 9 · 2020: 4 · 2019: 10 · 2018: 10 · 2017: 8 · 2016: 9 · 2015: 6 · 2014: 9 · 2013: 5 · 2012: 10
- FWCI
- 10.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Keywords
- prolactin, luteinizing hormone secretion, GnRH neurons, hyperprolactinemia, prolactin receptor, CREB phosphorylation, cAMP signaling, female fertility
- MeSH terms
- Animals, Cerebral Ventricles, Estrus, Homeostasis, Injections, Intraventricular, Luteinizing Hormone, Gonadotropin-Releasing Hormone, Male, Mice, Inbred C57BL, Neurons, Ovariectomy, Phosphorylation, Prolactin, Cyclic AMP Response Element-Binding Protein, Mice
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