Maiter D, Koenig J I, Kaplan L M
Department of Neurology, Massachusetts General Hospital, Boston.
Endocrinology. 1991 Apr;128(4):1709-16. doi: 10.1210/endo-128-4-1709.
The sexual dimorphism characterizing GH secretion in the rat is thought to be related to differences in the hypothalamic synthesis and release of the GH-regulating peptides, GH-releasing hormone (GHRH), and somatostatin. Therefore, the influence of gender and sex steroid hormones on hypothalamic expression of the GHRH gene in adult rats were examined. GHRH messenger RNA (mRNA) levels were measured in individual rat hypothalami by Northern hybridization analysis using a 32P-labeled complementary DNA encoding rat GHRH. Destruction of hypothalamic GHRH neurons by neonatal treatment with monosodium glutamate caused similar 3-fold reductions in the levels of GHRH mRNA in adult male and female animals. In three separate experiments, hypothalamic GHRH mRNA concentrations in male rats were 2- to 3-fold greater than in randomly cycling females (four or five rats per group; P less than 0.01). In spite of the greater abundance of GHRH mRNA abundance in the male rat hypothalamus, circulating gonadal steroids lacked the ability to modulate GHRH gene expression in adult animals, since neither gonadectomy nor pharmacological sex steroid replacement changed GHRH mRNA levels in the hypothalamus of male and female adult rats. Furthermore, GHRH mRNA concentrations in female rats were similar during the proestrus, estrus, and diestrus phase of the estrous cycle. Also, GH inhibited hypothalamic GHRH gene expression in a sex-specific manner. Exposure to high levels of GH secreted by the MtTW15 tumor for 4 weeks reduced GHRH mRNA concentrations 7-fold in male rats (P less than 0.001) but only 2-fold in females (P less than 0.05). These studies demonstrate that GHRH gene expression in the rat hypothalamus is sexually dimorphic. Basal mRNA levels are greater in male rats, and expression in male hypothalami is more sensitive to feedback inhibition by GH than expression in females. There is no evidence for regulation of GHRH mRNA levels by either testosterone or estrogen in adult rats. These gender differences in GHRH gene expression likely contribute to the generation of a sex-specific pattern of GH secretion.
大鼠生长激素（GH）分泌所具有的性别差异被认为与下丘脑合成及释放的GH调节肽、生长激素释放激素（GHRH）和生长抑素的差异有关。因此，研究了性别和性类固醇激素对成年大鼠下丘脑GHRH基因表达的影响。使用编码大鼠GHRH的32P标记互补DNA，通过Northern杂交分析测定个体大鼠下丘脑内的GHRH信使核糖核酸（mRNA）水平。新生期用谷氨酸单钠处理破坏下丘脑GHRH神经元，导致成年雄性和雌性动物的GHRH mRNA水平出现类似的3倍降低。在三个独立实验中，雄性大鼠下丘脑GHRH mRNA浓度比随机发情的雌性大鼠高2至3倍（每组4或5只大鼠；P<0.01）。尽管雄性大鼠下丘脑GHRH mRNA丰度更高，但循环中的性腺类固醇缺乏调节成年动物GHRH基因表达的能力，因为性腺切除和药理学性类固醇替代均未改变成年雄性和雌性大鼠下丘脑的GHRH mRNA水平。此外，雌性大鼠在发情周期的动情前期、发情期和动情间期的GHRH mRNA浓度相似。而且，GH以性别特异性方式抑制下丘脑GHRH基因表达。暴露于MtTW15肿瘤分泌的高水平GH 4周，使雄性大鼠的GHRH mRNA浓度降低7倍（P<0.001），而雌性大鼠仅降低2倍（P<0.05）。这些研究表明，大鼠下丘脑的GHRH基因表达具有性别差异。基础mRNA水平在雄性大鼠中更高，并且雄性下丘脑的表达比雌性对GH的反馈抑制更敏感。没有证据表明成年大鼠中睾酮或雌激素可调节GHRH mRNA水平。GHRH基因表达中的这些性别差异可能有助于产生性别特异性的GH分泌模式。
