Testosterone and estrogen concentrations progressively increase during puberty, and in association with growth hormone (GH), lead to the increase in height velocity known as the pubertal growth spurt. Very limited information is available however, regarding the possible effects of sex steroids over GH cellular sensitivity.

Objective

To investigate the effects of different concentrations of testosterone, estradiol and dihydrotestosterone over the GH intracellular signaling pathway.

Methods

We evaluated the effects of these sex steroids on the nuclear phosphorylation of STAT5b and IGF-1 expression, in HEPG2 human hepatoma cells. In addition, we studied whether Tamoxifen (TAM), can modulate these effects.

Results

The highest concentration of T tested (10 ng/mL) co-incubated with a fixed concentration of GH (40 ng/mL) increased nuclear STAT5b phosphorylation compared with GH alone (1.34 ± 0.2 vs 0.6 ± 0.09 AU; *p < 0.05), as well as IGF-1 expression (0.6 ± 0.03 vs 0.32 ± 0.05 AU; *p < 0.05). This effect was not observed with lower concentrations of T tested (1 and 5 ng/mL). A similar increase in nuclear STAT5b phosphorylation was observed with the lowest concentration of E₂ tested (20 pg/mL), co-incubated with the same fixed concentration of GH (3.6 ± 0.5 vs 1.28 ± 0.33 AU; *p < 0.05). This effect was also associated with an increase in IGF-1 expression (0.73 ± 0.02 vs 0.39 ± 0.04 AU; *p < 0.05). These results were not observed with higher concentrations of E₂ tested (75 and 200 pg/mL). DHT at concentrations of 0.1, 0.25 and 0.5 ng/mL, co-stimulated with GH, did not change cytoplasmic STAT5b phosphorylation, nuclear STAT5b or IGF-1 expression. In addition, the co-incubation of TAM with the highest concentration of T tested (10 ng/mL) and GH (40 ng/mL) did not change cytoplasmic, nuclear pSTAT5 levels or IGF-1 expression.

Conclusions

T and E₂ potentiate the GH signaling pathway in a concentration-dependent fashion. The observation that the non-aromatizable androgen dihydrotestosterone does not stimulate this pathway, and that the effects of T are blocked with TAM, suggests that the effects of T over the GH signaling pathway appear to be mediated by estrogen.

中文翻译：

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雄激素和雌激素对 HEPG2 细胞中细胞 GH 敏感性的不同影响

睾酮和雌激素浓度在青春期逐渐增加，并且与生长激素 (GH) 相关，导致身高速度增加，称为青春期生长突增。然而，关于性类固醇对 GH 细胞敏感性的可能影响，可获得的信息非常有限。

客观的

研究不同浓度的睾酮、雌二醇和二氢睾酮对 GH 细胞内信号通路的影响。

方法

我们评估了这些性类固醇对 HEPG2 人肝癌细胞中 STAT5b 和IGF-1表达的核磷酸化的影响。此外，我们研究了他莫昔芬 (TAM) 是否可以调节这些作用。

结果

与单独的 GH 相比，最高浓度的 T 测试 (10 ng/mL) 与固定浓度的 GH (40 ng/mL) 共孵育增加了核 STAT5b 磷酸化 (1.34 ± 0.2 vs 0.6 ± 0.09 AU; * p  < 0.05) ，以及IGF-1表达（0.6 ± 0.03 vs 0.32 ± 0.05 AU；*p < 0.05）。用较低浓度的 T 测试 (1 和 5 ng/mL) 没有观察到这种效果。_{用最低浓度的 E 2}测试 (20 pg/mL)观察到核 STAT5b 磷酸化的类似增加，与相同固定浓度的 GH 共同孵育 (3.6 ± 0.5 vs 1.28 ± 0.33 AU；* p  < 0.05)。这种效应还与IGF-1表达的增加有关（0.73 ± 0.02 vs 0.39 ± 0.04 AU；* p < 0.05)。_{用较高浓度的 E 2}测试（75 和 200 pg/mL）未观察到这些结果。浓度为 0.1、0.25 和 0.5 ng/mL 的 DHT，与 GH 共同刺激，不会改变细胞质 STAT5b 磷酸化、核 STAT5b 或IGF-1表达。此外，TAM 与最高浓度的 T (10 ng/mL) 和 GH (40 ng/mL) 共孵育不会改变细胞质、核 pSTAT5 水平或IGF-1表达。

结论

T 和 E ₂以浓度依赖性方式增强 GH 信号通路。观察到不可芳香化的雄激素二氢睾酮不刺激该途径，并且 TAM 的作用被 TAM 阻断，这表明 T 对 GH 信号通路的作用似乎是由雌激素介​​导的。