Abstract
Lactotrophs are one of the five secretory anterior pituitary cell types specialized to synthesize and release prolactin. In vitro, these cells fire action potentials (APs) spontaneously and the accompanied Ca2+ transients are of sufficient amplitude to keep the exocytotic pathway, the transcription of prolactin gene, and de novo hormone synthesis continuously active. Basal cyclic nucleotide production is also substantial in cultured cells but not critical for the APs secretion/transcription coupling in lactotrophs. However, elevated intracellular cAMP levels enhance the excitability of lactotrophs by stimulating the depolarizing non-selective cationic hyperpolarization-activated cyclic nucleotide-regulated and background channels, whereas cGMP inhibits it by activating Ca2+-controlled K+ channels. Elevated cAMP also modulates prolactin release downstream of Ca2+ influx by changing the kinetic of secretory pores: stimulate at low and inhibit at high concentrations. Induction of prolactin gene and lactotroph proliferation is also stimulated by elevated cAMP through protein kinase A. Together, these observations suggest that in lactotrophs cAMP exhibits complex regulatory effects on voltage-gated Ca2+ influx and Ca2+-dependent cellular processes.
Highlights
Lactotrophs are the anterior pituitary secretory cell type specialized to synthesize and release prolactin (PRL), a hormone with roles in reproduction, lactation, and metabolism
Signaling function in lactotrophs is facilitated by numerous Ca2+mobilizing receptors expressed in these cells, and their activation transiently inhibits electrical activity, followed by a sustained increase in the firing frequency
Experiments with IBMX, forskolin, and cell-permeable cAMP analogs show that cAMP directly stimulates HCN channels and through PKA stimulates still unidentified Nab channels, and probably influences gating of several other channels
Summary
Lactotrophs are the anterior pituitary secretory cell type specialized to synthesize and release prolactin (PRL), a hormone with roles in reproduction, lactation, and metabolism. Spontaneous electrical activity and AP secretion coupling are sufficient to keep lactotrophs operative in the absence of any stimuli due to refilling of the PRL secretory pool by Ca2+-dependent Prl expression and de novo protein synthesis.
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