Modulation of estrogen receptors during development inhibits neurogenesis of precursors to GnRH-1 neurones: in vitro studies with explants of ovine olfactory placode.

The aim of the present study was to explore the putative effects of agonists and antagonists of the estradiol receptor on the early phase of GnRH-1 neuron development. To address this question we used an in vitro model of GnRH-1 neurons using cultured olfactory placode from sheep embryos on day 26 of gestation. Previous studies on this model have shown that in vitro the development of GnRH-1 neurons mimics in vivo development up to the start of pulsatile GnRH-1 secretion, To address the effects of modulating the estrogen receptor, cultures were treated with the endogenous and synthetic ligands of estradiol receptors: 17beta-estradiol, 17alpha-estradiol and tamoxifen. Neurogenesis was measured by incorporation of [(3)H]-thymidine. Morphometric parameters were evaluated by image analysis. The main results are that antagonism of estradiol receptors induced an important decrease in neurogenesis but had little effect on morphometric parameters, suggesting that during this early phase of development, maternal estrogens are important to achieve correct development of the GnRH-1 neuronal network.