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男性生殖功能的神经内分泌控制。阿片系统作为多部位控制的模型。

Neuroendocrine control of male reproductive function. The opioid system as a model of control at multiple sites.

作者信息

Fabbri A, Jannini E A, Gnessi L, Ulisse S, Moretti C, Isidori A

机构信息

Chair of Andrology, University of Rome La Sapienza, Italy.

出版信息

J Steroid Biochem. 1989 Jan;32(1B):145-50. doi: 10.1016/0022-4731(89)90155-6.

DOI:10.1016/0022-4731(89)90155-6
PMID:2643737
Abstract

It is known that the same peptide can be identified in different secretory tissues and in the central nervous system (CNS). We now provide evidence that the same peptides can be found in different organs related to the control of a single function, and speculate on the possibility that this reflects a common neuroendocrine programming. Endogenous opioid peptides (EOP) inhibit the reproductive function acting via the CNS. EOP inhibit gonadotropin secretion in rodents and humans via inhibition of GnRH release and have direct inhibitory actions at the pituitary level via specific binding sites on the gonadotrophs. However, EOP can also be synthesized in the testis and in different compartments of the male genital tract. Several findings indicate that EOP of the reproductive tract have a local, paracrine role. These include: (1) the detection of significant beta-endorphin (beta-EP) production by rat Leydig cells (Lc) in cultures; (2) the hormonal regulation of Lc beta-EP production by positive (gonadotropins) and negative (steroids, glucocorticoids, GnRH) factors; (3) the presence of opioid binding sites (Kd in the nanomolar range) in tubular homogenates and Sertoli cells (Sc) in culture of adult and immature rat testes; (4) the inhibition of basal and FSH-stimulated ABP production by Sc in culture when chronically exposed to beta-EP treatment; (5) the detection of high levels of beta-EP and met-enkephalin in human semen with values 6-12 times higher than in plasma; (6) the evidence for inhibitory functions of seminal opioids on sperm motility, vas deferens muscle contraction and partner immune system. Thus the same peptides, i.e. EOP, may control the reproductive function at multiple sites, operating as a multimessenger system in which the central and peripheral level are unified by the common chemical and inhibitory nature of the message.

摘要

众所周知,同一肽段可在不同分泌组织及中枢神经系统(CNS)中被鉴定出来。我们现在提供证据表明,同一肽段可在与单一功能控制相关的不同器官中被发现,并推测这可能反映了一种共同的神经内分泌编程。内源性阿片肽(EOP)通过中枢神经系统抑制生殖功能。EOP通过抑制GnRH释放来抑制啮齿动物和人类的促性腺激素分泌,并通过促性腺细胞上的特异性结合位点在垂体水平发挥直接抑制作用。然而,EOP也可在睾丸及雄性生殖道的不同区域合成。多项研究结果表明,生殖道中的EOP具有局部旁分泌作用。这些包括:(1)在培养的大鼠睾丸间质细胞(Lc)中检测到显著的β-内啡肽(β-EP)产生;(2)促性腺激素(阳性)和类固醇、糖皮质激素、GnRH(阴性)因子对Lcβ-EP产生的激素调节;(3)成年和未成年大鼠睾丸培养物中,管状匀浆和支持细胞(Sc)中存在纳摩尔范围内的阿片类结合位点(Kd);(4)长期暴露于β-EP处理时,培养的Sc对基础及FSH刺激的ABP产生的抑制作用;(5)在人类精液中检测到高水平的β-EP和甲硫氨酸脑啡肽,其值比血浆中高6 - 12倍;(6)精液阿片类物质对精子活力、输精管肌肉收缩及伴侣免疫系统具有抑制作用的证据。因此,同一肽段,即EOP,可能在多个位点控制生殖功能,作为一种多信使系统发挥作用,其中中枢和外周水平通过信息的共同化学性质和抑制性质而统一。

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