Ion Channels and Signaling in the Pituitary Gland

Abstract

Endocrine pituitary cells are neuronlike; they express numerous voltage-gated sodium, calcium, potassium, and chloride channels and fire action potentials spontaneously, accompanied by a rise in intracellular calcium. In some cells, spontaneous electrical activity is sufficient to drive the intracellular calcium concentration above the threshold for stimulus-secretion and stimulus-transcription coupling. In others, the function of these action potentials is to maintain the cells in a responsive state with cytosolic calcium near, but below, the threshold level. Some pituitary cells also express gap junction channels, which could be used for intercellular Ca(2+) signaling in these cells. Endocrine cells also express extracellular ligand-gated ion channels, and their activation by hypothalamic and intrapituitary hormones leads to amplification of the pacemaking activity and facilitation of calcium influx and hormone release. These cells also express numerous G protein-coupled receptors, which can stimulate or silence electrical activity and action potential-dependent calcium influx and hormone release. Other members of this receptor family can activate calcium channels in the endoplasmic reticulum, leading to a cell type-specific modulation of electrical activity. This review summarizes recent findings in this field and our current understanding of the complex relationship between voltage-gated ion channels, ligand-gated ion channels, gap junction channels, and G protein-coupled receptors in pituitary cells.

Prolactin and the physiological regulation of its secretion. A review

“…So, the function of lactotrophs is derived from structural polymorphism, local synthesis, divergent intracellular signaling pathways and target tissue (Ben-Jonathan et al, 1996;Stojilkovic et al, 2010). Indeed clonal cell line GH 3 produced prolactin and growth hormone and express thyrotropin releasing hormone (TRH), vasoactive intestinal polypeptide (VIP) and epidermal growth factor receptors, but not dopamine (DA) receptors (Ben-Jonathan et al, 1996;Stojilkovic et al, 2010). The 235-1 lactotroph cell line express the PRL gene.…”

“…They secrete PRL in CA ++ -dependent manner. Similarly, the MMQ cells (a unique prolactin-secreting rat pituitary cell line) secrete prolactin only in a CA ++ -dependent manner and express functionally DA-D 2 receptor, endothelin receptor (ETa) and oxytocin receptor (Stojilkovic et al, 2010). The PRL that is produced by different cell types can act in direct fashion as a growth factor, neurotransmitter or immunomodulator in auto or paracrine manner (Bole-Feysot et al, 1998).…”

“…Indeed, within seconds, DA increases potassium conductance and inactivates voltagesensitive calcium channels, resulting in membrane hyperpolarization and lowering the intracellular free calcium; within minutes to hours, DA decreases adenylcyclase activity, inosytol phosphate metabolism, arachidonic acid release and PRL gene expression. Within days, DA suppresses PRL cell proliferation (Stojilkovic et al, 2010). Withdrawal of DA after short application evokes a rapid rebound increase of basal PRL secretion (Ben-Jonathan and Hnasko, 2001).…”

“…DA actions in lactotrophs depend on the gonadal steroid milieu in female rats. Oestrogen decreases the expression of DA-D2 receptors and number of Gi/o immunoreactive lactotrophs (Livingstone et al, 1998;Stojilkovic et al, 2010). Also the stimulatory and inhibitory actions of DA on PRL release vary throughout the oestrous cycle and in the ovariectomized rats with the steroid replacement therapy (Stojilkovic et al, 2010).…”

“…Oestrogen decreases the expression of DA-D2 receptors and number of Gi/o immunoreactive lactotrophs (Livingstone et al, 1998;Stojilkovic et al, 2010). Also the stimulatory and inhibitory actions of DA on PRL release vary throughout the oestrous cycle and in the ovariectomized rats with the steroid replacement therapy (Stojilkovic et al, 2010). On the other hand, in vivo experiments often yield conflicting results because prolonged exposure and high doses of oestradiol increases PRL release, PRL gene expression and number of lactotrophs by activating PRL short loop feedback mechanism.…”