Leptin increases L-type Ca2+ channel expression and GnRH-stimulated LH release in LbetaT2 gonadotropes.
Leptin, a mediator of long-term regulation of energy balance, has been implicated in the release of adenohypophyseal gonadotropins by regulating gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus. However, a direct effect of leptin on hormone release from gonadotropes remains virtually unexplored. In the current report, we assessed the long-term (48 h) actions of leptin on voltage-gated channel activity and luteinizing hormone (LH) production in mouse pituitary gonadotrope LbetaT2 cells. Electrophysiological recordings showed that leptin treatment significantly increased whole-cell patch-clamp Ba(2+) current through L-type Ca(2+) channels. Quantitative RT-PCR analysis revealed increased levels of L-type (alpha(1D)) Ca(2+) channel mRNA. Likewise, radioimmunoassays using specific antibodies provided evidence that leptin alone had no effect on LH release but did enhance GnRH-induced secretion of the hormone. Leptin had no apparent effects on LH gene transcription in absence of GnRH, as measured by transient transfection assays using a LH promoter-reporter gene and real-time RT-PCR. These observations suggest that leptin might affect LH release by acting directly on the gonadotropes, favoring hormone production by enhancing responsiveness to GnRH as a result of increased Ca(2+) channel expression.
Laboratory of Neuroendocrinology, Institute of Physiology, Autonomous University of Puebla (BUAP), Puebla, Mexico.
José E
JE
Avelino-Cruz
Amira
A
Flores
Jorge
J
Cebada
Pamela L
PL
Mellon
Ricardo
R
Felix
Eduardo
E
Monjaraz
D000818:Animals; D020746:Calcium Channels, L-Type / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D002460:Cell Line; D004357:Drug Synergism; D004594:Electrophysiology; D052681:Gonadotrophs / Q000187:drug effects* / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D020738:Leptin / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000378:metabolism*; D051379:Mice; D018408:Patch-Clamp Techniques; D054411:Receptors, Leptin / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D020746:Calcium Channels, L-Type; D020738:Leptin; D054411:Receptors, Leptin; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone