Abstract
Histidyl-proline diketopiperazine [cyclo (His-Pro)] has recently been shown to inhibit prolactin (PRL) secretion in vitro and in vivo. This peptide is well known as a metabolite of thyrotropin-releasing hormone (TRH), which is one of the endogenous secretagogues of PRL. In this study, we investigated the effect of cyclo (His-Pro) on the cytosolic Ca2+ concentration ([Ca2+] i) in cultured lactotrophs by using a lactotroph-enriched fraction separated from female rat pituicytes by centrifugal elutriation. TRH (10nM) induced a rapid rise in [Ca2+] i in the lactotrophs, followed by a plateau phase of prolonged increase in [Ca2+] i. In contrast, the addition of 100μM of cyclo (His-Pro) caused no changes in the basal level or the TRH-induced plateau response of [Ca2+] i. Although pretreatment with cyclo (His-Pro) tended to decrease the biphasic increase in [Ca2+] i induced by TRH, the inhibitory effect was not statistically significant. These results demonstrated that cyclo (His-Pro) has no effect on [Ca2+] i in lactotrophs, and does not affect the TRH-induced increase in [Ca2+] i, indicating that the inhibition of PRL secretion by cyclo (His-Pro) may be primarily mediated by other intracellular messengers such as cyclic nucleotides and secondarily involved in other inhibitory systems including that of dopamine.
