Inhibitory roles of the mammalian GnIH ortholog RFRP3 in testicular activities in adult mice
Inhibitory roles of the mammalian GnIH ortholog RFRP3 in testicular activities in adult mice
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DOI：
10.1530/joe-14-0333
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发表时间：
2014-10-01
影响因子：
4
通讯作者：
Tsutsui, Kazuyoshi
中科院分区：
文献类型：
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作者：
Anjum, Shabana;Krishna, Amitabh;Tsutsui, Kazuyoshi
本研究的目的是评价哺乳动物促性腺激素抑制激素同源物雷法米德相关肽3(RFRP3)在体内和体外对小鼠睾丸活动(精子发生和类固醇生成)的影响。给小鼠体内注射不同剂量的RFRP3(对照组：0.02、0.2、2.0 mg/d)，连续8天。在体外实验中，用不同剂量的RFRP3(对照组：1和10 ng/ml)与或不加黄体生成素(对照组：10和100 ng/ml)在37℃条件下作用24 h，观察RFRP3对小鼠体质量、循环类固醇水平和睾丸活力的影响。RFRP3治疗还引起精子发生的剂量依赖性组织学改变，如生殖细胞增殖和存活标志物下降，睾丸中凋亡标志物增加。体内和体外研究均表明，RFRP3对睾丸睾酮合成有抑制作用。RFRP3能抑制睾丸组织黄体生成素受体(LHCGR)、STAR蛋白、细胞色素P450侧链裂解酶(Cyp11a1)和3β-羟基类固醇脱氢酶的表达，并呈剂量依赖性。本研究还提示，RFRP3在睾丸中的抑制作用可能是通过局部产生GnRH来实现的。因此，RFRP3通过GnRH间接或通过直接影响生殖细胞的增殖、存活和凋亡来抑制睾丸类固醇激素的发生和精子的发生。
The aim of this study was to evaluate the effects of in vivo and in vitro treatments with RFamide-related peptide 3 (RFRP3), a mammalian gonadotropin-inhibitory hormone ortholog, on testicular activities, i.e. spermatogenesis and steroidogenesis, in mice. Mice were treated in vivo with different doses of RFRP3 (control: 0.02 mu g, 0.2 mu g, and 2.0 mu g/day) for 8 days. For in vitro study, the testes of mice were evaluated with different doses of RFRP3 (control: 1 and 10 ng/ml) with or without LH (control: 10 and 100 ng/ml) for 24 h at 37 degrees C. RFRP3 treatment produced significant changes in the body mass, circulating steroid level, and testicular activity in mice. RFRP3 treatment also caused dose-dependent histological changes in spermatogenesis, such as decline in germ cell proliferation and survival markers and increase in apoptotic markers in testis. Both in vivo and in vitro studies showed the inhibitory effect of RFRP3 on testosterone synthesis in the testis. RFRP3 inhibited the expression of the receptor for LH (LHCGR), STAR protein, cytochrome P450 side-chain cleavage (CYP11A1) and 3 beta-hydroxysteroid dehydrogenase in the testis, and testosterone secretion dose dependently. This study also suggested that the inhibitory effect of RFRP3 in the testis may be mediated through local production of GnRH. Thus, RFRP3 inhibits testicular steroidogenesis and spermatogenesis either indirectly through GnRH or by directly influencing germ cell proliferation, survival, and apoptosis.