Regulation of Sertoli cell number and activity by follicle-stimulating hormone and androgen during postnatal development in the mouse

Regulation of Sertoli cell number and activity by follicle-stimulating hormone and androgen during postnatal development in the mouse
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DOI:
10.1210/en.2003-1055
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发表时间:
2004-01-01
期刊:
影响因子:
4.8
通讯作者:
O'Shaughnessy, PJ
O'Shaughnessy, PJ
中科院分区:
医学2区
文献类型:
--
作者:
Johnston, H;Baker, PJ;O'Shaughnessy, PJ

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FSH和雄激素在支持细胞数量和功能的出生后发育中的作用已经使用缺乏FSH(FSHbetaKO)、FSH受体(FSHRKO)或雄激素受体(Tfm)的小鼠进行了研究。在出生和第5天,FSHRKO和FSHbetaKO小鼠的支持细胞数量是正常的,但在第20天和成年期显著减少。与此相反,Tfm小鼠的支持细胞数量在出生时减少,并保持显着低于正常到成年。通过测量11种不同的mRNA转录水平来确定支持细胞活性。从出生到成年,大多数转录本的表达增加,与一个显着的上升发生在d 5和10之间。在缺乏FSH刺激的动物中,mRNA表达(每个支持细胞测量)在第5天基本正常,但在第20天有7种转录本减少,在成年期有5种转录本减少。在Tfm小鼠的两个成绩单显示减少表达的第5天,和四个减少的第20天,虽然在成年Tfm小鼠的表达没有不同,在正常隐睾对照。结果表明:1)睾丸激素,而不是FSH,是胎儿和新生儿早期支持细胞增殖所必需的; 2)FSH和睾酮都调节支持细胞增殖的晚期阶段; 3)FSH对青春期和成年小鼠的支持细胞活性具有普遍的营养作用; 4)雄激素是青春期前发育期间特异性转录本表达所必需的。雄激素的特殊作用在成人中未观察到,尽管这些作用可能被隐睾症的作用所掩盖。
The roles of FSH and androgen in the postnatal development of Sertoli cell number and function have been investigated using mice that lack FSH (FSHbetaKO), FSH-receptors (FSHRKO), or androgen receptors (Tfm). At birth and d 5, Sertoli cell number was normal in FSHRKO and FSHbetaKO mice, but was significantly reduced on d 20 and in adulthood. In contrast, Sertoli cell number was reduced at birth in Tfm mice and remained significantly less than normal up to adulthood. Sertoli cell activity was determined through measurement of 11 different mRNA transcript levels. From birth to adulthood, the expression of most transcripts increased, with a significant rise occurring between d 5 and 10. In animals lacking FSH stimulation, mRNA expression (measured per Sertoli cell) was largely normal on d 5, but was reduced in seven transcripts on d 20 and in five transcripts at adulthood. In Tfm mice two transcripts showed reduced expression on d 5, and four were reduced on d 20, although expression in adult Tfm mice did not differ from that in normal cryptorchid controls. The results show that 1) testosterone, but not FSH, is required for Sertoli cell proliferation during fetal and early neonatal life; 2) FSH and testosterone both regulate the late stages of Sertoli cell proliferation; 3) FSH has a general trophic effect on Sertoli cell activity in the pubertal and adult mouse; and 4) androgens are required for specific transcript expression during prepubertal development. Specific effects of androgens were not seen in the adult, although these may be masked by the effects of cryptorchidism.