Abstract
Phosphate administration increases both parathyroid hormone (PTH) secretion and parathyroid size in rats, but the relative contribution of hypertrophy and hyperplasia is unknown. Accordingly, we reexamined parathyroid histology in a previously published experiment [6], quantitatively rather than qualitatively. Ninety female Long-Evans rats were divided into six groups; three were given a normal deit, and three a high phosphate diet (Ca/P 1:7). One group from each arm was killed after 1, 2, and 3 months. Quantitative microscopy was performed on the parathyroid section with the largest area from each animal, without knowledge of its experimental status. Total gland area and total number of cell profiles did not change significantly in the control rats, but increased progressively in the phosphate-loaded rats. At 3 months, the difference was + 194% for gland area and + 151% for profile number (P<0.0001), much more than could be accounted for by suppression of apoptosis. Mean nuclear profile area and mean cell profile area (including associated connective tissue as well as cytoplasm) were both significantly increased at 1 month (P<0.0001). The differences persisted, but their magnitudes (about +16%) did not change further. This time course was consistent with the morphologic expression of increased PTH secretory activity. We conclude that phosphate administration to adult rats increases both size and number of parathyroid cells, the latter due to increased cell proliferation. Phosphate-stimulated parathyroid growth could be due to either hypocalcemia or decreased calcitriol production; increased cell division may also be linked to increased hormone secretion, regardless of its cause. The relative importance of these different mechanisms remains to be determined.
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Slatopolsky, E, Delmez JA (1994) Pathogenesis of secondary hyperparathyroidism. Am J Kidney Dis 23:229–236.
Reiss, E, Canterbury JM, Bercovitz MA, Kaplan EL (1970) The role of phosphate in the secretion of parathyroid hormone in man. J Clin Invest 49: 2146–2149
Borle AB, Clark I (1981) Effects of phosphate-induced hyperparathyroidism and parathyroidectomy on the rat kidney calcium in vivo. Am J Physiol 241 (Endocrinol Metab 4): E136-E141
Drake TG, Albright F, Castleman B (1937) Parathyroid hyperplasia in rabbits produced by parenteral phosphate administration. J Clin Invest 16: 203–206
Stoerk HC, Carnes WH (1945) The relation of the dietary Ca∶P ratio to serum Ca and to parathyroid volume. J Nutr 29: 43–50
Demeter JG, Jong SA, Oslapas R, Ernst K, Hessel P, Smith M, Nayyar R, Lawrence AM, Paloyan E (1991) High phosphate diet-induced primary hyperparathyroidism: an animal model. Surg 110: 1053–1060
Wernerson A, Widholm SM, Svensson O, Reinholt FP (1991) Parathyroid cell number and size in hypocalcemic young rats. APMIS 99: 1096–1102
Wernerson A, Svensson O, Reinholt FP (1989) Parathyroid cell number and size in hypocalcemic rats: a stereologic study employing modern unbiased estimators. J Bone Miner Res 4: 705–713
Brandi ML, Fitzpatrick LA, Coon HG, Aurbach GD (1986) Bone parathyroid cells: cultures maintained for more than 140 population doublings. Proc Natl Acad Sci 83: 1709–1713
Parfitt AM (1994) Parathyroid growth: normal and abnormal. In: Bilezikian JP, Levine MA, Marcus R (eds) The parathyroids—basic and clinical concepts. Raven Press, New York, pp 373–405
Gundersen HJG, Bendtsen TF, Korbo L, Marcussen N, Moller A, Nielsen K, Nyengaard JR, Pakkenberg B, Sorensen FB, Vesterby A, West MJ (1988) Some new, simple and efficient stereological methods and their use in pathological research and diagnosis. APMIS 96: 379–394
Gundersen HJG, Bagger P, Bendtsen TF, Evans SM, Korbo L, Marcussen N, Moller A, Nielsen K, Myengaard JR, Pakkenberg B, Sorensen FB, Vesterby A, West MJ (1988) The new stereological tools: disector, fractionator, nucleator and point sampled intercepts and their use in pathological research and diagnosis. APMIS 96: 857–881
Capen CC, Roth SI (1973) Ultrastructural and functional relationships of normal and pathologic parathyroid cells. In: Ioachim HL (ed) Pathobiology annual. Appleton-Century-Crofts, New York, pp 129–175
Lloyd HM, Jacobi JM, Cooke RA (1979) Nuclear diameter in parathyroid adenomas. J Clin Pathol 32:1278–1281
Lloyd HM, Parfitt AM, Jacobi JM, Willgoss DA, Craswell PW, Petrie JJB, Boyle PD (1989) The parathyroid glands in chronic renal failure: a study of their growth and other properties, based on findings in hypocalcemic patients. J Lab Clin Med 114:358–367
Kerr JFR, Searle J, Harmon BV, Bishop CJ (1987) Apoptosis. In: Potten CS (ed) Perspectives on mammalian cell death. Oxford University Press, Oxford, pp 93–128
Platt H (1950) Mitotic activity in the parathyroid glands of the rat following bilateral nephrectomy. J Pathol Bacteriol 62:383–387
Hughes MR Brumbaugh PF, Haussler MR, Werdegal JE, Baylink DJ (1975) Regulation of serum 1-alpha, 25-dihydroxyvitamin D3 by calcium and phosphate in the rat. Science 190:578–580
Portale AA, Halloran BP, Morris RC (1989) Physiologic regulation of the serum concentration of 1,25-dihydroxyvitamin D by phosphorus in normal men. J Clin Invest 83:1494–1499
Rodriguez M, Martin-Malo A, Martinez ME, Torres A, Felsenfeld AJ, Llach F (1991) Calcemic response to parathyroid hormone in renal failure: role of phosphorus and its effect on calcitriol. Kidney Int 40:1055–1062
Jacobi J, Lloyd HM, Meares JD (1977) Onset of oestrogen-induced prolactin secretion and DNA synthesis by the rat pituitary gland. J Endocrinol 72:35–39
Sakaguchi K (1994) Autocrine and paracrine functions of parathyroid tissue. In: Bilezikian JP, Levine MA, Marcus R (eds) The parathyroids—basic and clinical concepts. Raven Press, New York, pp 93–105
Hendy GN, Stotland MA, Grunbaum D, Fraher LJ, Loveridge N, Goltzman D (1989) Characteristics of secondary hyperparathyroidism in vitamin D-deficient dogs. Am J Physiol 256:E765-E772
Szabo A, Marke J, Beier E, Mall G, Ritz E (1989) 1,25(OH)2 vitamin D3 inhibits parathyroid cell proliferation in experimental uremia. Kidney Int 35:1049–1056
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Wang, Q., Paloyan, E. & Parfitt, A.M. Phosphate administration increases both size and number of parathyroid cells in adult rats. Calcif Tissue Int 58, 40–44 (1996). https://doi.org/10.1007/BF02509544
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DOI: https://doi.org/10.1007/BF02509544