Leptin regulation of inward membrane currents, electrical activity and LH release in isolated bovine gonadotropes

Leptin, a peptide hormone produced by adipocytes, is recognized as one of the signals involved in the onset of reproductive activity. The leptin receptor has been found in hypothalamic neurons and pituitary gonadotropes, suggesting that the hormone may act at both sites to stimulate the secretion of GnRH and consequently, FSH and LH. In response to a stimulus such as a hypothalamic secretagogue, gonadotropes respond with changes in electrical activity, intracellular Ca²⁺ and hormone release. The main aim of this report was to investigate whether leptin promotes a change in the electrical and secretory activities of bovine gonadotropes. After 48 h of treatment with leptin (10 nM) significant changes in the action potential properties were observed in gonadotropes, which included an increase in amplitude, time-to-pike and post-hyperpolarization, as well as a decrease in firing threshold. Likewise, leptin induced a significant (∼1.3-fold) up-regulation of voltage-gated Na⁺ channel current density, and a selective increase (∼2.1-fold) in Ca²⁺ current density through high voltage-activated channels. Consistent with this, leptin enhanced GnRH-induced secretion of LH measured by ELISA. We suggest that leptin enhances membrane expression of voltage-gated Na⁺ and Ca²⁺ channels, which results in a modulation of the action potential properties and an increase in hormone release from gonadotropes.