Bone turnover markers in medicamentous and physiological hyperprolactinemia in female rats
Abstract
Background/Aim. There is a lack of data on the effects of prolactin on calcium metabolism and bone turnover in hyperprolactinemia of various origins. The aim of this study was to compare the influence of medicamentous and physiological hyperprolactinemia on bone turnover in female rats. Methods. Experimental animals (18 weeks old, Wistar female rats) were divided as follows: the group P – 9 rats, 3 weeks pregnant; the group M3–10 rats that were intramuscularly administrated sulpirid (10 mg/kg) twice daily for 3 weeks, the group M6 – 10 rats that were intramuscularly administrated with sulpirid (10 mg/kg) twice daily for 6 weeks, and age matched nulliparous rats as the control group: 10 rats, 18-week-old (C1) and 7 rats, 24 weeks old (C2). Laboratory investigations included serum ionized calcium and phosphorus, urinary calcium and phosphorous excretion, osteocalcin and serum procollagen type 1 N-terminal propeptide (P1NP). Results. Experimental animals in the group P compared to the control group, displayed lower mean serum ionized calcium (0.5 ± 0.2 vs 1.12 ± 0.04 mmol/L; p < 0.001); higher mean serum phosphorus (2.42 ± 0.46 vs 2.05 ± 0.2 mmol/L; p < 0.05); increased urinary calcium (3.90 ± 0.46 vs 3.05 ± 0.58; p < 0.01) and significantly increased P1NP (489,22 ± 46,77 vs 361.9 ± 53,01 pg/mL; p < 0.001). Experimental animals in the group M3 had significantly decreased P1NP, compared to the contol group. Prolongated medicamentous hyperprolactinemia (the group M6) induced increased serum ionized calcium (1.21 ± 0.03 vs 1.15 ± 0.02 mmol/L; p < 0.001); decreased serum phosphorus (1.70 ± 0.13 vs 1.89 ± 0.32 mmol/L; p < 0.001); decreased osteocalcin and P1NP. Conclusions. Physiological hyperprolactinemia does not have such harmful effect on bone metabolism as medicamentous hyperprolactinemia. Chronic medicamentous hyperprolactinemia produces lower serum levels of bone formation markers. Assessment of bone turnover markers in prolongated medicamentous hyperprolactinemia provides an opportunity for earlier diagnosis of bone metabolism disturbances and should be considered as mandatory.
References
Mancini T, Casanueva FF, Giustina A. Hyperprolactinemia and prolactinomas. Endocrinol Metab Clin North Am 2008; 37(1): 67−99.
Greenspan SL, Neer RM, Ridgway EC, Klibanski A. Osteoporosis in men with hyperprolactinemic hypogonadism. Ann Intern Med 1986; 104(6): 777−82.
Schlechte J, Khoury G, Kathol M, Walkner L. Forearm and verte-bral bone mineral in treated and untreated hyperprolactinemic amenorrhea. J Clin Endocrinol Metab 1987; 64(5): 1021−6.
Biller BM, Baum HB, Rosenthal DI, Saxe VC, Charpie PM, Kliban-ski A. Progressive trabecular osteopenia in women with hy-perprolactinemic amenorrhea. J Clin Endocrinol Metab 1992; 75(3): 692−7.
Vestergaard P, Jorgensen JOL, Hagen C, Hoeck HC, Laurberg P, Rejnmark L, et al. Fracture risk is increased in patients with GH deficiency or untreated prolactinomas - a case-control study. Clin Endocrinol (Oxf) 2002; 56(2): 159−67.
Zadrozna-Sliwka B, Bolanowski M, Kałuzny M, Syrycka J. Bone mineral density and bone turnover in hyperprolactinaemia of various origins. Endokrynol Pol 2007; 58(2): 116−22.
Adler RA, Farrell ME, Deiss WP, Krieg RJ, MacLeod RM. Hyper-calciuria in a new rat model of hyperprolactinemia. Metab Clin Exp 1991; 40(3): 292−6.
Haddad PM, Wieck A. Antipsychotic-induced hyperprolactin-aemia: mechanisms, clinical features and management. Drugs 2004; 64(20): 2291−314.
Howard L, Kirkwood G, Leese M. Risk of hip fracture in patients with a history of schizophrenia. Br J Psychiatry 2007; 190: 129−34.
Muench J, Hamer A. Adverse effects of antipsychotic medica-tions. Am Fam Physician 2010; 81(5): 617−22.
Lotinun S, Limlomwongse L, Krishnamra N. The study of a physiological significance of prolactin in the regulation of cal-cium metabolism during pregnancy and lactation in rats. Can J Physiol Pharmacol 1998; 76(2): 218−28.
Kovacs CS. Calcium and bone metabolism in pregnancy and lactation. J Clin Endocrinol Metab 2001; 86(6): 2344−8.
Lotinun S, Limlomwongse L, Sirikulchayanonta V, Krishnamra N. Bone calcium turnover, formation, and resorption in bro-mocriptine- and prolactin-treated lactating rats. Endocrine 2003; 20(1−2): 163−70.
Polatti F, Capuzzo E, Viazzo F, Colleoni R, Klersy C. Bone mineral changes during and after lactation. Obstet Gynecol 1999; 94(1): 52–6.
Karlsson C, Obrant KJ, Karlsson M. Pregnancy and lactation con-fer reversible bone loss in humans. Osteoporos Int 2001; 12(10): 828−34.
Bezerra FF, Mendonça LM, Lobato EC, Brien KO, Donangelo CM. Bone mass is recovered from lactation to postweaning in ado-lescent mothers with low calcium intakes. Am J Clin Nutr 2004; 80(5): 1322−6.
Streeten EA, Ryan KA, McBride DJ, Pollin TI, Shuldiner AR, Mitchell BD. The relationship between parity and bone mineral density in women characterized by a homogeneous lifestyle and high parity. J Clin Endocrinol Metab 2005; 90(8): 4536−41.
Lenora J, Lekamwasam S, Karlsson MK. Effects of multiparity and prolonged breast-feeding on maternal bone mineral density: a community-based cross-sectional study. BMC Womens Health 2009; 9: 19.
Cross NA, Hillman LS, Allen SH, Krause GF, Vieira NE. Cal-cium homeostasis and bone metabolism during pregnancy, lactation, and postweaning: a longitudinal study. Am J Clin Nutr 1995; 61(3): 514−23.
Ritchie LD, Fung EB, Halloran BP, Turnlund JR, Van LM, Cann CE, et al. A longitudinal study of calcium homeostasis during human pregnancy and lactation and after resumption of men-ses. Am J Clin Nutr 1998; 67(4): 693−701.
Kovacs CS, Kronenberg HM. Maternal-fetal calcium and bone me-tabolism during pregnancy, puerperium, and lactation. Endocr Rev 1997; 18(6): 832−72.
Mahadevan S, Kumaravel V, Bharath R. Calcium and bone disorders in pregnancy. Indian J Endocrinol Metab 2012; 16(3): 358−63.
Rasmussen N, Frolich A, Hornnes PJ, Hegedus L. Serum ionized calcium and intact parathyroid hormone levels during preg-nancy and postpartum. Br J Obestet Gynecol 1990; 97(9): 857−62.
Dahlman T, Sjöberg HE, Bucht E. Calcium homeostasis in nor-mal pregnancy and puerperium. A longitudinal study. Acta Obstet Gynecol Scand 1994; 73(5): 393−8.
Garner SC, Peng TC, Toverud SU. Modulation od serum parathyroid hormone and ionized calcium concentrations during reproduction in rats fed a low calcium diet. J Bone Miner Res 1988; 3(3): 319−23.
Boass A, Garner SC, Schultz VL, Toverud SU. Regulation of Se-rum Calcitriol by Serum Ionized Calcium in Rats During Preg-nancy and Lactation. J Bone Miner Res 1997; 12(6): 909−14.
Peacock M. Calcium Metabolism in Health and Disease. Clin J Am Soc Nephrol 2010; 5(Supplement 1): 23−30.
Gallacher SJ, Fraser WD, Owens OJ, Dryburgh FJ, Logue FC, Jen-kins A, et al. Changes in calciotrophic hormones and bio-chemical markers of bone turnover in normal human preg-nancy. Eur J Endocrinol 1994; 131(4): 369−74.
Cole DE, Gundberg CM, Stirk LJ, Atkinson SA, Hanley DA, Ayer LM, et al. Changing osteocalcin concentrations during preg-nancy and lactation: implications for maternal mineral metabo-lism. J Clin Endocrinol Metab 1987; 65(2): 290−4.
Cross NA, Hillman LS, Allen SH, Krause GF. Changes in bone mineral density and markers of bone remodeling during lacta-tion and postweaning in women consuming high amounts of calcium. J Bone Miner Res 1995; 10(9): 1312−20.
Hellmeyer L, Ziller V, Anderer G, Ossendorf A, Schmidt S, Hadji P. Biochemical markers of bone turnover during pregnancy: a longitudinal study. Exp Clin Endocrinol Diabetes 2006; 114(9): 506−10.
Rosenzweig P, Canal M, Patat A, Bergougnan L, Zieleniuk I, Bianchetti G. A review of the pharmacokinetics, tolerability and pharmacodynamics of amisulpride in healthy volunteers. Hum Psychopharmacol 2002; 17(1): 1−13.
Beaulieu J, Gainetdinov RR. The physiology, signaling, and phar-macology of dopamine receptors. Pharmacol Rev 2011; 63(1): 182−217.
Stojilkovic SS, Murano T, Gonzalez-Iglesias AE, Andric SA, Popovic MA, Van GF, et al. Multiple roles of Gi/o protein-coupled re-ceptors in control of action potential secretion coupling in pi-tuitary lactotrophs. Ann NY Acad Sci 2009; 1152: 174−86.
Aydin H, Mutlu N, Akbas NB. Treatment of a major depres-sion episode suppresses markers of bone turnover in premenopausal women. J Psychiatr Res 2011; 45(10): 1316−20.
Yang J, Joe S, Lee M, Ko Y, Jung I, Kim S. Effects of long-term combination treatment with valproate and atypical antipsy-chotics on bone mineral density and bone metabolism in premenopausal patients with bipolar disorder: a preliminary study. Psychiatry Investig 2011; 8(3): 256−61.
Wyszogrodzka-Kucharska A, Rabe-Jabłońska J. Calcium balance and regulation in schizophrenic patients treated with second generation antipsychotics. Psychiatr Pol 2005; 39(6): 1157−71.
Tanrattana C, Charoenphandhu N, Limlomwongse L, Krishnamra N. Prolactin directly stimulated the solvent drag-induced calcium transport in the duodenum of female rats. Biochim Biophys Acta 2004; 1665(1−2): 81−91.
Charoenphandhu N, Limlomwongse L, Krishnamra N. Prolactin di-rectly enhanced Na+/K+- and Ca2+-ATPase activities in the duodenum of female rats. Can J Physiol Pharmacol 2006; 84(5): 555−63.
Jantarajit W, Thongon N, Pandaranandaka J, Teerapornpuntakit J, Krishnamra N, Charoenphandhu N. Prolactin-stimulated transepi-thelial calcium transport in duodenum and Caco-2 monolayer are mediated by the phosphoinositide 3-kinase pathway. Am J Physiol Endocrinol Metab 2007; 293(1): 372−84.
Charoenphandhu N, Krishnamara N. Prolactin is an important regulator of intestinal calcium transport. Can J Physiol Phar-macol 2007; 85(6): 569−81.
Bataille-Simoneau N, Gerland K, Chappard D, Basle MF, Mercier L. Expression of prolactin receptors in human osteosarcoma cells. Biochem Biophys Res Commun 1996; 229(1): 323−8.
Clément-Lacroix P, Ormandy C, Lepescheux L, Ammann P, Damotte D, Goffin V, et al. Osteoblasts are a new target for prolactin: analysis of bone formation in prolactin receptor knockout mice. Endocrinology 1999; 140(1): 96−105.
Charoenphandhu N, Tudpor K, Thongchote K, Saengamnart W, Pun-theeranurak S, Krishnamra N. High-calcium diet modulates ef-fects of long term prolactin exposure on the cortical content in ovariectomized rats. Am J Physiol Endocrinol Metab 2007; 292(2): E443−52.
Herrán A, Amado JA, García-Unzueta MT, Vázquez-Barquero JL, Perera L, González-Macías J. Increased bone remodeling in first-episode major depressive disorder. Psychosom Med 2000; 62(6): 779−82.
Kahl KG, Greggersen W, Rudolf S, Stoeckelhuber BM, Bergmann-Koester CU, Dibbelt L, et al. U. Bone mineral density, bone turnover, and osteoprotegerin in depressed women with and without borderline personality disorder. Psychosom Med 2006; 60(6): 669−74.
Lee T, Chung M, Chung H, Choi J, Kim T, So H. Bone density in chronic schizophrenia with long-term antipsychotic treatment: preliminary study. Psychiatry Investig 2010; 7(4): 278−84.
