Inhibitory effects of okadaic acid on thyrotropin and prolactin secretion from rat anterior pituitaries

The present study was undertaken to elucidate the effects of okadaic acid, a potent inhibitor of protein phosphatases, on thyrotropin (TSH) and prolactin (PRL) secretion, and on the hydrolysis of inositol phospholipids in rat anterior pituitaries. Preincubation of anterior pituitaries with okadaic acid caused a dose dependent decrease in TRH- and K(+)-induced TSH secretion, whereas basal secretion of TSH was not affected by pretreatment with okadaic acid. In contrast, okadaic acid resulted in a marked inhibition in both basal, and TRH- and K(+)-stimulated PRL release from anterior pituitaries. In addition, pretreatment with okadaic acid caused a slight, but significant decrease in the formation of [3H]inositol phosphate ([3H]IP) in rat anterior pituitaries. The present study suggests that okadaic acid blocks the release of TSH and PRL by inhibiting Ca2+ influx and that inhibitory effects of okadaic acid on PRL release are, at least in part, due to the inhibition of inositol phospholipid hydrolysis.