Kotzmann H, Riedl M, Clodi M, Barnas U, Kaider A, Höcker P, Luger A
Department of Medicine III, University of Vienna, Austria.
Eur J Clin Invest. 1996 Dec;26(12):1175-81. doi: 10.1046/j.1365-2362.1996.690604.x.
It has been reported that hypophysectomized rats exhibit normochromic, normocytic anaemia. Pancytopenia with impaired DNA synthesis in the bone marrow can be restored in these hypophysectomized rats by syngeneic pituitary grafts placed under the kidney capsule or treatment with growth hormone (GH). Until now, adults with hypopituitarism have received adequate replacement therapy with thyroxine, cortisol and sex steroids, but not with GH. We therefore investigated the effects of GH replacement therapy on the proliferation and differentiation of erythroid and myeloid progenitor and peripheral blood cells in 11 adult patients with growth hormone deficiency in a double-blind, placebo-controlled study for the first 6 months of therapy. The placebo group showed no changes during the first 6 months without therapy in either insulin-like growth factor I (IGF-I) levels, erythroid and myeloid progenitor precursor cells or peripheral blood cells. After commencement of GH therapy, IGF-I levels rose significantly during 24 months of therapy from 75.3 +/- 13.5 to 225 +/- 34.7 ng mL-1 (P < 0.001). Erythroid and myeloid progenitor precursor cells showed a steep and significant increase after 18 and 24 months of therapy (erythroid: from 10.7 +/- 3.5 to 261.4 +/- 79.8, P < 0.02, after 18 months and to 276.8 +/- 149.8 x 10(5) mononuclear cell colonies, P < 0.03, after 24 months; granulocyte-macrophage colony-forming units: from 39.7 +/- 9.8 to 316.9 +/- 124.6, P < 0.002, after 18 months and to 366 +/- 188.7 x 10(5) mononuclear cell colonies, P < 0.03, after 24 months), whereas the peripheral red and white blood cells exhibited only minimal non-significant changes. The principal regulators of erythropoiesis, such as erythropoietin, and parameters reflecting erythropoiesis in the peripheral blood, such as reticulocytes, remained almost unchanged throughout the whole study period. We therefore conclude that patients with GH deficiency do not have anaemia, but have haematopoietic precursor cells in the lower normal range, and that GH substitution therapy over a period of 24 months has a marked effect on erythroid and myeloid progenitor precursor cells but only negligible effects on peripheral blood cells in GH-deficient adults.
据报道,垂体切除的大鼠表现出正色素性、正细胞性贫血。骨髓中DNA合成受损的全血细胞减少症,可通过置于肾包膜下的同基因垂体移植或生长激素(GH)治疗在这些垂体切除的大鼠中得到恢复。到目前为止,垂体功能减退的成年人已接受了甲状腺素、皮质醇和性类固醇的充分替代治疗,但未接受GH治疗。因此,我们在一项双盲、安慰剂对照研究中,对11名生长激素缺乏的成年患者进行了为期6个月的治疗,调查了GH替代治疗对红系和髓系祖细胞及外周血细胞增殖和分化的影响。安慰剂组在最初6个月未治疗期间,胰岛素样生长因子I(IGF-I)水平、红系和髓系祖细胞前体细胞或外周血细胞均无变化。开始GH治疗后,治疗24个月期间IGF-I水平显著升高,从75.3±13.5 ng/mL升至225±34.7 ng/mL(P<0.001)。治疗18个月和24个月后,红系和髓系祖细胞前体细胞显著急剧增加(红系:18个月后从10.7±3.5增至261.4±79.8,P<0.02,24个月后增至276.8±149.8×10⁵个单核细胞集落,P<0.03;粒细胞-巨噬细胞集落形成单位:18个月后从39.7±9.8增至316.9±124.6,P<0.002,24个月后增至366±188.7×10⁵个单核细胞集落,P<0.03),而外周红细胞和白细胞仅表现出微小的、无统计学意义的变化。整个研究期间,红细胞生成的主要调节因子,如促红细胞生成素,以及反映外周血红细胞生成的参数,如网织红细胞,几乎保持不变。因此我们得出结论,生长激素缺乏的患者没有贫血,但造血前体细胞处于正常范围下限,并且24个月的生长激素替代治疗对生长激素缺乏的成年人的红系和髓系祖细胞前体细胞有显著影响,但对外周血细胞的影响可忽略不计。