CONTROL OF THE TRANSCRIPTION OF THE GROWTH HORMONE-RELEASING HORMONE AND SOMATOSTATIN GENES BY SEX STEROIDS

The growth hormone (GH)-secretory pattern is markedly sexually dimorphic in the adult rat. These secretory patterns change significantly throughout development, becoming different between the sexes only after pubertal onset. This observation suggests that pubertal sex steroids play an important role in the manifestation of this phenomenon. The neonatal steroid environment has also been shown to be intricately involved in the generation of the final adult GH-secretory pattern, but the mechanisms underlying this effect remain less known. We have addressed the question as to whether the developmental changes in the GH-secretory pattern are correlated with changes in the hypothalamic neuropeptides that regulate GHs release from the anterior pituitary, i.e. somatostatin (SS) and growth hormone-releasing hormone (GHRH). In addition, the effects of neonatal testosterone and adult testosterone treatments on these two neuropeptide systems have been studied. We have found that the synthetic capacity, as reflected in relative levels of messenger RNA (mRNA), of both SS and GHRH neurons changes throughout development in both sexes and that they are sexually dimorphic at specific times during maturation. Furthermore, these mRNA levels can be modulated by changes in postpubertal testosterone levels. Preliminary studies indicate that the neonatal sex steroid environment also influences both GHRH and SS neurons. These studies suggest that both the neonatal and adult sex steroid environments influence the adult GH-secretory pattern, at least in part, by modulating GHRH and SS neurons.