Decrease in CGRP and CT levels either contained in or released by CA-77 C cells after combined treatments with 1,25-dihydroxyvitamin D ₃ analogues and 9-cis retinoic acid

Abstract

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.

Associations between dairy foods, diabetes, and metabolic health: Potential mechanisms and future directions

“…In addition to conveying signals in an afferent manner away from peripheral tissues (pain, temperature, proprioception, noxious chemical signals), some peripheral neurons act in an efferent fashion to secrete CGRP, which can impinge upon inflammation and hemodynamics (see [60, 61]). CGRP expression by spinal cord neurons is up-regulated by dietary Ca in the rat [62] and expression is reduced by calcitriol treatment of C-cells or thyroid cells in culture [63–65]. This calcium- and inflammation-regulated peptide appears to have important immunomodulatory actions by 1) tempering inflammation through NFkB inhibition and 2) increasing endothelial production of PGI 2 , a prostaglandin with anti-inflammatory activities [61].…”

The relationship between thyroid disorders and vitamin A.: A narrative minireview

“…The effect of retinol on thyroid C cells is still unknown (4). An in vitro study on the rat C cell line CA-77 showed a decrease in calcitonin release due to retinoid acid 9-cis (55), while all-trans retinoic acid did not seem to have an effect on a human medullary thyroid carcinoma cell line (56). Furthermore, no data suggest the physiological presence of retinoids in thyroid parafollicular cells (3).…”

Vitamin A, endocrine tissues and hormones: interplay and interactions

“…No information has been reported about a role of RA and calcitonin secretion by normal thyroid C cells. In vitro , 9-cis RA decreases the release of calcitonin in the rat C cell line CA-77 ( 57 ), but no data are available about the spontaneous presence of 9-cis RA in C cells. atRA had no significant effect on a human medullary thyroid carcinoma cell line ( 58 ).…”