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

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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.