Effect of steroid milieu on gonadotropin-releasing hormone-1 neuron firing pattern and luteinizing hormone levels in male mice

GnRH neuronal function is regulated by gonadal hormone feedback. In males, testosterone can act directly or be converted to either dihydrotestosterone (DHT) or estradiol (E). We examined central steroid feedback by recording firing of green fluorescent protein (G FP) -identified GnRH neurons in brain slices from male mice that were intact, castrated, or castrated and treated with implants containing DHT, E-2, or E-2 +DHT. Castration increased LH levels. DHT or E-2 alone partially suppressed LH, whereas E-2+DHT reduced LH to intact levels. Despite the inhibitory actions on LH, the combination of E-2 +DHT increased GnRH neuron activity relative to other treatments, reflected in mean firing rate, amplitude of peaks in firing rate, and area under the curve of firing rate vs. time. Cluster8 was used to identify peaks in firing activity that may be correlated with hormone release. Castration increased the frequency of peaks in firing rate. Treatment with DHT failed to reduce frequency of these peaks. In contrast, treatment with E-2 reduced peak frequency to intact levels. The frequency of peaks in firing rate was intermediate in animals treated with E-2+DHT, perhaps suggesting the activating effects of this combination partially counteracts the inhibitory actions of E-2. These data indicate that E mediates central negative feedback in males primarily by affecting the pattern of GnRH neuron activity, and that androgens combined with estrogens have a central activating effect on GnRH neurons. The negative feedback induced by E-2+DHT to restore LH to intact levels may mask an excitatory central effect of this combination.