Prenatal testosterone masculinizes synaptic input to gonadotropin-releasing hormone neurons in sheep

In sheep, the control of tonic and surge GnRH secretion is sexually differentiated by testosterone in utero. However, GnRH neurons are not sexually dimorphic with respect to number, distribution, or gross morphology. Therefore, this study tested the hypothesis that prenatal steroids influence synaptic input to GnRH neurons. We compared the number of synapses on GnRH neurons from male, female, and androgenized female lambs (n = 5 each). Androgenized females were exposed to testosterone during mid-gestation. Yearling lambs were perfused, and GnRH neurons were visualized using the LR-1 antibody. Five to seven GnRH neurons from the rostral preoptic area in each animal were viewed at the ultrastructural level. Afferent synapses and glial ensheathment on each neuron were counted in a single section through the plane of the nucleus. GnRH neurons from females received approximately twice as many contacts (3.6 +/- 0.7 synapses/100 microm plasma membrane) as those from male lambs (1.6 +/- 0.3; p < 0.05), similar to previous reports in rats. In addition, the number of synapses on GnRH neurons from androgenized female lambs (1.5 +/- 0.5) was similar to that from male lambs, suggesting that prenatal steroids give rise to sex differences in synaptic input to GnRH neurons.