Effects of prolactin on intracellular calcium concentration and cell proliferation in human glioma cells

Abstract

Prolactin (PRL) has several physiological effects on peripheral tissues and the brain. This hormone acts via its membrane receptor (PRL-R) to induce cell differentiation or proliferation. Using reverse transcription-polymerase chain reaction (RT-PCR) combined with Southern blot analysis, we detected PRL-R transcripts in a human glioma cell line (U87-MG) and in primary cultured human glioblastoma cells. These transcripts were deleted or not in their extracellular domains. We examined the effects of PRL on intracellular free Ca2+ concentration ([Ca2+](i)) in these cells in order to improve our understanding of the PRL transduction mechanism, which is still poorly documented. [Ca2+](i) was measured by microspectrofluorimetry using indo-1 as the Ca2+ fluorescent probe. Spatiotemporal aspects of PRL-induced Ca2+ signals were investigated using high-speed fluo-3 confocal imaging. We found that physiological concentrations (0.4-4 nM) of PRL-stimulated Ca2+ entry and intracellular Ca2+ mobilization via a tyrosine kinase-dependent mechanism. The two types of Ca2+ responses observed were distinguishable by their kinetics: one showing a slow (type I) and the other a fast (type II) increase in [Ca2+](i). The amplitude of PRL-induced Ca2+ increases may be sufficient to provoke several physiological responses, such as stimulating proliferation. Furthermore, PRL induced a dose-dependent increase in [3H]thymidine incorporation levels and in cellular growth and survival, detected by the MTT method. These data indicate that PRL induced mitogenesis of human glioma cells.

Expression of the long form of the prolactin receptor in magnocellular oxytocin neurons is associated with specific prolactin regulation of oxytocin neurons

“…It is possible that this response also involves prolactin-induced activation of phosphoinositol-3 kinase and production of a range of inositol phosphate molecules (54). Similar prolactin-induced increases in intracellular Ca 2ϩ are also seen in glial cell lines (16,17) and neurons (29) that endogenously express the PRL-R. Hence, there is precedence for both rapid stimulatory and inhibitory actions of prolactin, and it is conceivable that either response could be induced, depending on the physiological state of the cell.…”

Reproductive and hormonal factors and risk of brain tumors in adult females

“…On the other hand, many hormonal changes occur following a first pregnancy, including a long-term lowering of levels of prolactin, estradiol, and androgens, and long-term higher levels of estriol. 32,44 -47 Prolactin has been shown to stimulate cell proliferation in cultured astrocytes and glioma cells, 48,49 , and it is conceivable that higher prolactin levels in nulliparous women may promote tumor growth.…”

Intermediate-conductance Ca2+-activated K+ channels (IKCa1) regulate human prostate cancer cell proliferation through a close control of calcium entry

“…For example, it has also been shown that calcium signaling is required for cell cycle progression from the G1/S phase through to mitosis (Hazelton et al, 1979;Tupper et al, 1980). Mitogenesis is accompanied by an increase in intracellular Ca 2 þ , so modifying intracellular Ca 2 þ alters proliferation and mitogenesis (Enomoto et al, 1998;Ducret et al, 2002).…”