We have characterized, by RT-PCR amplification using specific primers, the presence of glucagon-like peptide-I (GLP-I) receptor mRNA in CA-77 cells, a C cell line derived from a rat medullary thyroid carcinoma. Down-regulation of the GLP-1 receptor mRNA was observed after exposure of CA-77 C cells with GLP-1 (7-37). Increased secretion of both calcitonin gene-related peptide (CGRP) and calcitonin (CT) occurred after treatment with GLP-1 (7-37) associated with elevated steadystate levels of CGRP and CT mRNA. GLP-1 (7-37) increased cAMP formation in CA-77 cells in a dose-dependent manner; exendin (9-39), a GLP-1 receptor antagonist, inhibited cAMP production. The GLP-1 peptide which is produced by intestinal cells could be involved in the control of CT secretion through an entero-thyroidal axis implying GLP-1 receptor and increased CT gene expression.

Summary ― The effect of 17!-estradiol on calcitonin (CT) and calcitonin-gene-related peptide (CGRP) secretions in the murine CA-77 C cell line was studied after 1, 3, 5 and 6 d of treatment. The release of both CT and CGRP significantly increased 1, 3, 5 and 6 d after addition of 0.1 Ilmol/l estradiol alone to the culture medium. The C cell content of both peptides also increased after 6 d of treatment with the same dose of estrogen. The enhanced CT and CGRP secretions induced by 17(3-estradiol were not inhibited by the simultaneous addition of 5 wmol/I of all-trans-retinoic acid. Dexamethasone alone increased the release of both peptides within 6 d. However, when cells were treated simultaneously with estradiol and 1 pmol/I dexamethasone, the addition of retinoic acid blunted both the CT and CGRP secretions induced by dexamethasone. These results showed that the positive effects of 17(3-estradiol on both CT and CGRP secretions were modulated by dexamethasone and retinoic acid.CT secretion / CGRP secretion / CA-77 C cell / 17(3-estradiol / dexamethasone / retinoic acid Résumé ― Le 17p-oestradiol à la dose de 100 nmolll augmente la sécrétion et le contenu cellulaire de CT et de CGRP par la lignée de cellules C (CA-77) d'origine murine. Les effets de /'œsfrad/o/ sur la libération de CT et de CGRP dans le milieu de culture sont observés 1, 3, 5 et 6 j après addition du stéroïde. Le contenu cellulaire en hormones est également légèrement augmenté sous cestradiol. L'acide rétinoi'que all-trans 5 wmolll ne diminue la sécrétion des 2 peptides qu'au bout de 6 j, alors que la dexaméthasone 1 pmolll, seule, stimule la sécrétion de CT et CGRP tout au long du traitement (de 1 à 6 j). Si l'acide rétinoïque n affecte pas le contenu cellulaire en CT et CGRP, la dexaméthasone, en revanche, l'augmente. Le co-traitement par l'c!stradiol et l'acide rétinoique n'inhibe pas l'effet du sté-roïde sur la sécrétion de CT et de CGRP. Dans le cas d'un co-traitement par la dexaméthasone et l'oestradiol, un effet additif n'est observé qu'après 3 j de traitement. Le traitement simultané des cellules C par les 3 molécules montre à chaque fois (1, 3, 5 et

Summary ― This study examined the action of 9-cis retinoic acid and 1,25-dihydroxyvitamin D 3 analogues (KH 1060, EB 1089 and MC 903) on the release of calcitonin (CT) and calcitonin gene-related peptide (CGRP) in the rat C cell line CA-77. This cell line mainly secretes CGRP. Using radioimmunoassays (RIA S ) for CT and CGRP, we measured the release of both peptides in the culture medium as well as the amount of these proteins contained in the CA-77 C cells. 9-cis retinoic acid decreased the release of both CGRP and CT dose-dependently in the range between 1 nM and 1 pM. The half-effective dose was 10 nM. The treatment of CA-77 C cells with 0.1 1tM calcitriol alone only slightly decreased the release of both CT and CGRP. The increase in the amount of CT and CGRP released by the action of 1 1tM dexamethasone was reduced by 1 1tM 9-cis retinoic acid, and this effect was enhanced by the addition of 0.1 1tM calcitriol or KH 1060, EB 1089 and MC 903. When the C cells were continuously stimulated by dexamethasone, after 6 days of exposure to the combined treatment with calcitriol analogues + 9-cis retinoic acid, there was a greater decrease in the amount of CGRP contained in the C cells than after treatment with 9-cis retinoic alone. Our data suggested that combined treatment with retinoic acid and calcitriol analogues exerted a stronger inhibition on the amounts of the two peptides either contained in the cells or released in the medium than each hormone alone.