Gonadal steroids reduce the density of axospinous synapses in the developing rat arcuate nucleus: An electron microscopy analysis

The developing brain is exquisitely sensitive to gonadal steroid hormones, which permanently differentiate the neural substrate during a critical deve lopmental period. One of the more striking sexual dimorphisms in the adult rat brain is synaptic patterning in the arcuate nucleus (ARC); females have twice the number of axospinous synapses as males (Matsumoto and Arai [1980 ] Brain Res. 190:238-242). Previously, rye have demonstrated that a similar dimorphism in spine densities on ARC dendrites is present as early as earl y as postnatal day 2 (PN2) in Golgi-impregnated rat brains (Mong et al. [19 99] J. Neurosci. 19:1464-1472). Males have 37% fewer dendritic spines than females. Moreover, these spine densities are sensitive to changes in the ho rmonal milieu such that males castrated on the day of birth have a signific ant increase in spine density, whereas females masculinized at birth by gon adal steroid exposure have a decreased dendritic spine density. One of the limitations of the Golgi technique is the inability to confirm the presence of synapses. The current study used quantitative electron microscopy and d emonstrated that testosterone exposure dramatically reduced axospinous syna pses in the ARC by PN 2. Males had 54% fewer and masculinized females had 7 7% fewer axospinous synapses than females (P < 0.05 and P < 0.01, respectiv ely). We previously reported that gonadal steroids induce coincident change s in neuronal and astrocyte morphology in the neonatal ARC (Mong et al., 19 99), and here confirm that these changes include an altered synaptic patter n that is strikingly similar to that observed in the adult (Matsumoto and A rai, 1980). J. Comp. Neurol. 432:259-267, 2001. (C) 2001 Wiley-Liss. Inc.