Abstract
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.