Retinoids and vitamin D in skin and parathyroid glands

Abstract: Vitamin D3 (VitD3) and retinoids are important factors involved in differentiation and proliferation in many cell systems. Their effects in skin, where retinoids and vitamin D are known to be crucially involved in keratinocyte differentiation and function,, and in the parathyroid, the overall regulatory organ in calcium homeostasis were studied. It is discovered that transcripts for retinal-binding protein (RBP), cellular retinol binding protein (CRBP) I and cellular retinoic acid binding protein (CRABP) I and II are found in normal skin and keratinocytes. Decreased CRABP I and increased CRABP II mRNA expressions were found in lesional psoriatic skin compared with uninvolved skin. Transcripts for CRBP I, CRABP I and II, retinoic acid receptor (RAR) type α, β and γ and retinoic X receptor (RXR) α were also detected in human parathyroid adenomas. Cultured human and bovine parathyroid cells were able to produce all-trans retinoic acid (atRA) and 9-cis retinoic acid (9cRA) from all-trans-[11,12-3H]-retinol. VitD3, atRA and 9cRA were found to suppress parathyroid hormone (PTH) mRNA level and PTH secretion from human adenomatous and bovine parathyroid cells. Further, atRA, 9cRA and vitD3 inhibited proliferation of human parathyroid cells in vitro.Calcium receptors are crucially involved in sensing of extracellular calcium concentrations in the parathyroid. Two receptors are discovered; CAS (megalin, gp330; 550 kDa) and CaR (120 kDa); but their respective role in calcium homeostasis is not yet clarified. A recently established rat kidney proximal tubule cell line (IRPTC) express CAS, but not CaR, but nevertheless responds to changes in external calcium similar to parathyroid cells and placental cytotrophoblasts. CAS expression in IRPTC's increased after addition of atRA, 9cRA or VitD3, alone or in combinations, similar to what was seen in the human choriocarcinoma cell line JEG-3 and differentiated F9 cells (murine teratocarcinoma incubated with atRA and cAMP). In primary cultured bovine parathyroid cells, CaR, CAS and PTH mRNA levels gradually decreased during culture up to 5 days, and vitD3 atRA or 9cRA inhibited PTH mRNA but failed to influence CAS or CaR mRNA levels during this culture period.In conclusion, the results in this thesis confirm that parathyroid gland as well as skin are target organs of vitamins A and D, which are influencing cell proliferation, differentiation, and hormone production. These factors exert tissue specific effects on CAS mRNA expression.