title: Parathyroid hormone secretion by multiple distinct cell populations, a time dynamic mathematical model.
abstract: The acute response of parathyroid hormone to perturbations in serum ionized calcium ([Ca(2+)]) is physiologically complex, and poorly understood. The literature provides numerous observations of quantitative and qualitative descriptions of parathyroid hormone (PTH) dynamics. We present a physiologically based mathematical model of PTH secretion constructed from mechanisms suggested in the literature, and validated against complex [Ca(2+)] clamping protocols from human data. The model is based on two assumptions. The first is that secretion is a fraction of cellular reserves, with the fraction being determined by the kinetics of [Ca(2+)] with its receptor. The second is that there are multiple distinct populations of parathyroid cells, with different secretory parameters. The steady state and transient PTH secretion responses of the model are in agreement with human experimental PTH responses to different hypocalcemia and hypercalcemia stimuli. This mathematical model suggests that a population of secreting cells is responsible for the PTH secretory dynamics observed experimentally.
authors.affiliation: Department of Physiology, Center for Computational Medicine, University of Mississippi Medical Center, Jackson, 39216, Mississippi.
authors.forename: William A
authors.initials: WA
authors.lastname: Pruett
authors.affiliation: Department of Physiology, Center for Computational Medicine, University of Mississippi Medical Center, Jackson, 39216, Mississippi.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Hester
keywords: Calcium; hysteresis; parathyroid hormone; simulation
references.citation: Metabolism. 1978 Aug;27(8):993-1001
references.pmid: 672619
references.citation: Nephrol Dial Transplant. 1999 Oct;14(10):2398-406
references.pmid: 10528664
references.citation: Nephrol Dial Transplant. 2001 Jun;16(6):1214-21
references.pmid: 11390723
references.citation: J Cell Biol. 1979 Dec;83(3):521-8
references.pmid: 230190
references.citation: Scand J Clin Lab Invest. 1997 Aug;57(5):381-94
references.pmid: 9279963
references.citation: Eur J Endocrinol. 2003 Apr;148(4):403-11
references.pmid: 12656660
references.citation: Bone. 2010 Jan;46(1):49-63
references.pmid: 19732857
references.citation: Nephrol Dial Transplant. 1999 Apr;14(4):811-3
references.pmid: 10328447
references.citation: J Clin Invest. 1993 Feb;91(2):595-601
references.pmid: 8381822
references.citation: Math Biosci. 2010 Jul;226(1):46-57
references.pmid: 20406649
references.citation: Microsc Res Tech. 1995 Oct 1;32(2):148-63
references.pmid: 8580509
references.citation: Eur J Endocrinol. 2002 Mar;146(3):411-8
references.pmid: 11888849
references.citation: J Clin Endocrinol Metab. 1996 Dec;81(12):4236-43
references.pmid: 8954021
references.citation: J Clin Invest. 1986 Nov;78(5):1296-301
references.pmid: 3771798
references.citation: J Clin Invest. 2007 Dec;117(12):4003-8
references.pmid: 17992255
references.citation: Trans Assoc Am Physicians. 1986;99:189-96
references.pmid: 3603922
references.citation: Eur J Endocrinol. 1994 Apr;130(4):394-401
references.pmid: 8162171
references.citation: J Bone Miner Res. 1996 Jul;11(7):970-6
references.pmid: 8797118
references.citation: J Mol Endocrinol. 2008 Jan;40(1):13-21
references.pmid: 18096993
references.citation: J Clin Invest. 1981 Mar;67(3):885-92
references.pmid: 7204561
references.citation: Am J Physiol. 1992 Aug;263(2 Pt 1):E195-8
references.pmid: 1514598
references.citation: Am J Physiol. 1973 May;224(5):1143-8
references.pmid: 4349532
references.citation: J Clin Endocrinol Metab. 1983 Mar;56(3):572-81
references.pmid: 6822654
references.citation: Clin Endocrinol (Oxf). 1998 Jun;48(6):725-32
references.pmid: 9713561
references.citation: Scand J Clin Lab Invest. 1993 Oct;53(6):601-5
references.pmid: 8266006
references.citation: J Clin Endocrinol Metab. 2000 Dec;85(12):4789-94
references.pmid: 11134144
references.citation: Endocrinology. 1991 Jan;128(1):488-95
references.pmid: 1986940
references.citation: J Clin Endocrinol Metab. 1990 Aug;71(2):370-8
references.pmid: 2380334
references.citation: Kidney Int. 1994 Dec;46(6):1713-20
references.pmid: 7700031
references.citation: J Clin Invest. 1983 Dec;72(6):1924-9
references.pmid: 6643680
references.citation: Endocrinology. 1975 Aug;97(2):431-41
references.pmid: 1157761
references.citation: J Bone Miner Res. 1994 Jul;9(7):971-6
references.pmid: 7942165
references.citation: Kidney Int. 1993 May;43(5):1104-9
references.pmid: 8510389
references.citation: Curr Opin Nephrol Hypertens. 2008 Jul;17(4):363-7
references.pmid: 18660671
references.citation: Endocrinology. 1999 May;140(5):2224-31
references.pmid: 10218975
references.citation: Endocrinology. 1992 Dec;131(6):2638-42
references.pmid: 1446605
references.citation: Kidney Int Suppl. 1999 Dec;73:S2-7
references.pmid: 10633456
references.citation: Endocrinology. 1990 Mar;126(3):1720-7
references.pmid: 2407521