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人重组生长激素对离体人阴茎勃起组织作用的潜在机制。

Potential mechanism of action of human growth hormone on isolated human penile erectile tissue.

机构信息

Department of Urology and Uro-Oncology, Hannover Medical School, Hannover, Germany.

出版信息

Urology. 2010 Apr;75(4):968-73. doi: 10.1016/j.urology.2009.05.046. Epub 2009 Jul 22.

Abstract

OBJECTIVES

To evaluate the mechanisms of growth hormone (GH) action on isolated human penile erectile tissue. Human GH (hGH) has been suggested to play a role in male reproductive function, including penile erection. Nevertheless, it still remains unclear which intracellular pathways mediate the physiological effects of GH on the human corpus cavernosum (HCC).

METHODS

Using the organ bath technique, the effects of GH were investigated on electrical field stimulation (EFS)-induced relaxation of isolated HCC in the absence and presence of the guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and nitric oxide synthase (NOS) inhibitor N(G)-nitro-l-arginine (l-NOARG, 10 microm). Effects of GH on the production of tissue cyclic guanosine monophosphate (cGMP) in the absence and presence of ODQ and l-NOARG were also elucidated using radioimmunoassay.

RESULTS

ODQ and l-NOARG abolished the relaxation of the tissue induced by EFS, whereas amplitudes were increased by physiological concentrations of GH (1-100 nm). The attenuation of EFS-induced amplitudes by l-NOARG but not ODQ was, in part, reversed by GH. The production of cGMP (pmol cGMP/mg protein) induced by 10 nm GH was abolished in the presence of 10 microm ODQ. In contrast, the combination of GH (10 nm) and l-NOARG (10 microm) maintained cGMP production significantly greater than baseline (0.68 +/- 0.36 vs 1.07 +/- 0.48 pmol cGMP/mg protein).

CONCLUSIONS

Our data provide evidence that GH may act on human HCC by an NO-independent effect on guanylyl cyclase activity and may thus explain how growth factors, such as hGH, regulate male erectile function.

摘要

目的

评估生长激素(GH)对离体人阴茎勃起组织作用的机制。生长激素(hGH)被认为在男性生殖功能中发挥作用,包括阴茎勃起。然而,GH 对人海绵体(HCC)的生理作用是通过何种细胞内途径介导仍不清楚。

方法

使用器官浴技术,研究 GH 对无及存在鸟苷酸环化酶抑制剂 1H-[1,2,4]恶二唑[4,3-a]喹喔啉-1-酮(ODQ)和一氧化氮合酶(NOS)抑制剂 N(G)-硝基-L-精氨酸(l-NOARG,10 μm)时,电刺激(EFS)诱导的离体 HCC 松弛的影响。还使用放射免疫测定法阐明了 GH 对组织中环鸟苷酸(cGMP)产生的影响,以及在存在 ODQ 和 l-NOARG 时的影响。

结果

ODQ 和 l-NOARG 消除了 EFS 诱导的组织松弛,而生理浓度的 GH(1-100 nm)则增加了松弛幅度。l-NOARG 而非 ODQ 对 EFS 诱导幅度的衰减部分被 GH 逆转。10nm GH 诱导的 cGMP(pmol cGMP/mg 蛋白)产生在 10μm ODQ 存在时被消除。相反,GH(10nm)和 l-NOARG(10μm)的组合使 cGMP 产生保持显著高于基线(0.68±0.36 对 1.07±0.48 pmol cGMP/mg 蛋白)。

结论

我们的数据提供了证据,表明 GH 可能通过对鸟苷酸环化酶活性的非 NO 依赖作用作用于人 HCC,从而解释了生长因子(如 hGH)如何调节男性勃起功能。

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