Regulation of Prolactin Secretion from Pituitary Lactotrophs in the Presence of Activin

有报道称，激活素可以抑制泌乳素（PRL）和生长激素（GH）的合成和分泌，这两种激素的合成和分泌来源于垂体前细胞培养物或生长营养物质或乳营养物质的细胞系。最近也有报道称，激活素抑制了PRL的合成，但刺激了大鼠生长细胞来源的GH3细胞中GH的合成。所有这些实验中使用的培养基都含有血清。因此，推测在上述培养体系中，血清中的生长因子和细胞因子与激活素相互作用。抗生素也存在。氨基糖苷类是细胞培养中常用的抗生素，有报道称氨基糖苷类能抑制磷酸肌苷的水解。因此，除了血清中的生长因子和细胞因子外，抗生素也可能影响激活素的信号转导途径。为了研究激活素在不受其他因素干扰的情况下对PRL和GH合成的影响，我们在不添加血清和抗生素的情况下，用确定的培养基建立了GH3细胞的培养体系。我们发现激活素刺激了该系统中PRL和GH的合成。观察到时间依赖性和剂量依赖性刺激。激活素结合蛋白卵泡抑素以剂量依赖的方式抑制激活素存在下PRL和GH合成的增加。我们还发现MAP激酶抑制剂在激活素存在的情况下抑制了PRL和GH合成的增加。激活素可能通过与MAP激酶通路相互作用调节PRL和GH的合成。

It has been reported that activin suppressed the synthesis and secretion of prolactin (PRL) and growth hormone (GH) using the primary anterior pituitary cell culture or cell lines derived from somatotrophs or lactotrophs. Recently, it was also reported that activin suppressed the synthesis of PRL but stimulated the synthesis of GH in GH3 cells derived from rat somatolactotroph. The culture media used in all of these experiments contained sera. Therefore, it was speculated that the growth factors and cytokines in sera interacted with activin in the above culture systems. Antibiotics were also present. Aminoglidosids are the antibiotics often used in cell culture and it was reported that aminoglycosides suppressed the hydrolysis of phosphoinositide. Therefore, not only growth factors and cytokines in sera but also antibiotics might affect the signal transduction pathways of activin. In order to study the effect of activin on the synthesis of PRL and GH without other factors interfering, we established the culture system of GH3 cells using a defined medium without the addition of sera or antibiotics. We found that activin stimulated the synthesis of both PRL and GH in this system. Time dependent and dose dependent stimulation was observed. The activin binding protein follistatin suppressed the increased synthesis of PRL and GH in the presence of activin in a dose dependent manner. We also found that MAP kinase inhibitors inhibited the increased synthesis of PRL and GH in the presence of activin. Activin may regulate the synthesis of PRL and GH by interacting with MAP kinase pathways.