MECHANISM OF ACTION OF PEPTIDE HORMONES IN STEROIDOGENIC CELLS

促性腺激素是睾丸间质细胞和支持细胞的主要支持物 睾丸功能和最突出的局部调节激素 睾丸激素是睾丸间质细胞合成的， 作为生殖细胞发育的主要旁分泌刺激物。许多 另外的局部调节物质作为自分泌调节剂， 介导不同睾丸内的旁分泌相互作用 隔间这些包括生长因子，几种神经肽， 促肾上腺皮质激素释放激素（CRF）， 阿片类药物和胺如血清素。皮质激素释放激素 因子是应激级联反应中的关键神经肽， 除了已知的抗生殖作用外， 中枢水平的影响（性行为和LH抑制） 分泌）。培养的间质细胞能够产生下丘脑 释放激素，如CRF，通过不同的高- 亲和受体作为间质细胞负性自分泌调节因子 通过抑制促性腺激素刺激的cAMP生成发挥作用， 类固醇生成刺激间质细胞分泌CRF 通过LH，通过5-羟色胺（5-HT）的释放和自分泌激活 不同于脑部位的5 HT 2受体（DOI，5 HT 2部位的激动剂 在大脑中，作为高亲和力位点的拮抗剂， Leydig细胞中低亲和力位点的激动剂）。普萘洛尔 原型β-肾上腺素能阻滞剂经常用于控制 高血压患者的血压，往往与 阳痿，通过睾丸激素能机制作用于睾丸间质细胞， 刺激CRF分泌并引起LH诱导cAMP的显著抑制 生产和类固醇生成。普萘洛尔，作为一种拮抗剂， Leydig细胞低亲和力受体位点（具有 自动受体），促进血清素的释放，血清素反过来又起作用 通过高亲和力位点刺激CRF释放。这种过敏性 药物的作用可能导致性功能的损害 普萘洛尔治疗期间报告。其他研究表明， 另一种神经肽激素，生长激素释放激素（GHRH）， 存在于睾丸间质细胞中该肽主动地从 细胞培养，是在促性腺激素的控制下，并通过VIP的行为， 受体作为间质细胞功能的直接刺激物/或促进物 LH诱导的cAMP产生和类固醇生成。由于GHRH也是一个 刺激基础和FSH刺激的支持细胞功能， 得出结论，睾丸GHRH是自分泌/旁分泌阳性 男性性腺功能的调节器。分泌和作用改变 睾丸GHRH可能参与某些雄激素紊乱 生产和某些形式的男性特发性不育。

Gonadotropins are the primary support for Leydig and Sertoli cell function and the most prominent local regulatory hormone of testicular function is testosterone, which is synthesized by the Leydig cells and acts as the major paracrine stimulator of germ cell development. Many additional local regulatory substances act as autocrine modulators and mediate paracrine interactions between the different intratesticular compartments. These include growth factors, several neuropeptides such as GnRH and most importantly, corticotropin releasing hormone (CRF) and opioids, and amines such as serotonin. Corticotropin-releasing hormone factor, the key neuropeptide in the stress cascade, has major inhibitory actions on testicular function in addition to its known antireproductive effects at the central level (inhibition of sexual behavior and LH secretion). Leydig cells in culture are able to produce hypothalamic releasing hormones such as CRF, which acts through distinct high- affinity receptors as a negative autocrine regulator of Leydig cell function by inhibiting gonadotropin-stimulated cAMP generation and steroidogenesis. The secretion of CRF by the Leydig cell is stimulated by LH, acting via release of serotonin (5HT) and autocrine activation of 5HT2 receptors distinct from brain sites (DOI, an agonist for 5HT2 sites in the brain, acts as an antagonist of the high-affinity sites and an agonist to the low-affinity sit in the Leydig cell). Propranolol, the prototype beta-adrenergic blocker frequently used in the control of blood pressure in patients with hypertension, and often associated with impotence, acts in the Leydig cell via serotonergic mechanism to stimulate CRF secretion and causes marked inhibition of LH-induced cAMP production and steroidogenesis. Propranolol, acting as an antagonist of the Leydig cell low-affinity receptor sites (with properties of autoreceptors), promotes the release of serotonin which in turn acts through high-affinity sites to stimulate CRF release. This serotonergic action of the drug could contribute to the impairment of sexual function reported during propranolol treatment. Other studies revealed that another neuropeptide hormone, growth hormone releasing hormone (GHRH), is present in the Leydig cell. The peptide is actively released from cells in culture, is under gonadotropin control, and acts via a VIP receptor as a direct stimulator of Leydig cell function/or facilitator of LH-induced cAMP production and steroidogenesis. Since GHRH is also a stimulus of basal and FSH-stimulated Sertoli cell function, it is concluded that testicular GHRH is an autocrine/paracrine positive regulator of male gonadal function. Altered secretion and actions of testicular GHRH may be involved in certain disorders of androgen production and some forms of male idiopathic infertility.