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 a Ca(2+)-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 (T3), 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 Ca(2+)-dependent potentiation of that response induced either by PS4 or by T3. We have also demonstrated that the inhibition by SRIH of the T3 potentiation of TRH-induced TSH secretion is pertussis toxin-sensitive. Our data suggest that SRIH inhibits the PS4 and T3 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 T3, 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 T3. Since [Ca2+]i responses to PS4 and T3 are also abolished by the DHP nifedipine, our results suggest that [Ca2+]i changes in PS4- or T3-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.

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The effects of 16 days of oral treatment with thyrotropin-releasing hormone (TRH, 1 mg/24 h) on serum levels of thyrotropin (TSH), thyroxine (T₄) and triiodothyronine (T3) and the kinetics of TRH in the blood were studied in normal rats. A second group of animals served as controls. TRH was dissolved by sonification (10 mg/l) and was stable in tap water. TRH was measured by a radioimmunoassay procedure (normal range: 20–80 pmol/l, antiserum K2B9 1:120,000 final dilution). An increase in basal TSH (7,200 ± 440 ng/l, mean ± SD) was found after 2 days of treatment (11,420 ± 810 ng/l), but a significant increase was observed after 5 days of treatment (12,530 ± 640 ng/l, p < 0.001). T₄ serum concentrations remained in the normal range during the entire period of study, whereas T₃ serum concentrations (0.76 ± 0.1 µg/l) were increased to 1.22 ± 0.2 µg/l on day 5 (p < 0.001). A subsequent decline of TSH, T₄ and T₃ up to the end of the study was observed. TRH_max concentrations were registered on day 5 (790 ± 24 pmol/l). The mean value of TRH_max was 723 ± 34 pmol/l. To improve the stability of TRH in tap water, 1-ml samples of drinking water with dissolved TRH were measured. The mean TRH concentration in drinking water was 73 ± 1.5% (SD). No significant correlations were found between the area under the curve of TSH (184,340 ng·l^–1·24 h) and that of TRH (14,954 pmol·l^–1·24 h). These findings suggest that (1) chronic treatment with oral TRH cannot induce hyperthyroidism in rats, (2) oral TRH is absorbed when dissolved in tap water where it is stable and (3) the enzymatic process of TRH degradation is saturated at high doses of the peptide used in this study. Chronic treatment with oral TRH is a useful model to study the pituitary reserves in relation to TRH blood levels.

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