TRH and somatostatin (SRIH) are well known to stimulate and to inhibit TSH secretion respectively. However, the mechanisms underlying the effect of SRIH on thyrotrophs are still not understood. We have previously shown in vitro that the TSH response to TRH is potentiated in Ca2+-dependent fashion through the activation of dihydropyridine (DHP)-sensitive Ca2+ channels by the prepro-TRH (160-169) cryptic peptide (PS4) and tri-iodo-L-thyronine (T-3), when the hormone was added shortly before a TRH pulse in order to avoid its genomic effect. Using perifused rat pituitary fragments, the present study has shown that SRIH inhibits, in a dose-dependent manner, the TSH response to physiological concentration of TRH (10 nM) and reverses the Ca2+-dependent potentiation of that response induced either by PS4 or by T-3. We have also demonstrated that the inhibition by SRIH of the T-3 potentiation of TRH-induced TSH secretion is pertussis toxin-sensitive. Our data suggest that SRIH inhibits the PS4 and T-3 potentiation of TRH-induced TSH secretion through the inactivation of DHP-sensitive Ca2+ channels. Using primary cultures of rat anterior pituitary cells and videomicroscopy, we have already demonstrated that TRH, as well as PS4 and T-3, are able to increase intracellular Ca2+ concentration ([Ca2+](i)) rapidly, in 15 s. Our study has shown that SRIH is able to abolish the acute rise in [Ca2+](i) induced either by PS4 or by T-3 Since [Ca2+](i) responses to PS4 and T-3 are also abolished by the DHP nifedipine, our results suggest that [Ca2+](i) changes in PS4- or T-3-sensitive pituitary cells depend directly or indirectly on the activation of DHP-sensitive Ca2+ channels and that the inhibitory effect of SRIH may be mediated by inactivation of this type of channel.
