In vitro paradigms for the study of GnRH neuron function and estrogen effects

The elaboration of in vitro paradigms has enabled direct study of GnRH secretion and the regulation of this process. Common findings using different models are the pulsatile nature and calcium-dependency of GnRH secretion, the excitatory effect of glutamate, and the inhibitory or excitatory effect of GABA. Among the different paradigms, the fetal olfactory placode cultures exhibit the unique property of migration in vitro and may retain the capacity to undergo maturational changes in vitro. The short-term incubation of hypothalamic explants obtained at different ages enables one to study developmental changes as well. Estrogens may have important roles in the regulation of GnRH function and can act indirectly via the neighboring neuronal/glial apparatus and directly on GnRH neurons at the cell body and terminal levels. A direct effect is supported by the recent localization of ERalpha and ERbeta transcripts in GnRH neurons using most paradigms. Discrepant effects of estrogens on GnRH neurons were observed since GnRH biosynthesis is inhibited while GnRH secretion can be either stimulated, unaffected, or reduced. It is likely that the regulatory role of sex steroids including estradiol is very complex since it could involve direct and indirect effects on GnRH neurons through genomic and/or non-genomic mechanisms.