Angiotensin II regulates testicular peritubular cell function via AT1 receptor: A specific situation in male infertility

Angiotensin II regulates testicular peritubular cell function via AT1 receptor: A specific situation in male infertility
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血管紧张素II通过AT1受体调节睾丸管周细胞功能:男性不育的特殊情况

DOI:
10.1016/j.mce.2014.06.011
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发表时间:
2014
影响因子:
4.1
通讯作者:
Mayerhofer A
Mayerhofer A
中科院分区:
医学2区
文献类型:
--
作者:
Welter H;Huber A;Lauf S;Einwang D;Mayer C;Schwarzer JU;Köhn FM;Mayerhofer A

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我们观察到人睾丸小管周围肌样细胞对血管紧张素II (AngII)受体(AT1R)具有免疫反应性,并探讨了AngII在培养的人睾丸小管周围细胞(HTPCs)中的作用。作为对AngII的回应,它们在几分钟内就收缩了。AT1R阻滞剂氯沙坦阻断收缩,暗示AngII和AT1R参与睾丸内精子运输。AngII还在数小时内显著增加IL-6 mRNA水平和IL-6分泌,氯沙坦再次阻止了这一作用。这表明参与了炎症过程,这可能在男性不育中起作用。AngII可由肥大细胞(MC)衍生的切酶(CHY)在局部产生,切酶可裂解AngI。在不育男性的睾丸活检中,我们发现在精管壁内有大量表达CHY的MCs。相比之下,chy阳性MCs在正常人类睾丸中很少发现。睾丸炎症事件可能导致精子发生受损。因此,对MCs、CHY或AT1R进行干预治疗可能是治疗男性不育症的新选择。
We observed that peritubular myoid cells in the human testis are immunoreactive for angiotensin II (AngII) receptors (AT1R) and explored AngII actions in cultured human testicular peritubular cells (HTPCs). In response to AngII they contracted within minutes. The AT1R-blocker losartan blocked contraction, implying involvement of AngII and AT1R in intratesticular sperm transport. AngII also significantly increased IL-6 mRNA levels and IL-6 secretion within hours and losartan again prevented this action. This suggests involvement in inflammatory processes, which may play a role in male infertility. AngII can be generated locally by mast cell (MC)-derived chymase (CHY), which cleaves AngI. In testicular biopsies from infertile men we found abundant MCs, which express CHY, within the wall of seminiferous tubules. In contrast, CHY-positive MCs are hardly found in normal human testis. Testicular inflammatory events may fuel processes resulting in impaired spermatogenesis. Therefore therapeutic interference with MCs, CHY or AT1R might be novel options in male infertility.
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