ReviewTransient receptor potential (TRP) channel function in the reproductive axis

- TRP channels play important functional roles in cells controlling reproduction.
- Kisspeptin neurons are depolarized by leptin via activation of TRPC channels.
- Kisspeptin depolarizes GnRH neurons through TRPC4 activation.
- TRP channel expression in gonadotropes depends on the hormonal status.
- TRPC5 contributes to depolarization upon GnRH stimulation in gonadotropes.

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.

Transient receptor potential (TRP) channel function within the mammalian hypothalamus-pituitary-gonadal (hpg) axis. AP, anterior pituitary gland; AVPV, anteroventral periventricular nucleus of the hypothalamus; ARC, arcuate nucleus of the hypothalamus; FSH, follicle-stimulating hormone; GnRH, gonadotropin-releasing hormone; LH, luteinizing hormone; PP, posterior pituitary gland; TRPC, TRP canonical channel; TRPM, TRP melastatin channel; TRPV, TRP vanilloid channel. Figure was modified and reprinted from Mayer C & Boehm U, 2011 and Zahara A et al., 2012 [113,114] with permission from Nature Publishing Group and Oxford University Press.206