17β-oestradiol regulation of gonadotrophin-releasing hormone neuronal Excitability

17β-Oestradiol (E ₂) is essential for cyclical gonadotrophin-releasing hormone (GnRH) neuronal activity and secretion. In particular, E ₂ increases the excitability of GnRH neurones during the afternoon of pro-oestrus in the rodent, which is associated with increased synthesis and secretion of GnRH. It is well established that E ₂ regulates the activity of GnRH neurones through both presynaptic and postsynaptic mechanisms. E ₂ significantly modulates the mRNA expression of numerous ion channels in GnRH neurones and alters the associated endogenous conductances, including potassium (K _ATP, A-type) currents and low-voltage T-type and high-voltage L-type calcium currents. Notably, K _ATP channels are critical for maintaining GnRH neurones in a hyperpolarised state for recruiting the T-type calcium channels, which are important for burst firing in GnRH neurones. In addition, there are other critical channels contributing to burst firing pattern, including the small conductance Ca ²⁺-activated K ⁺ channels that may be modulated by E ₂. Despite these advances, the cellular mechanisms underlying the cyclical GnRH neuronal activity and GnRH release are largely unknown. Ultimately, the ensemble of both pre- and postsynaptic targets of the actions of E ₂ will dictate the excitability and activity pattern of GnRH neurones.