Davies J S, Thompson N M, Christian H C, Pinilla L, Ebling F J P, Tena-Sempere M, Wells T
School of Biosciences, Cardiff University, Cardiff, UK.
J Neuroendocrinol. 2006 Oct;18(10):719-31. doi: 10.1111/j.1365-2826.2006.01467.x.
Growth hormone (GH) is known to regulate peripheral components of the hypothalamo-pituitary gonadal (HPG) axis, but it remains unclear whether GH exerts a significant influence on the activity of the hypothalamo-pituitary components of the HPG axis. In this study, we investigated the development of HPG axis function in the male transgenic growth retarded (Tgr) rat, a model of moderate systemic GH deficiency caused by hypothalamic expression of human (h)GH. Impaired postnatal somatotroph expansion and moderate GH deficiency in male Tgr rats were accompanied by a two- to three-fold increase in pituitary gonadotrophin content, but without a significant change in the pituitary gonadotroph population. A three- to nine-fold elevation in basal circulating luteinising hormone concentration was seen in postpubertal Tgr rats, with a smaller increase in follicle-stimulating hormone. Despite this hypergonadotrophism, there was no corresponding increase in steroidogenic (circulating testosterone and seminal vesicle weights) or gametogenic (spermatozoa counts in seminiferous tubules) activity in the postpubertal Tgr testis. Following puberty, the plasma leptin concentration also became progressively elevated in Tgr males. Circulating gonadotrophin and leptin levels were normalised in Tgr rats by peripheral physiological replacement of rat GH, but plasma testosterone concentration was unaffected. These results confirm that hGH exerts a positive influence on the central control of gonadotrophin secretion in the Tgr rat, but the absence of a corresponding elevation in the steroidogenic or gametogenic function of the Tgr testis implies that the peripheral GH/insulin-like growth factor I axis may also exert a permissive influence on testicular function. The relative contribution of somatogenic and lactogenic mechanisms and the potential influence of elevated leptin and decreased sensitivity to androgen feedback to the development of postpubertal hypergonadotrophism in Tgr males remain to be determined.
已知生长激素（GH）可调节下丘脑 - 垂体 - 性腺（HPG）轴的外周组成部分，但GH是否对HPG轴的下丘脑 - 垂体组成部分的活性有显著影响仍不清楚。在本研究中，我们调查了雄性转基因生长迟缓（Tgr）大鼠中HPG轴功能的发育情况，该大鼠是一种由人（h）GH在下丘脑表达引起的中度全身性GH缺乏模型。雄性Tgr大鼠出生后生长激素细胞扩张受损和中度GH缺乏伴随着垂体促性腺激素含量增加两到三倍，但垂体促性腺激素细胞数量没有显著变化。在青春期后的Tgr大鼠中，基础循环促黄体生成素浓度升高了三到九倍，促卵泡生成素的升高幅度较小。尽管存在这种性腺功能亢进，但青春期后Tgr睾丸的类固醇生成（循环睾酮和精囊重量）或配子生成（曲细精管中的精子计数）活性没有相应增加。青春期后，Tgr雄性大鼠的血浆瘦素浓度也逐渐升高。通过外周生理性替代大鼠GH，Tgr大鼠的循环促性腺激素和瘦素水平恢复正常，但血浆睾酮浓度不受影响。这些结果证实，hGH对Tgr大鼠促性腺激素分泌的中枢控制有积极影响，但Tgr睾丸的类固醇生成或配子生成功能没有相应升高，这意味着外周GH/胰岛素样生长因子I轴也可能对睾丸功能发挥允许作用。生体机制和泌乳机制的相对贡献以及瘦素升高和雄激素反馈敏感性降低对Tgr雄性大鼠青春期后性腺功能亢进发展的潜在影响仍有待确定。
