Somatostatin blocks the potentiation of TRH-induced TSH secretion from perifused pituitary fragments and the change in intracellular calcium concentrations from dispersed pituitary cells elicited by prepro-TRH (PS4) or by tri-iodothyronine

Abstract

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.

Effects of Antihypertensive Drugs on Thyroid Function in Type 2 Diabetes Patients With Euthyroidism

“…The increased intracellular availability of Ca 2+ plays an important role in the regulation and secretion of thyroid hormones ( Lalau et al, 1987 ). Studies indicated that CCB could interfere with thyroid function through pituitary ( Brabant et al, 1989 ; Roussel et al, 1995 ; Roussel et al, 1997 ), thyroid ( Jangid, 1993 ; Pedemonte et al, 2005 ), and peripheral thyroid physiological process ( Capen, 1994 ). However, the clinical studies on the effect of CCB on thyroid function were inconsistent ( Isles et al, 1985 ; Haitas et al, 1986 ; Valensi et al, 1989 ).…”

“…However, the evidence for thyroid function-changing effect of second-and third-generation β 1 -adrenergic receptor blockers in euthyroid cases shows contrary outcomes (Kristensen and Weeke, 1977;Faber et al, 1979;Perret et al, 1984;Reeves et al, 1985;Kayser et al, 1991). The effect of ACEI, ARB (Hume et al, 1990;Vranckx et al, 1995;Andjelkovic et al, 2016) and CCB (Brabant et al, 1989;Jangid, 1993;Eidne et al, 1994;Roussel et al, 1995;Roussel et al, 1997;Pedemonte et al, 2005) on thyroid function were not consistent between animal study and clinical studies and the sample size was small (Isles et al, 1985;Haitas et al, 1986;Valensi et al, 1989;Andjelkovic et al, 2016).…”

Pituitary thyrotropic cells are affected by steroid hormones

“…The inhibitory action of somatostatin (SRIH) was confirmed by discrete lesions of SRIH neurons in the rat periventricular nucleus of the preoptic-anterior hypothalamus, leading to a transient elevation in GH and TSH secretion (84). Roussel et al (85) showed that SRIH inhibits TSH response to physiological concentrations of TRH in primary cultures of rat anterior pituitary cells in a dose-dependent manner. Similarly, increased hypothalamic SRIH levels induced by oral glucose administration, were found to suppress TRHstimulated TSH response in humans (86).…”

Is Ps4 (prepro-TRH [160-169]) More Than an Enhancer for Thyrotropin-Releasing Hormone?

“…In ing assays is obligatory due to the rapid cleavage of unmodified Ps4 by tissue extracts (7). Ps4 (13). The TSH response to TRH is potentiated in a Ca2+-dependent fashion through the activation of dihydropyridine (DHP)-sensitive Ca2+ channels by Ps4 and triiodothyronine (T3), when the hormone was added shortly before a TRH pulse in order to avoid its genomic effect.…”