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The effects of androgen on the density of spine synapses on pyramidal neurons in the CA1 area of the hippocampus were studied in male rats. Gonadectomy (GDNX) had no significant effect on the number of CA1 pyramidal cells but reduced CA1 spine synapse density by almost 50% (to 0.468 ± 0.018 spine synapses/μm3) compared with sham-operated controls (0.917 ± 0.06 spine synapses/μm3). Treatment of GDNX rats with testosterone propionate (500 μg/d, s.c., 2 d) increased spine synapse density to levels (1.01 ± 0.026 spine synapses/μm3) comparable with intact males. A similar increase in synapse density (1.013 ± 0.05 spine synapses/μm3) was observed in GDNX animals after treatment with dihydrotestosterone (DHT) (500 μg/d, s.c., 2 d) but not after estradiol (10 μg/d, s.c., 2 d; 0.455 ± 0.02 spine synapse/μm3). These data indicate that testosterone is important for maintenance of normal spine synapse density in the CA1 region of the male rat hippocampus. The comparable responses to testosterone and the non-aromatizable androgen DHT, coupled with the lack of response to estradiol, suggest that testosterone acts directly on hippocampal androgen receptors rather than indirectly via local estrogen biosynthesis.

Gonadal Hormones Affect Spine Synaptic Density in the CA1 Hippocampal Subfield of Male Rats