Piotrowska Katarzyna, Sluczanowska-Glabowska Sylwia, Kucia Magda, Bartke Andrzej, Laszczynska Maria, Ratajczak Mariusz Z
Department of Physiology, Pomeranian Medical University, Szczecin, Poland.
Folia Histochem Cytobiol. 2015;53(3):249-58. doi: 10.5603/fhc.a2015.0024. Epub 2015 Sep 8.
Overexpression of growth hormone (GH) leads to increase in insulin-like growth factor-1 (IGF-1) plasma level, stimulation of growth and increase in body size, organomegaly and reduced body fat. The action of GH affects all the organs and transgenic mice that overexpress bovine GH (bGH mice) serve as convenient model to study somatotropic axis. Male mice overexpressing GH are fertile, however, they show reduced overall lifespan as well as reproductive life span. The aim of the study was to evaluate the morphology and expression of androgen receptor (AR) and luteinizing hormone receptor (LHR) of bGH mice testes.
The experiment was performed on 6 and 12 month-old bGH male mice and 6 and 12 month-old wild type (WT) littermates (8 animals in each group). The morphology of testes was evaluated on deparaffinized sections stained by the periodic acid-Schiff (PAS) method. Expression of AR and LHR was investigated by immunohistochemistry and diameters of seminiferous tubules (ST) were measured on round cross sections of ST.
We noted larger testes in 6-month bGH mice as compared to normal WT littermates. The morpho-logical observations revealed essentially normal structure of Leydig cells, seminiferous epithelium and other morphological structures. However, some changes like tubules containing only Sertoli cells, tubules with arrested spermatogenesis or vacuoles in seminiferous epithelium could be attributed to the overexpression of GH. In contrast to WT mice, 12 month-old bGH mice displayed first symptoms of testicular aging. The immunoexpres-sion of AR and LHR was decreased in 12 month-old bGH males as compared to 12 month-old WT mice and younger animals.
Chronic exposure to elevated GH level accelerates testicular aging and thus potentially may change response of Leydig cells to LH and Sertoli and germ cells to testosterone.
生长激素(GH)的过度表达会导致胰岛素样生长因子-1(IGF-1)血浆水平升高,刺激生长,使体型增大、器官肿大并减少体脂。GH的作用影响所有器官,过表达牛生长激素的转基因小鼠(bGH小鼠)是研究生长激素轴的便捷模型。过表达GH的雄性小鼠具有生育能力,然而,它们的总体寿命以及生殖寿命缩短。本研究的目的是评估bGH小鼠睾丸雄激素受体(AR)和黄体生成素受体(LHR)的形态及表达。
实验在6个月和12个月大的bGH雄性小鼠以及6个月和12个月大的野生型(WT)同窝小鼠(每组8只动物)上进行。通过过碘酸希夫(PAS)法对脱蜡切片进行染色,评估睾丸的形态。通过免疫组织化学研究AR和LHR的表达,并在生精小管(ST)的圆形横截面上测量生精小管的直径。
我们发现,6个月大的bGH小鼠的睾丸比正常WT同窝小鼠的睾丸更大。形态学观察显示,睾丸间质细胞、生精上皮和其他形态结构基本正常。然而,一些变化,如仅含有支持细胞的小管、生精停滞的小管或生精上皮中的空泡,可能归因于GH的过度表达。与WT小鼠不同,12个月大的bGH小鼠出现了睾丸衰老的最初症状。与12个月大的WT小鼠和年轻动物相比,12个月大的bGH雄性小鼠中AR和LHR的免疫表达降低。
长期暴露于升高的GH水平会加速睾丸衰老,因此可能会改变睾丸间质细胞对促黄体生成素的反应以及支持细胞和生殖细胞对睾酮的反应。