Galanin gene expression in hypothalamic GnRH-containing neurons of the rat: a model for autocrine regulation

Increasing experimental evidence has accumulated to suggest that galanin may be one of the essential regulators in the reproductive system of the rat. Galanin is a polypeptide which has been found in hypothalamic neurons, where it is colocalized with GnRH. GnRH-containing cells begin to express detectable levels of galanin mRNA at the onset of puberty, and this process is dependent on the presence of the gonads. This indicates that the induction of galanin expression in GnRH neurons is an important requirement for the maturation of the reproductive axis. The pattern of co-expression of galanin and GnRH in hypothalamic neurons is sexually dimorphic, with much greater galanin mRNA content in the GnRH neurons of females compared to males. The role of galanin may therefore be important in reproductive processes unique to the female, such as the LH surge and ovulation. During the estrous cycle, galanin mRNA levels are enhanced in GnRH neurons at the time of the LH surge. This suggests a tight coupling of galanin biosynthesis and release to the activity state of the GnRH neurons. Expression of the galanin gene in GnRH neurons is regulated by ovarian sex steroids: estradiol appears to support the basal expression of galanin mRNA in GnRH neurons. In addition, estradiol is capable of dramatically increasing galanin gene expression, either when administered alone or in conjunction with progesterone. Nevertheless, neuronal activation with concomitant induction of galanin gene expression requires transsynaptic signals by afferent inputs impinging on the GnRH cells. Galanin may serve as a critical autocrine regulator for the activity of GnRH cells, in that it may be co-released with GnRH and act presynaptically on the GnRH neuron, helping to shape GnRH release into distinct pulses. Collectively, these observations indicate that galanin gene expression in GnRH neurons may represent a pivotal signal for the activation of the neuroendocrine reproductive axis.