Markham K E, Kaye P L
School of Biomedical Sciences, The University of Queensland, Brisbane, QLD 4072, Australia.
Reproduction. 2003 Mar;125(3):327-36. doi: 10.1530/rep.0.1250327.
The role of growth hormone (GH) in embryonic growth is controversial, yet preimplantation embryos express GH, insulin-like growth factor I (IGF-I) and their receptors. In this study, addition of bovine GH doubled the proportion of two-cell embryos forming blastocysts and increased by about 25% the number of cells in those blastocysts with a concentration-response curve showing maximal activity at 1 pg bovine GH ml(-1), with decreasing activity at higher and lower concentrations. GH increased the number of cells in the trophectoderm by 25%, but did not affect the inner cell mass of blastocysts. Inhibition of cell proliferation by anti-GH antiserum indicated that GH is a potent autocrine or paracrine regulator of the number of trophectoderm cells in vivo. Type 1 IGF receptors (IGF1R) were localized to cytoplasmic vesicles and plasma membrane in the apical domains of uncompacted and compacted eight-cell embryos, but were predominantly apparent in cytoplasmic vesicles of the trophectoderm cells of the blastocyst, similar to GH receptors. Studies using alpha IR3 antiserum which blocks ligand activation of IGF1R, showed that IGF1R participate in the autocrine or paracrine regulation of the number of cells in the inner cell mass by an endogenous IGF-I-IGF1R pathway. However, alpha IR3 did not affect GH stimulation of the number of trophectoderm cells. Therefore, GH does not use secondary actions via embryonic IGF-I to modify the number of blastocyst cells. This result indicates that GH and IGF-I act independently. GH may selectively regulate the number of trophectoderm cells and thus implantation and placental growth. Embryonic GH may act in concert with IGF-I, which stimulates proliferation in the inner cell mass, to optimize blastocyst development.
生长激素（GH）在胚胎生长中的作用存在争议，然而植入前胚胎可表达GH、胰岛素样生长因子I（IGF-I）及其受体。在本研究中，添加牛GH使形成囊胚的二细胞胚胎比例增加了一倍，并使那些囊胚中的细胞数量增加了约25%，浓度-反应曲线显示在1 pg牛GH ml(-1)时活性最大，在更高和更低浓度时活性降低。GH使滋养外胚层中的细胞数量增加了25%，但不影响囊胚的内细胞团。抗GH抗血清对细胞增殖的抑制表明，GH在体内是滋养外胚层细胞数量的有效自分泌或旁分泌调节因子。1型IGF受体（IGF1R）定位于未致密化和致密化的八细胞胚胎顶端区域的细胞质囊泡和质膜中，但主要出现在囊胚滋养外胚层细胞的细胞质囊泡中，类似于GH受体。使用阻断IGF1R配体激活的α IR3抗血清的研究表明，IGF1R通过内源性IGF-I-IGF1R途径参与内细胞团细胞数量的自分泌或旁分泌调节。然而，α IR3并不影响GH对滋养外胚层细胞数量的刺激。因此，GH不通过胚胎IGF-I的次级作用来改变囊胚细胞数量。这一结果表明GH和IGF-I独立发挥作用。GH可能选择性地调节滋养外胚层细胞数量，从而影响着床和胎盘生长。胚胎GH可能与刺激内细胞团增殖的IGF-I协同作用，以优化囊胚发育。
