Activin A specifically suppresses the expression of annexin A5 mRNA and augments gonadotropin-releasing hormone stimulation of A1 expression in LβT2 gonadotrope cells
Activin A specifically suppresses the expression of annexin A5 mRNA and augments gonadotropin-releasing hormone stimulation of A1 expression in LβT2 gonadotrope cells
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DOI：
10.1507/endocrj.ej22-0095
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发表时间：
2022-05-19
影响因子：
2
通讯作者：
Kawaminami, Mitsumori
中科院分区：
文献类型：
--
作者：
Murata, Takuya;Chiba, Shuichi;Kawaminami, Mitsumori
最近，我们报道了促性腺激素释放激素（GnRH）通过L β T2细胞中的GnRH受体-有丝分裂原活化蛋白激酶级联反应刺激膜联蛋白A1（Anxa 1）和A5（Anxa 5）mRNA表达。由于L β T2细胞对激活素有反应，我们检测了激活素A对L β T2细胞中Anxa 1和a5表达的影响。激活素A（0.4和4 ng/mL）处理以剂量依赖性方式降低Anxa 5 mRNA水平，但在浓度高达40 ng/mL时不影响Anxa 1 mRNA水平。在激活素A处理（4 ng/mL）后，Anxa 5 mRNA水平在6 h显著降低，逐渐下降直至24 h，并保持低水平直至48 h，而Anxa 1 mRNA水平在处理后无显著变化。激活素A预处理24 h使GnRH激动剂（GnRHa）诱导的Anxa 1增加约7倍，但Anxa 5不受影响。如前所述，这些激活素A处理增加了促性腺激素β亚基和GnRH受体mRNA水平，并略微降低了常见α-糖蛋白亚基mRNA水平。此外，我们检查了激活素A对Nr 4a 3的影响，Nr 4a 3被ANXA 5抑制并降低Fshb表达，发现激活素A增强了Nr 4a 3的表达并轻微降低了GnRHa诱导的Nr 4a 3的增加。这些结果表明，在促性腺细胞中，调节Anxa 1和a5表达的机制与激活素A信号转导差异偶联。激活素A在Nr 4a 3表达增加的情况下抑制Anxa 5表达，而激活素A和GnRH协同刺激Anxa 1表达。这些促性腺激素释放激素诱导的膜联蛋白在促性腺激素细胞中可能具有不同的特异性功能。
Recently, we reported that gonadotropin-releasing hormone (GnRH) stimulates annexin A1 (Anxa1) and A5 (Anxa5) mRNA expression through the GnRH-receptor-mitogen-activated protein kinase cascade in L beta T2 cells. As L beta T2 cells respond to activin, we examined the effect of activin A on Anxa1 and a5 expression in L beta T2 cells. Activin A (0.4 and 4 ng/mL) treatment decreased Anxa5 mRNA levels in a dose-dependent manner, but did not affect Anxa1 mRNA levels at concentrations up to 40 ng/mL. After activin A treatment (4 ng/mL), Anxa5 mRNA levels significantly decreased at 6 h, gradually declined until 24 h, and remained low until 48 h, whereas Anxa1 mRNA levels did not significantly change following treatment. Pretreatment with activin A for 24 h increased GnRH agonist (GnRHa)-induced Anxa1 increase by approximately 7-fold compared with GnRHa stimulation alone, but Anxa5 was not affected. As previously reported, these activin A treatments increased gonadotropin beta subunit and GnRH receptor mRNA levels and slightly decreased common alpha-glycoprotein subunit mRNA levels. Furthermore, we examined the effect of activin A on Nr4a3, which is repressed by ANXA5 and which reduces Fshb expression, and found that activin A augmented Nr4a3 expression and slightly decreased the GnRHa-induced increase in Nr4a3. These results suggest that in gonadotrope cells, the mechanism regulating Anxa1 and a5 expression is differentially coupled with activin A signal transduction. Activin A suppresses Anxa5 expression under increased Nr4a3 expression, whereas activin A and GnRH synergistically stimulate Anxa1 expression. These GnRH-inducible annexins may have different specific functions in gonadotropes.