Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire, Clifford Bridge Road, Coventry CV2 2DX, UK.
Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV2 2DX, UK.
Int J Mol Sci. 2021 Jul 30;22(15):8217. doi: 10.3390/ijms22158217.
Reproductive function depends upon an operational hypothalamo-pituitary-gonadal (HPG) axis. Due to its role in determining survival versus reproductive strategies, the HPG axis is vulnerable to a diverse plethora of signals that ultimately manifest with Central Hypogonadism (CH) in all its many guises. Acquired CH can result from any pituitary or hypothalamic lesion, including its treatment (such as surgical resection and/or radiotherapy). The HPG axis is particularly sensitive to the suppressive effects of hyperprolactinaemia that can occur for many reasons, including prolactinomas, and as a side effect of certain drug therapies. Physiologically, prolactin (combined with the suppressive effects of autonomic neural signals from suckling) plays a key role in suppressing the gonadal axis and establishing temporary CH during lactation. Leptin is a further key endocrine regulator of the HPG axis. During starvation, hypoleptinaemia (from diminished fat stores) results in activation of hypothalamic agouti-related peptide neurons that have a dual purpose to enhance appetite (important for survival) and concomitantly suppresses GnRH neurons via effects on neural kisspeptin release. Obesity is associated with hyperleptinaemia and leptin resistance that may also suppress the HPG axis. The suppressibility of the HPG axis also leaves it vulnerable to the effects of external signals that include morphine, anabolic-androgenic steroids, physical trauma and stress, all of which are relatively common causes of CH. Finally, the HPG axis is susceptible to congenital malformations, with reports of mutations within >50 genes that manifest with congenital CH, including Kallmann Syndrome associated with hyposmia or anosmia (reduction or loss of the sense of smell due to the closely associated migration of GnRH with olfactory neurons during embryogenesis). Analogous to the HPG axis itself, patients with CH are often vulnerable, and their clinical management requires both sensitivity and empathy.
生殖功能依赖于下丘脑-垂体-性腺（HPG）轴的正常运作。由于其在决定生存或生殖策略方面的作用，HPG 轴容易受到多种信号的影响，最终导致各种形式的中枢性性腺功能减退症（CH）。获得性 CH 可由任何垂体或下丘脑病变引起，包括其治疗（如手术切除和/或放疗）。HPG 轴对高催乳素血症的抑制作用特别敏感，高催乳素血症可由多种原因引起，包括催乳素瘤，以及某些药物治疗的副作用。在生理上，催乳素（与哺乳时自主神经信号的抑制作用相结合）在抑制性腺轴和在哺乳期建立暂时的 CH 方面发挥着关键作用。瘦素是 HPG 轴的另一个关键内分泌调节剂。在饥饿状态下，瘦素水平降低（由于脂肪储存减少）会导致下丘脑 AgRP 神经元被激活，这些神经元具有双重作用，一方面增强食欲（对生存很重要），另一方面通过影响神经肽 Kiss1 的释放来抑制 GnRH 神经元。肥胖与高瘦素血症和瘦素抵抗有关，也可能抑制 HPG 轴。HPG 轴的抑制作用使其容易受到外部信号的影响，包括吗啡、合成代谢雄激素类固醇、物理创伤和应激，所有这些都是 CH 的相对常见原因。最后，HPG 轴容易受到先天性畸形的影响，据报道，超过 50 种基因突变会导致先天性 CH，包括与嗅觉减退或嗅觉丧失（由于 GnRH 在胚胎发生期间与嗅觉神经元的密切迁移而导致嗅觉丧失）相关的 Kallmann 综合征。类似于 HPG 轴本身，CH 患者通常很脆弱，他们的临床管理需要敏感性和同理心。
