Download PDF
Horm Metab Res 2001; 33(12): 733-738
DOI: 10.1055/s-2001-19134
Original Clinical
© Georg Thieme Verlag Stuttgart · New York

Rapid Effects of Calciotropic Hormones on Female Rat Enterocytes: Combined Actions of 1,25(OH)2-Vitamin D3, PTH and 17β-Estradiol on Intracellular Ca2+ Regulation

G. Picotto
  • Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, Bahia Blanca, Argentina
Further Information

Publication History

Publication Date:
18 December 2001 (online)

Also available at
    Permissions and Reprints

1,25(OH)2-Vitamin D3 [1,25(OH)2D3], PTH and 17β-estradiol increase intracellular Ca2+ levels ([Ca2+]i) in rat enterocytes by stimulating inner Ca2+ store mobilization and voltage-dependent Ca2+ channels through non-genomic activation of second-messenger cascades. The participation of store-operated Ca2+ (SOC) channels in 17β-estradiol regulation of enterocyte [Ca2+]i has also been suggested. The aim of this work was to investigate whether PTH and/or 17β-estradiol exert additive or synergistic effects acting in concert with the classic intestinal calciotropic hormone 1,25(OH)2D3. Fura-2-loaded rat duodenal cells were stimulated using rPTH [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] [31] [32] [33] [34] (10 nM), 17β-estradiol (0.1 nM) or 1,25(OH)2D3 (0.1 nM). The resulting Ca2+ signal was characterized by an almost immediate rise in [Ca2+]i (within 30 s) rapidly reaching peak levels, followed by a plateau phase that remained sustained as long as the cells were exposed to the stimulus. The addition of PTH at the sustained phase induced by 1,25(OH)2D3 or, conversely, the addition of the secosteroid after the PTH-induced effect, did not induce additional increases in [Ca2+]i. Simultaneous treatment with both hormones resulted in an elevation of [Ca2+]i equivalent to the maximal level caused by either agonist alone, suggesting common components for [Ca2+]i stimulation by PTH and 1,25(OH)2D3. Treatment with 17β-estradiol at the sustained phase induced by 1,25(OH)2D3 or, conversely, treatment with the secosteroid after the 17β-estradiol effect, induced additional increments in [Ca2+]i (58 % and 63 %, respectively). Simultaneous treatment of enterocytes with both steroids potentiated their individual effects to the same extent as when added sequentially, also indicative of additive actions mediated by different sources of calcium signaling cascades. Moreover, 17β-estradiol failed to further increase the 1,25(OH)2D3-induced initial Ca2+ elevation in Ca2+-free medium, thus suggesting that extracellular influx mechanisms rather than intracellular Ca2+ mobilization account for estrogen potentiation of 1,25(OH)2D3 modulation of [Ca2+]i in duodenal cells.

Key words:

Enterocytes - Intestine - Intracellular Calcium - 1,25(OH)2D3 - - 17β-Estradiol - PTH - Non-Genomic Effects - Combined Actions

References

  • 1 Nordin B EC. Calcium in human biology.  Berlin Heidelberg: ; Springer-Verlag, 1988
    Google Scholar
  • 2 Kleeman K, Kleeman C R. Parathyroid hormone and calcitonin.  In: Ingbar SH (ed.) Contemporary Endocrinology.  New York:; Plenum Publishing Corp, 1979: 305-322
    Google Scholar
  • 3 Nemere I, Szego C M. Early actions of parathyroid hormone and 1,25-dihydroxy-cholecalciferol on isolated ephitelial cells from rat intestine: I. Limited lysosomal enzyme release and calcium uptake.  Endocrinology. 1981;  108 1450-1462
    PubMedGoogle Scholar
  • 4 Picotto G, Massheimer V, Boland R. Parathyroid hormone stimulates calcium influx and the cAMP messenger system in rat enterocytes.  Am J Physiol. 1997;  273 C1349-C1353
    PubMedGoogle Scholar
  • 5 Massheimer V, Picotto G, Boland R, Boland A R, de. Effect of aging on the mechanisms of PTH-induced calcium influx in rat intestinal cells.  J Cell Physiol. 2000;  182 429-437
    CrossrefPubMedGoogle Scholar
  • 6 Chase L R, Aurbach G D. The effect of parathyroid hormone on the concentration of adenosine 3',5'-monophosphate in skeletal tissue in vivo.  J Biol Chem. 1970;  245 1520-1526
    CrossrefPubMedGoogle Scholar
  • 7 Hruska K. , Moskowitz D, Esbrit P, Civitelli R, Westbrook S, Huskey M. Stimulation of inositol phosphate and diacylglycerol production in renal tubular cells by parathyroid hormone.  J Clin Invest. 1988;  81 1804-1809
    PubMedGoogle Scholar
  • 8 Carson-Jurica M A, Schrader W T, O'Malley B W. Steroid receptor family: structure and functions.  Endocr Rev. 1990;  11 201-220
    PubMedGoogle Scholar
  • 9 Lieberherr M J. Effects of vitamin D3 metabolites on cytosolic free calcium in confluent mouse osteoblasts.  J Biol Chem. 1987;  262 13 168-13 173
    PubMedGoogle Scholar
  • 10 De Boland A R, Nemere I J. Rapid actions of vitamin D compounds.  J Cell Biochem. 1992;  49 32-36
    CrossrefPubMedGoogle Scholar
  • 11 De Boland A R, Boland R. Non-genomic signal transduction pathway of vitamin D in muscle.  Cell Signal. 1994;  6 717-724
    CrossrefPubMedGoogle Scholar
  • 12 Wehling M. Specific, nongenomic actions of steroid hormones.  Annu Rev Physiol. 1997;  59 365-393
    CrossrefPubMedGoogle Scholar
  • 13 Massheimer V, Boland R, De Boland A R. Rapid 1,25(OH)2-vitamin D3 stimulation of calcium uptake by rat intestinal cells involves a dihydropyridine-sensitive cAMP-dependent pathway.  Cell Signal. 1994;  6 299-304
    CrossrefPubMedGoogle Scholar
  • 14 Massheimer V, Picotto G, De Boland A R, Boland R. Ageing alters the rapid stimulation of cAMP-dependent calcium uptake by 1,25-dihydroxyvitamin D3 in rat intestinal cells.  Endocrinol and Metab. 1995;  2 157-163
    PubMedGoogle Scholar
  • 15 De Boland A R, Facchinetti M M, Balogh G, Massheimer V, Boland R. Age-associated decrease in inositol 1,4,5-trisphosphate and diacylglycerol generation by 1,25(OH)2-vitamin D3 in rat intestine.  Cell Signal. 1996;  8 l53-l57
    PubMedGoogle Scholar
  • 16 Balogh G, De Boland A R, Boland R. Influence of age on 1,25(OH)2-vitamin D3 activation of protein kinase C in rat duodenum.  Mol Cell Endocrinol. 1997;  129 127-133
    CrossrefPubMedGoogle Scholar
  • 17 Lucas P, Roulet C, Duchambon P, Lacour B, Drueke T. Rapid stimulation of calcium uptake by isolated rat enterocytes by 1,25(OH)2D3.  Pflugers Archiv. 1989;  413 407-413
    CrossrefPubMedGoogle Scholar
  • 18 de Boland A R, Norman A W. Influx of extracellular calcium mediates 1,25(OH)2D3-dependent transcaltachia, the stimulation of duodenal Ca2+ transport.  Endocrinology. 1990;  127 2475-2480
    PubMedGoogle Scholar
  • 19 De Boland A R, Norman A. Evidence for involvement of protein kinase C and cyclic adenosine 3',5' monophosphate-dependent protein kinase in 1,25-dihydroxy-vitamin D3-mediated rapid stimulation of intestinal calcium transport (transcaltachia).  Endocrinology. 1990;  127 39-45
    PubMedGoogle Scholar
  • 20 Picotto G, Massheimer V, Boland R. Acute stimulation of intestinal cell calcium influx induced by 17β-estradiol via the cAMP messenger system.  Mol Cell Endocrinol. 1996;  119 129-134
    CrossrefPubMedGoogle Scholar
  • 21 Picotto G, Vazquez G, Boland R. 17β-oestradiol increases intracellular Ca2+ concentration in rat enterocytes: potential role of phospholipase C-dependent store-operated Ca2+ influx.  Biochem J. 1999;  339 71-77
    CrossrefPubMedGoogle Scholar
  • 22 Wali R K, Baum C L, Sitrin M D, Brasitus T A. 1,25(OH)2D3 stimulates membrane phosphoinositides turnover, activates protein kinase C and increases cytosolic calcium in rat colonic epithelium.  J Clin Invest. 1990;  85 1296-1303
    PubMedGoogle Scholar
  • 23 Doolan C M, Condliffe S B, Harvey B J. Rapid non-genomic activation of cytosolic cyclic AMP-dependent protein kinase activity and [Ca2+]i by 17β -oestradiol in female rat distal colon.  British J Pharmacol. 2000;  129 1375-1386
    PubMedGoogle Scholar
  • 24 Lieberherr M, Grosse B, Duchambon P, Drueke T. A functional cell surface type receptor is required for the early action of 1,25-dihydroxyvitamin D3 on the phosphoinositide metabolism in rat enterocytes.  J Biol Chem. 1989;  264 20 403-20 406
    PubMedGoogle Scholar
  • 25 Facchinetti M, De Boland A R. Aging and calcitriol regulation of IP3 production in rat skeletal muscle and intestine.  Horm Metab Res. 2001;  33 10-15
    Article in Thieme ConnectPubMedGoogle Scholar
  • 26 Schiller C, Gruber R, Redlich K, Ho G, Katzgraber F, Willheim M, Pietshmann P, Peterlik M. 17β-estradiol antagonizes effects of 1,α25-dihydroxyvitamin D3 on interleukine 6 production and osteoclast-like cell formation in mouse marrow primary cultures.  Endocrinology. 1997;  138 4567-4571
    CrossrefPubMedGoogle Scholar
  • 27 Li W, Duncan R L, Karin N J, Farach-Carson M C. 1,25(OH)2D3 enhances PTH-induced Ca2+ transients in preosteoblasts by activating L-type Ca2+ channels.  Am J Physiol. 1997;  273 E599-E605
    PubMedGoogle Scholar
  • 28 Liel Y, Shany S, Smirnoff P, Schwartz B. Estrogen increases 1,25-dihydroxyvitamin D receptors expression and bioresponse in rat duodenal mucosa.  Endocrinology. 1999;  140 280-285
    CrossrefPubMedGoogle Scholar
  • 29 Colin E M, Van der Bemd G J, Aken M V, Christakos S, DeJonge H R, DeLuca H F, Prahl J M, Birkenhager J C, Buurman C J, Pols H A, Van Leeuwen J P. Evidence for involvement or 17β-estradiol in intestinal calcium absorption independent of 1,25-dihydroxyvitamin D3 level in the rat.  J Bone Min Res. 1999;  14 57-63
    PubMedGoogle Scholar
  • 30 Walters J, Weiser M. Calcium transport by rat duodenal villus and crypt basolateral membranes.  Am J Physiol. 1987;  252 G170-G177
    PubMedGoogle Scholar
  • 31 Weiser M. Intestinal epithelial cell surface membrane glycoprotein synthesis: I. An indicator of cellular differentiation.  J Biol Chem. 1973;  218 2536-2541
    PubMedGoogle Scholar
  • 32 Grynkiewicz G, Poenie M, Tsien R Y. A new generation of Ca2+ indicators with greatly improved fluorescent properties.  J Biol Chem. 1985;  260 3440-3450
    PubMedGoogle Scholar
  • 33 Snedecor G W, Cochran W G. Statistical Methods.  Ames, Iowa:; The Iowa State University Press, 1967: 120-134
    Google Scholar
  • 34 Vazquez G, De Boland A R, Boland R. 1,25-dihydroxy-vitamin D3-induced store-operated Ca2+ influx in skeletal muscle cells: Modulation by phospholipase C, PKC and tyrosine kinases.  J Biol Chem. 1998;  273 33 954-33 960
    PubMedGoogle Scholar
  • 35 Sitrin M D, Bissonnette M, Bolt M J, Wali R, Khare S, Scaglione-Sewell B, Brasitus T A. Rapid effects of 1,25(OH)2-vitamin D3 on signal transduction systems in colonic cells.  Steroids. 1999;  64 137-142
    CrossrefPubMedGoogle Scholar
  • 36 Picotto G. Non-genomic regulation of intestinal calcium transport in mammals by estrogens and calciotropic hormones.  Universidad Nacional del Sur, Argentina:; Ph. D. Thesis, Library code number R040/374.192, B148, 1999
    Google Scholar
  • 37 Jackson T R, Patterson S I, Thastrup O, Hanley M R. A novel tumor promoter, thapsigargin, transiently increases cytoplasmic free Ca2+ without generation of inositol phosphates in NG 115 - 401L neuronal cells.  Biochem J. 1988;  253 81-86
    PubMedGoogle Scholar
  • 38 Birnbaumer L, Zhu X, Meisheng J, Boulay F, Peyton M, Vannier B, Brown D, Platano D, Sadeghi H, Stefani E, Birnbaumer M. On the molecular basis and regulation of cellular capacitative calcium entry: Roles for Trp proteins.  Proc Natl Acad Sci USA. 1996;  93 15 195-15 202
    PubMedGoogle Scholar
  • 39 Suh B C, Song S K, Kim Y K, Kim K T. Induction of cytosolic Ca2+ elevation mediated by Mas-7 through pore formation.  J Biol Chem. 1996;  271 32 753-32 759
    PubMedGoogle Scholar
  • 40 Homoidan F R, Donowitz M, Weiland G A, Sharp G W. Two calcium channels in basolateral membranes of rabbit ileal epithelial cells.  Am J Physiol. 1989;  257 G86-G-93
    PubMedGoogle Scholar

Dr. Gabriela Picotto

Dept. Biología, Bioquímica y Farmacia
Universidad Nacional del Sur

San Juan 670
8000 Bahia Blanca
Argentina


Phone: + 54 (291) 459 51 00, ext. 2430

Fax: + 54 (291) 459 51 30

Email: gpicotto@criba.edu.ar

      >