Chowen J A, Argente J, Torres-Alemán I, González-Parra S, García-Segura L M
Instituto Cajal, CSIC, Madrid, Spain.
J Pediatr Endocrinol. 1993 Jul-Dec;6(3-4):211-8. doi: 10.1515/jpem.1993.6.3-4.211.
The growth hormone (GH) secretory pattern changes significantly throughout development in both male and female rats, becoming markedly sexually dimorphic after pubertal onset. This observation suggests that pubertal sex steroids play a 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 unknown. 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 its release from the anterior pituitary, i.e., somatostatin (SS) and growth hormone-releasing hormone (GHRH). The effects of neonatal testosterone and adult testosterone treatments on these two neuropeptide systems have also been studied. We have found that the synthetic capacity, as reflected in relative messenger RNA (mRNA) levels, of both SS and GHRH neurons changes throughout development in both male and female rats. These mRNA levels are also sexually dimorphic at certain times during maturation and, at least in the adult male, can be modulated by changes in testosterone levels. In support of the hypothesis that sex steroids play a role in the organization of the developing hypothalamus, we have shown that both estradiol and testosterone promote the survival of hypothalamic neurons in vitro. Preliminary in vivo studies indicate that the neonatal sex steroid environment may influence the number of GHRH neurons that are found in the adult brain, as well as their sensitivity to adult steroids.(ABSTRACT TRUNCATED AT 250 WORDS)
在雄性和雌性大鼠的整个发育过程中,生长激素(GH)的分泌模式会发生显著变化,在青春期开始后变得明显具有性别差异。这一观察结果表明,青春期性类固醇在这一现象的表现中起作用。新生儿类固醇环境也被证明与最终成年期GH分泌模式的形成密切相关,但其潜在机制仍不清楚。我们探讨了GH分泌模式的发育变化是否与调节其从前垂体释放的下丘脑神经肽的变化相关,即生长抑素(SS)和生长激素释放激素(GHRH)。还研究了新生儿睾酮和成年睾酮治疗对这两种神经肽系统的影响。我们发现,SS和GHRH神经元的合成能力(以相对信使核糖核酸(mRNA)水平反映)在雄性和雌性大鼠的整个发育过程中都会发生变化。这些mRNA水平在成熟过程中的某些时候也具有性别差异,并且至少在成年雄性中,可以受到睾酮水平变化的调节。为支持性类固醇在发育中的下丘脑组织中起作用这一假设,我们已表明雌二醇和睾酮都能在体外促进下丘脑神经元的存活。初步的体内研究表明,新生儿类固醇环境可能会影响成年大脑中GHRH神经元的数量及其对成年类固醇的敏感性。(摘要截断于250字)