Transient receptor potential (TRP) channel function in the reproductive axis |
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Affiliation: | 1. Department of Medical Physiology and Biophysic, Institute of Biomedicine of Sevilla, Sevilla, Spain;2. Inserm U1003, Equipe Labellisee par la Ligue Nationale Contre le Cancer; Laboratory of Excellence Ion Channel Science and Therapeutics; Universite de Lille 1, Sciences et Technologies, F-59655 Villeneuve d’Ascq, France;3. Department of Physiology (Cell Physiology Research Group), University of Extremadura, 10003-Cáceres, Spain |
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Abstract: | Transient receptor potential (TRP) channels play important functional roles in the signal transduction machinery of hormone-secreting cells and have recently been implicated in reproductive physiology. While expression studies have demonstrated TRP channel expression at all levels of the hypothalamic–pituitary–gonadal (hpg) axis, functional details about TRP channel action at the level of the individual cells controlling reproduction are just beginning to emerge. Canonical TRP (TRPC) channels are prominently expressed in the reproductive center of the neuroendocrine brain, i.e. in kisspeptin and gonadotropin-releasing hormone (GnRH) neurons. Kisspeptin neurons are depolarized by leptin via activation of TRPC channels and kisspeptin depolarizes GnRH neurons through TRPC4 activation. Recent studies have functionally identified TRPC channels also in gonadotrope cells in the anterior pituitary gland, which secrete gonadotropins in response to GnRH and thus regulate gonadal function. TRP channel expression in these cells exhibits remarkable plasticity and depends on the hormonal status of the animal. Subsequent functional analyses have demonstrated that TRPC5 in gonadotropes contributes to depolarization of the plasma membrane upon GnRH stimulation and increases the intracellular Ca2+ concentration via its own Ca2+ permeability and via the activation of voltage-gated Ca2+ channels. However, conditional gene targeting experiments will be needed to unambiguously dissect the physiological role of TRPC channels in the different cell types of the reproductive axis in vivo. |
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Keywords: | Reproduction Hypothalamus Pituitary Gonads TRP channels TRPC channels TRPC5 Knock-out Plasticity Gonadotropes Kisspeptin neurons GnRH neurons Genetic labeling GCaMP3 Whole-cell patch clamp RNA-sequencing Heat map |
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