Differential actions of prolactin on electrical activity and intracellular signal transduction in hypothalamic neurons
Abstract
In many tissues, including brain, prolactin action is predominantly mediated by the Janus kinase/signal transducer and activator of transcription (STAT) signal transduction pathway, leading to changes in gene transcription. However, prolactin can also exert rapid actions on electrical activity of hypothalamic neurons. Here, we investigate whether both responses occur in a single cell type, focusing on three specific populations known to be influenced by prolactin: GnRH neurons, tuberoinfundibular dopamine (TIDA) neurons, and neurons in the anteroventral-periventricular nucleus in female mice. We performed phosphorylated STAT5 (pSTAT5) immunohistochemistry to identify prolactin-responsive neurons after in vivo prolactin treatment. In addition, we carried out in vitro electrophysiology in slices from transgenic mice expressing green fluorescent protein driven by the GnRH or tyrosine hydroxylase promoters as well as from C57BL/6J mice to assess acute electrical responses to prolactin. Approximately 88% of TIDA neurons expressed pSTAT5 in diestrous mice, rising to 97% after prolactin treatment. All TIDA neurons also showed a rapid increase in firing rate after prolactin treatment. In contrast, very few GnRH neurons (11%) showed pSTAT5 in response to prolactin, and none showed a change in electrical activity. Finally, in the anteroventral-periventricular nucleus, most neurons (69%) responded to prolactin treatment with an increase in pSTAT5, but only 2/38 (∼5%) showed changes in electrical activity in response to prolactin. These observations show that prolactin recruits different combinations of electrical and transcriptional responses in neurons depending upon their anatomical location and phenotype. This may be critical in establishing appropriate responses to prolactin under different physiological conditions.
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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 [15]
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Recent Findings on Hyperprolactinemia and its Pathological Implications: A Literature Review
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Pituitary Hormones and Orofacial Pain
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Parenting as a model for behavioural switches
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New insights into human prolactin pathophysiology: genomics and beyond
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Prolactin Assays and Regulation of Secretion: Animal and Human Data
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The Hypothalamic Arcuate Nucleus Dopaminergic Neurons: More Than Just Prolactin Secretion
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Prolactin fractions from lactating rats elicit effects upon sensory spinal cord cells of male rats
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The median eminence detects and responds to circulating prolactin in the male mouse
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Lactation and the Control of the Prolactin Secretion
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Abbreviations Used for Major Brain Regions
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Numan, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.002.0004
Plasticity and neuromodulation of neuroendocrine nerve terminals
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Hyperprolactinemia and Brain Health: Exploring the Gut-Brain Axis and Therapeutic Strategies
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- Authors
- Brown, R. S. E., Piet, R., Herbison, A. E., & Grattan, D. R.
- Affiliations
- Centre for Neuroendocrinology and Departments of Anatomy (R.S.E.B., D.R.G.), Dunedin 9016, New Zealand
- University of Otago (NZ)
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2012-03-13
- Volume
- 153
- Issue
- 5
- Pages
- 2375-2384
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2076573882
- Cited by
- 91
- References
- 64
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 4 · 2022: 5 · 2021: 3 · 2020: 26 · 2019: 10 · 2018: 9 · 2017: 3 · 2016: 6 · 2015: 4 · 2014: 8 · 2013: 5
- FWCI
- 6.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Keywords
- prolactin, hypothalamic neurons, STAT5 phosphorylation, neuronal electrical activity, GnRH neurons, tuberoinfundibular dopamine neurons, anteroventral periventricular nucleus, female mice
- MeSH terms
- Animals, Dopamine, Female, Hypothalamus, Neural Conduction, Neurons, Phosphorylation, Prolactin, Receptors, Prolactin, Tyrosine 3-Monooxygenase, Signal Transduction, STAT5 Transcription Factor, Mice, Dopaminergic Neurons
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