Department of Cytology, Histology & Embryology B, Faculty of Medicine, University of La Plata, Argentina.
Life Sci. 2012 Sep 4;91(5-6):166-71. doi: 10.1016/j.lfs.2012.06.037. Epub 2012 Jul 8.
There is clear evidence for the existence of a bi-directional thymus-somatotropic axis and several studies suggest that the thymic peptide thymulin may be involved in this communication. We undertook to assess the impact of serum thymulin immunoneutralization in C57BL/6 mice and that of neonatal thymulin gene therapy (NTGT) in nude mice on body weight (BW) gain and on the histomorphometric profile of the somatotrope population.
Immunoneutralization of thymulin was done from postnatal day 1 to 35 by i.p. injections of rabbit anti-thymulin serum (α-FTS) and normal rabbit serum (NRS) in controls. NTGT was implemented in nudes using an adenoviral vector expressing a synthetic gene for thymulin (RAd-FTS). On postnatal day 1, heterozygous (nu/+) and homozygous (nu/nu) pups received a single bilateral i.m. injection either RAd-FTS or RAd-GFP (a control vector expressing green fluorescent protein). BW gain was recorded and at the end of the study the pituitaries were immunostained for growth hormone (GH). Serum GH and thymulin were determined by radioimmunoassay and bioassay, respectively.
Thymulin immunoneutralization induced a significant decrease in BW gain, serum GH and somatotrope cell density as well as an increase in somatotrope cell size. NTGT markedly increased BW gain, serum thymulin (P<0.01) and somatotrope cell and volume density in nu/nu mice.
Our results suggest that thymulin plays a relevant physiological role on the thymus-somatotropic axis in mice.
胸腺-生长激素轴的双向性已得到明确证实,并且有多项研究表明胸腺肽胸腺素可能参与这种交流。我们着手评估在 C57BL/6 小鼠中进行血清胸腺素免疫中和以及在裸鼠中进行新生胸腺素基因治疗(NTGT)对体重(BW)增加和生长激素细胞群体的组织形态学特征的影响。
从出生后第 1 天到第 35 天,通过腹腔内注射兔抗胸腺素血清(α-FTS)和对照用正常兔血清(NRS)对胸腺素进行免疫中和。在裸鼠中,使用表达合成胸腺素基因的腺病毒载体(RAd-FTS)进行 NTGT。在出生后第 1 天,杂合子(nu/+)和纯合子(nu/nu)幼崽接受了单侧双侧肌肉注射 RAd-FTS 或 RAd-GFP(表达绿色荧光蛋白的对照载体)。记录 BW 增加,并在研究结束时对垂体进行生长激素(GH)免疫染色。通过放射免疫测定法和生物测定法分别测定血清 GH 和胸腺素。
胸腺素免疫中和导致 BW 增加、血清 GH 和生长激素细胞密度显著减少,以及生长激素细胞大小增加。NTGT 显著增加了 nu/nu 小鼠的 BW 增加、血清胸腺素(P<0.01)以及生长激素细胞和体积密度。
我们的结果表明,胸腺素在小鼠的胸腺-生长激素轴中发挥相关的生理作用。