1,25-Dihydroxyvitamin D₃Has Opposite Effects on the Expression of Parathyroid Secretory Protein and Parathyroid Hormone Genes

Abstract

Previous studies have shown that 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] decreases levels of mRNA for prepro-PTH as well as PTH secretion after chronic exposure (24-48 h) of parathyroid cells in tissue culture. We have now extended these studies to determine the effects of the vitamin D3 metabolite on parathyroid secretory protein (PSP) gene expression. Primary cultures of bovine parathyroid cells were incubated with 10(-8) M 1,25-(OH)2D3 for periods of time ranging from 24-72 h. As observed in earlier experiments, prepro-PTH mRNA decreased to less than 50% of the control value after 72 h. In marked contrast, PSP mRNA showed a 2.5-fold increase by 24 h and greater than 7-fold stimulation by 72 h. In the same studies, PTH secretion was suppressed (to 60% of control), while PSP secretion was increased by 40% over control values. Exposure to high (2.5 mM) or low (0.5 mM) calcium had no effect on PSP mRNA, even though low calcium stimulated the secretion of PSP while high calcium suppressed secretion. These studies showed that 1,25-(OH)2D3 has opposite effects on the gene expression of PSP and PTH in bovine parathyroid cells in tissue culture.

Chromogranin A: current status as a precursor for bioactive peptides and a granulogenic/sorting factor in the regulated secretory pathway

“…CGA mRNA and protein abundance is suppressed by estrogen in the pituitary [33][34][35], and up-regulated by glucocorticoids in the pituitary and adrenal [25,[36][37][38]. CGA biosynthesis is enhanced by 1,25-dihydroxyvitamin D-3 in the parathyroid gland [39,40], although parathyroid hormone biosynthesis is inhibited by di-hydroxyvitamin D-3 [39]. Under these conditions, CGA is released at a higher rate, but total synthesis is not significantly affected [40].…”

“…The overall pattern of CGA biosynthesis regulation in the diffuse neuroendocrine system suggests that CGA is normally produced in excess in secretory cells and that episodes of increased secretion are accompanied by decreased degradation of CGA, rather than increased CGA gene transcription [39,43], although examples of up-regulation of CGA transcription in response to secretagogue stimulation may well be uncovered in future. The 'constitutive' regulation of CGA biosynthesis, compared to strong coupling of secretion and biosynthesis for other vesicle constituents [37] seems consistent with a role for CGA in granulogenesis (see below).…”

In VivoRegulation of Chromogranin A Messenger Ribonucleic Acid in the Parathyroid by 1,25-Dihydroxyvitamin D: Studies in Normal Rats and in Chronic Renal Insufficiency1

“…In vitro studies, using bovine parathyroid cells in primary culture, have shown that the transcription and secretion rates of PTH and CgA are regulated in opposite directions by 1,25-(OH) 2 D 3 (11)(12)(13)(14)(15). The sterol decreases PTH (8 -10) but increases CgA gene expression in a time-and concentrationdependent fashion (13,14). The regulation of PTH expression by Ca 2ϩ and 1,25-(OH) 2 D 3 has been confirmed in vivo (10,16,17).…”

Επίπεδα Των Μεταβολιτών Της Βιταμίνης D 25-Ohd 2425-(Oh)-2d 125 -(OH)-2D Και Οστεοκαλσίνης Σε Παιδιά Με Μεσογειακή Αναιμία

“…Ο πρώτος μηχανισμός είναι έμμεσος και συντελείται μέσω της αύξησης από την 1,25-(OH)2D του ιονισμένου Ca++ του ορού, που αποτελεί ένα παράγοντα αναστολής της σύνθεσης και έκκρισης της παραθορμόνης. Η 1,25-(OH)2D και η 24,25-(OH)2D αναστέλλουν και απευθείας τη σύνθεση της ορμόνης [112][113][114].…”

“…Η 1,25-(OH)2D βρέθηκε ότι προκαλεί καταστολή του m-RNA για την προ-προπαραθορμόνη και μεταβολές στη σύνθεση της. [113,114]. Ακόμη έχει προταθεί ένας μηχανισμός ρύθμισης της σύνθεσης της παραθορμόνης ανεξάρτητος από έκφραση γονιδίων [110].…”