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Trpc5 deficiency causes hypoprolactinemia and altered function of oscillatory dopamine neurons in the arcuate nucleus
- Source :
- Proceedings of the National Academy of Sciences. 116:15236-15243
- Publication Year :
- 2019
- Publisher :
- Proceedings of the National Academy of Sciences, 2019.
-
Abstract
- Dopamine neurons of the hypothalamic arcuate nucleus (ARC) tonically inhibit the release of the protein hormone prolactin from lactotropic cells in the anterior pituitary gland and thus play a central role in prolactin homeostasis of the body. Prolactin, in turn, orchestrates numerous important biological functions such as maternal behavior, reproduction, and sexual arousal. Here, we identify the canonical transient receptor potential channel Trpc5 as an essential requirement for normal function of dopamine ARC neurons and prolactin homeostasis. By analyzing female mice carrying targeted mutations in the Trpc5 gene including a conditional Trpc5 deletion, we show that Trpc5 is required for maintaining highly stereotyped infraslow membrane potential oscillations of dopamine ARC neurons. Trpc5 is also required for eliciting prolactin-evoked tonic plateau potentials in these neurons that are part of a regulatory feedback circuit. Trpc5 mutant females show severe prolactin deficiency or hypoprolactinemia that is associated with irregular reproductive cyclicity, gonadotropin imbalance, and impaired reproductive capabilities. These results reveal a previously unknown role for the cation channel Trpc5 in prolactin homeostasis of female mice and provide strategies to explore the genetic basis of reproductive disorders and other malfunctions associated with defective prolactin regulation in humans.
- Subjects :
- endocrine system
medicine.medical_specialty
Lactation Disorders
Biology
TRPC5
Membrane Potentials
Mice
Anterior pituitary
Dopamine
Internal medicine
medicine
Animals
Homeostasis
Humans
hypothalamus
TRPC Cation Channels
Feedback, Physiological
Multidisciplinary
Dopaminergic Neurons
Reproduction
Arcuate Nucleus of Hypothalamus
Genetic Diseases, Inborn
Prolactin deficiency
medicine.disease
Trpc5 channelopathy
Prolactin
Hypoprolactinemia
Endocrinology
medicine.anatomical_structure
Gene Expression Regulation
PNAS Plus
Hypothalamus
Mutation
HC-070
Female
dopamine
Arousal
Gonadotropins
hormones, hormone substitutes, and hormone antagonists
Signal Transduction
medicine.drug
Subjects
Details
- ISSN :
- 10916490 and 00278424
- Volume :
- 116
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences
- Accession number :
- edsair.doi.dedup.....178a27362360fcfa302ab8e6cc9bd246