Department of Biomedical, Metabolic, and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
Center for Genomic Research, University of Modena and Reggio Emilia, Modena, Italy.
Endocr Rev. 2018 Oct 1;39(5):549-592. doi: 10.1210/er.2018-00065.
LH and chorionic gonadotropin (CG) are glycoproteins fundamental to sexual development and reproduction. Because they act on the same receptor (LHCGR), the general consensus has been that LH and human CG (hCG) are equivalent. However, separate evolution of LHβ and hCGβ subunits occurred in primates, resulting in two molecules sharing ~85% identity and regulating different physiological events. Pituitary, pulsatile LH production results in an ~90-minute half-life molecule targeting the gonads to regulate gametogenesis and androgen synthesis. Trophoblast hCG, the "pregnancy hormone," exists in several isoforms and glycosylation variants with long half-lives (hours) and angiogenic potential and acts on luteinized ovarian cells as progestational. The different molecular features of LH and hCG lead to hormone-specific LHCGR binding and intracellular signaling cascades. In ovarian cells, LH action is preferentially exerted through kinases, phosphorylated extracellular-regulated kinase 1/2 (pERK1/2) and phosphorylated AKT (also known as protein kinase B), resulting in irreplaceable proliferative/antiapoptotic signals and partial agonism on progesterone production in vitro. In contrast, hCG displays notable cAMP/protein kinase A (PKA)-mediated steroidogenic and proapoptotic potential, which is masked by estrogen action in vivo. In vitro data have been confirmed by a large data set from assisted reproduction, because the steroidogenic potential of hCG positively affects the number of retrieved oocytes, and LH affects the pregnancy rate (per oocyte number). Leydig cell in vitro exposure to hCG results in qualitatively similar cAMP/PKA and pERK1/2 activation compared with LH and testosterone. The supposed equivalence of LH and hCG has been disproved by such data, highlighting their sex-specific functions and thus deeming it an oversight caused by incomplete understanding of clinical data.
LH 和绒毛膜促性腺激素（CG）是对性发育和生殖至关重要的糖蛋白。由于它们作用于相同的受体（LHCGR），因此普遍认为 LH 和人绒毛膜促性腺激素（hCG）是等同的。然而，在灵长类动物中，LHβ和 hCGβ亚基分别进化，导致这两种分子具有约 85%的同源性，并调节不同的生理事件。垂体脉冲式 LH 产生导致半衰期约为 90 分钟的分子靶向性腺，以调节配子发生和雄激素合成。滋养层 hCG，即“妊娠激素”，存在几种同工型和糖基化变体，半衰期较长（数小时），具有血管生成潜能，并在黄体化的卵巢细胞中作为孕激素发挥作用。LH 和 hCG 的不同分子特征导致激素特异性 LHCGR 结合和细胞内信号级联反应。在卵巢细胞中，LH 作用主要通过激酶、磷酸化细胞外调节激酶 1/2（pERK1/2）和磷酸化 AKT（也称为蛋白激酶 B）发挥作用，导致不可替代的增殖/抗凋亡信号和体外孕激素产生的部分激动作用。相比之下，hCG 表现出明显的 cAMP/蛋白激酶 A（PKA）介导的甾体生成和促凋亡潜能，但在体内被雌激素作用掩盖。大量辅助生殖数据证实了体外数据，因为 hCG 的甾体生成潜能对取回的卵母细胞数量有积极影响，而 LH 则影响妊娠率（每个卵母细胞数）。与 LH 和睾酮相比，体外暴露于 hCG 的间质细胞导致 cAMP/PKA 和 pERK1/2 激活具有定性相似性。这些数据证明了 LH 和 hCG 的等效性是不正确的，突出了它们的性别特异性功能，因此认为这是对临床数据理解不完整造成的疏忽。
