O'Shaughnessy Peter J, Mitchell Rod T, Monteiro Ana, O'Hara Laura, Cruickshanks Lyndsey, der Grinten Hedi Claahsen-van, Brown Pamela, Abel Margaret, Smith Lee B
College of Medical, Veterinary and Life Sciences, Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, G61 1QH, Glasgow, UK.
MRC Centre for Reproductive Health, University of Edinburgh, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK.
BMC Dev Biol. 2019 Apr 17;19(1):8. doi: 10.1186/s12861-019-0189-5.
The interstitium of the mouse testis contains Leydig cells and a small number of steroidogenic cells with adrenal characteristics which may be derived from the fetal adrenal during development or may be a normal subset of the developing fetal Leydig cells. Currently it is not known what regulates development and/or proliferation of this sub-population of steroidogenic cells in the mouse testis. Androgen receptors (AR) are essential for normal testicular function and in this study we have examined the role of the AR in regulating interstitial cell development.
Using a mouse model which lacks gonadotropins and AR (hpg.ARKO), stimulation of luteinising hormone receptors in vivo with human chorionic gonadotropin (hCG) caused a marked increase in adrenal cell transcripts/protein in a group of testicular interstitial cells. hCG also induced testicular transcripts associated with basic steroidogenic function in these mice but had no effect on adult Leydig cell-specific transcript levels. In hpg mice with functional AR, treatment with hCG induced Leydig cell-specific function and had no effect on adrenal transcript levels. Examination of mice with cell-specific AR deletion and knockdown of AR in a mouse Leydig cell line suggests that AR in the Leydig cells are likely to regulate these effects.
This study shows that in the mouse the androgen receptor is required both to prevent development of testicular cells with adrenal characteristics and to ensure development of an adult Leydig cell phenotype.
小鼠睾丸间质包含睾丸间质细胞和少量具有肾上腺特征的类固醇生成细胞,这些细胞可能在发育过程中源自胎儿肾上腺,也可能是发育中的胎儿睾丸间质细胞的正常亚群。目前尚不清楚是什么调节小鼠睾丸中这群类固醇生成细胞的发育和/或增殖。雄激素受体(AR)对于正常睾丸功能至关重要,在本研究中,我们研究了AR在调节间质细胞发育中的作用。
使用缺乏促性腺激素和AR的小鼠模型(hpg.ARKO),用人绒毛膜促性腺激素(hCG)体内刺激促黄体生成素受体,导致一组睾丸间质细胞中肾上腺细胞转录本/蛋白显著增加。hCG还诱导了这些小鼠中与基本类固醇生成功能相关的睾丸转录本,但对成年睾丸间质细胞特异性转录本水平没有影响。在具有功能性AR的hpg小鼠中,用hCG治疗诱导了睾丸间质细胞特异性功能,对肾上腺转录本水平没有影响。对具有细胞特异性AR缺失的小鼠以及在小鼠睾丸间质细胞系中敲低AR的研究表明,睾丸间质细胞中的AR可能调节这些效应。
本研究表明,在小鼠中,雄激素受体对于防止具有肾上腺特征的睾丸细胞发育以及确保成年睾丸间质细胞表型的发育都是必需的。