Differentiation-dependent expression of calcitriol actions on absorptive processes in cultured chick intestine: modulation by triiodothyronine

Abstract

Embryonic chick jejunum maintained in organ-culture exhibits a characteristic stage-specific pattern of responses to calcitriol and T3. Whereas induction of luminal Na+/inorganic phosphate and Na+/D-glucose transport by calcitriol was only possible at an advanced state of differentiation prior to hatching on day 20, the sterol induced cellular calcium transport with high efficiency even in undifferentiated enterocytes in day 15 embryonic intestine. T3 had no effect at all on calcium transport, but induced Na+/inorganic phosphate transport at all stages of epithelial maturation. In contrast, Na+/D\x=req-\ glucose transport was effectively induced by T3 only in relatively immature intestinal epithelium. T3, at a medium concentration of 10\m=-\8mol/l, in a permissive fashion potentiated the effects of calcitriol (10\ m=-\ 10\ m=-\ 10\ m=-\ 7mol/l) on calcium transport as well as on Na+/inorganic phosphate and Na+/D-glucose transfer. Thereby, T3 facilitated induction of transport activities by calcitriol against differentiation-related restraints. By facilitating the expression of genomic actions of calcitriol, T3 may thus play an important role in the regulation of calcium and phosphate metabolism.It has long been known that dysfunctions of the thyroid gland are frequently associated with dis¬ turbances of calcium and inorganic phosphate (P¡) homeostasis. It is, therefore, obvious that thyroid hormones must play an important role in mineral metabolism (reviewed in 1), although the actions at the cellular level constituting their function as cal¬ cium and P¡ regulating hormones are not clarified at all. Within the wide spectrum of thyroid hor¬ mone effects, a number of actions on bone, the kidney and small intestine resemble those of the classic calciotropic hormone, calcitriol (1,25-dihydroxyvitamin D3): Thus, thyroid hormones can stimulate bone résorption (2), enhance renal tubu¬ lar reabsorption of P¡ (3), and increase Na+ gradi¬ ent-driven uptake of P¡ by the small intestine (4). We want to emphasize that thyroid hormones may play an additional role in mineral metabolism owing to their ability to potentiate the genomic ef¬ fects of calcitriol on calcium and P¡ absorption by the small intestine: Utilizing an organ culture system of embryonic chick jejunum (5), we were able to show that the various genomic effects of calcitriol on intestinal transport of calcium (6-8) and P¡ (9) are markedly enhanced by triiodothyronine (10,11). In addition, calcitriol-related absorp¬ tion of D-glucose (12) can also be augmented by T3 in a synergistic fashion (11). We reported previ¬ ously that the expression of vitamin D3 action on these absorptive functions of enterocytes depends on the state of embryonic development and thus on the degree of epithelial cell differentiation (13). We therefore sought to explore the possibility that the stage-specific expression of calcitriol actions on in¬ testinal calcium uptake as well as on Na+/P¡ and Na+/D-glucose transport could be modulated by T,. Materials and MethodsFertilized eggs were ob...

1,25‐Dihydroxycholecalciferol‐related Na+/D‐glucose transport in brush‐border membrane vesicles from embryonic chick jejunum

“…Triiodothyronine, which at day 20 of development apparently has no effect by itself on Na+/D-glucose transport in cultured embryonic jejunum (see also Prager et al, 1990;Cross and Peterlik, 1991), amplifies the effect of calcitriol on Na'/ D-glucose transport across the brush-border membrane (Fig. 1).…”

“…Consequently, the possibility must be dismissed that in embryonic jejunum calcitriol could alter Na+-dependent D-glucose transport through an appropriate effect on the electrochemical Na' gradient. It seems that further differentiation of the enterocyte after hatching is required to allow the expression of the action of the sterol on Na+ transport across the brushborder membrane; this is not unlikely since other calcitriolmediated effects, particularly induction of Na+-dependent inorganic-phosphate transport, also exhibit stage-specific expression during development (Cross and Peterlik, 1982;Cross and Peterlik, 1991).…”

“…This was also reflected by an corresponding increase in the maximal velocity of the transfer process. Increased [3H]phlorizin binding after calcitriol treatment suggests that the steroid hormone activates Na+/D-glucose transport through increasing the number of carrier molecules in the brush-border membrane.10 nM triiodothyronine, which by itself has no effect on Na+-dependent D-glucose transport, potentiated the effect of 1,25-dihydroxycholecalciferol such that in the presence of both hormones, Na'/D-glucose-carrier activity was increased fourfold above control levels.Triiodothyronine has been shown to facilitate the expression of genomic effects of 1,25-dihydroxycholecalciferol (calcitriol) on calcium, Na f -dependent inorganic phosphate and D-glucose transport in organ-cultured embryonic chick jejunum (Cross et al, 1986;Cross and Peterlik, 1988;Cross and Peterlik, 1991). We had also demonstrated previously that calcitriol can increase Na+-dependent uptake of D-glucose from the intestinal lumen in two ways: by increasing the maximal velocity of the Na+/D-glucose transport system (Peterlik et al, 1981); through appropriate actions on pathways of Na + transfer across the brush-border membrane of enterocytes (Fuchs et al, 1985).…”

“…Triiodothyronine has been shown to facilitate the expression of genomic effects of 1,25-dihydroxycholecalciferol (calcitriol) on calcium, Na f -dependent inorganic phosphate and D-glucose transport in organ-cultured embryonic chick jejunum (Cross et al, 1986;Cross and Peterlik, 1988;Cross and Peterlik, 1991). We had also demonstrated previously that calcitriol can increase Na+-dependent uptake of D-glucose from the intestinal lumen in two ways: by increasing the maximal velocity of the Na+/D-glucose transport system (Peterlik et al, 1981); through appropriate actions on pathways of Na + transfer across the brush-border membrane of enterocytes (Fuchs et al, 1985).…”

Efeito da associação hipotireoidismo-castração no osso e nas paratireóides de ratas adultas

“…Sabe-se que nas deficiências de T3 e T4, a absorção intestinal de cálcio diminui (28), já que os hormônios tireoideanos aumentam o transporte intestinal do cálcio mediado pela vitamina D (29,30). Além disso, o hipotireoidismo altera o metabolismo do hormônio do crescimento (GH), reduzindo sua concentração plasmática (31)(32)(33).…”