Leptin activates cytosolic calcium responses through protein kinase-C dependent mechanism in immortalized RFamide-related peptide-3 neurons.
RFamide-related peptide-3 (RFRP-3), a mammalian ortholog of avian gonadotropin-inhibitory hormone (GnIH), seems to be an important regulator of the hypothalamus-pituitary-gonadal (HPG) reproductive axis. Leptin, a permissive hormonal regulator of fertility, provides energy signal to brain. According to current view, leptin does not act directly on gonadotrophin-releasing hormone (GnRH) neurons. RFRP-3 neurons have been shown to express leptin receptors. The goal of the present study was to examine whether leptin acts through RFRP-3 neurons to modulate activity of the GnRH neurons. For this aim, the effects of leptin on intracellular free Ca(2+) levels ([Ca(2+)]i) in RFRP-3 neurons were investigated by using in vitro calcium imaging system. In the present study, rHypoE-7 cell line was used as a model to explore the effects of leptin on RFRP-3 neurons. rHypoE-7 cells were placed on glass coverslip and loaded with 1 μM Fura-2 AM. [Ca(2+)]i responses were quantified by the changes in 340/380 ratio. Leptin (0.1-10 μM) caused increases in [Ca(2+)]i in a dose-dependent manner. The changes in [Ca(2+)]i were significantly attenuated by pre-treatment with protein kinase C inhibitor. These results demonstrate that leptin activates intracellular calcium signaling in RFRP-3 neurons through PKC-dependent pathway, and thus leptin may exert its effect on GnRH neurons by means of RFRP-3 cells.
['Ozcan|Mete|M|', 'Saatci|Tugrul|T|', 'Ayar|Ahmet|A|', 'Canpolat|Sinan|S|', 'Kelestimur|Haluk|H|']
D000818:Animals D020013:Calcium Signaling D002460:Cell Line D007987:Gonadotropin-Releasing Hormone D007028:Hypothalamic Hormones D020738:Leptin D009474:Neurons D011493:Protein Kinase C D051381:Rats
Leptin Protein kinase-C RFamide-related peptide-3 neurons Calcium signaling