Somatostatin Messenger RNA in Hypothalamic Neurons Is Increased by Testosterone through Activation of Androgen Receptors and Not by Aromatization to Estradiol

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Abstract
Growth hormone (GH) secretory patterns are influenced by sex steroids, at least in part, through modulation of the secretion of hypothalamic somatostatin (SS) and GH-releasing hormone. Neurons in the periventricular nucleus (PeN) expressing the messenger RNA (mRNA) for SS are modulated by physiological levels of testosterone. However, it is uncertain whether testosterone’s action is mediated directly by androgen receptor activation or indirectly through aromatization to estradiol and subsequent binding to the estrogen receptor. We examined this question by evaluating the effectiveness of 17β-estradiol and the nonaromatizable androgen, dihydrotestosterone (DHT), to mimic the effects of testosterone. Adult male rats were castrated and implanted subcutaneously with a Silastic capsule that contained either testosterone, 17β-estradiol or DHT, or a sham capsule. Intact animals were sham-operated. We used in situ hybridization to assess the effect of these treatments on SS mRNA signal levels in individual neurons of the hypothalamus. Following castration, SS mRNA content was reduced in cells of the PeN (intact, 195 ± 12 grains/cell, vs. castrated, 139 ± 4 grains/cell). Replacement with physiological levels of testosterone prevented the decline in SS mRNA signal levels (castrated testosterone-replaced, 214 ± 15 grains/cell) as did replacement with the nonaromatizable androgen DHT (castrated DHT-replaced, 213 ± 16 grains/cell). Treatment with 17β-estradiol failed to prevent the postcastration decline in SS mRNA content (castrated estrogen-replaced, 145 ± 4 grains/cell). Castrated 17β-estradiol-treated animals were not significantly different from the castrated sham-treated animals (castrated, 139 ± 4 grains/cell, vs. castrated estrogen-replaced, 145 ± 4 grains/cell). These results show that, whereas testosterone and DHT prevented the postcastration decline in SS mRNA signal levels, 17β-estradiol had no such effect. Based on these observations, we conclude that the ability of testosterone to stimulate SS gene expression in neurons of the PeN is likely to be mediated through activation of androgen receptors and not through aromatization to estradiol.

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