Growth Hormone Deficiency Impairs Blood Clotting and Reduces Factor VII Coagulant Activity in Rat

Summary

To investigate pituitary effects on the vitamin K-dependent coagulation factors, female rats were hypophysectomized (hypox) and treated with growth hormone (GH), cortisone, thyroxine, vitamin K, or saline. After 11 days of treatment, the prothrombin time, platelet count, and factors II, VII, IX, and X were determined. The prothrombin time was 52.9 ± 1.2% for control rats and 39.1 ± 0.8% for hypox rats (mean ± SEM; p<0.001). All factors decreased after hypophysectomy, reaching significance for factor VII (from 264 ± 23% to 131 ± 9%; p <0.001) and factor IX (from 28.4 ± 2.2% to 17.1 ± 2.5%; p<0.01) while the platelet count was unaffected. When hypox rats were treated with GH, the prothrombin time increased to 50.9 ± 1.0% (p <0.001) and factor VII to 299 ± 10% (p<0.001). Factor II, IX, and X were slightly increased after GH substitution but not after cortisone, thyroxine, or vitamin K treatment. To summarize, GH is of importance for normal hemostasis in the female rat.

• References

• 1 Jørgensen JO, Pedersen SA, Ingerslev J, Möler J, Skakkebok NE, Christiansen S. Growth hormone (GH) therapy in GH-deficient patients the plasma factor Vlll-von Willebrand factor complex and capillary fragility. A double-blind, placebo-controlled crossover study Scand J Clin Lab Invest 1990; 50: 417-420
• 2 Borkenstein M, Muntean WR. Effects of growth hormone on the factor VIII complex in patients with growth hormone deficiency. Metabolism 1984; 33: 1065-1067
• 3 Ingerslev J, Christensen PD, Stenbjerg S, Møller N, Ørskov H, Christiansen JS. Diabetes-like alterations in haemostatic parameters after one week’s growth hormone administration in normal man. J Diabetic Complications 1989; 3: 103-106
• 4 Gustafsson J-Å, Edén S, Eneroth P, Hökfelt T, Isaksson O, Jansson J-O, Mode A, Norstedt G. Regulation of sexually dimorphic hepatic steroid metabolism by the somatostatin-growth hormone axis. J Steroid Biochem 1983; 19: 691-698
• 5 Eriksson L, Carlsson-Bostedt L, Oscarsson J, Edén S, Stigbrand T, von Schoultz B. Secretory pattern of growth hormone regulates plasma concentration of pregnancy- associated murine protein-1 in the non-pregnant rat. J Reprod Fert 1988; 84: 111-6
• 6 Jansson J-O, Oscarsson J, Mode A, Ritzén EM. Plasma growth hormone pattern and androgens influence the levels of corticosteroid-binding globulin in rat serum. J Endocrinol 1989; 122: 725-732
• 7 Jeffery S, Carter ND, Clark RG, Robinson IC A F. The episodic secretory pattern of growth hormone regulates liver carbonic anhydrase III. Biochem J 1990; 266: 69-74
• 8 Schlechter NL, Russell SM, Greenberg S, Spencer EM, Nicoll CS. A direct growth effect of growth hormone in rat hindlimb shown by arterial infusion. Am J Physiol 1986; 250: E231-E235
• 9 Theeuwes F, Yum SI. Principles of the design and operation of generic osmotic pumps for the delivery of semisolid or liquid drug formulations. Ann Biomed Eng 1976; 4: 343-356
• 10 Gordon EM, Hellerstein HK, Ratnoff OD, Arafah BM, Yamashita TS. Augmented Hageman factor and prolactin titers, enhanced cold activation of factor VII, and spontaneous shortening of prothrombin time in survivors of myocardial infarction. J Lab Clin Med 1987; 109: 409-413
• 11 Lundboek K, Christensen NJ, Jensen VA. Diabetes, diabetic angiopathy, and growth hormone. Lancet 1970; 2: 131-133
• 12 Christiansen NJ, Terkilsen AB. Quantitative measurements of skin capillary resistance in hypophysectomized long-term diabetics. Diabetes 1971; 20: 297-301
• 13 Edén S. Age- and sex related differences in episodic growth hormone secretion in the rat. Endocrinology 1979; 105: 555-560
• 14 Engström KG, Ohlsson L, Oscarsson J. Effect of hypophysectomy and growth hormone substitution on red blood cell morphology and filterability in rats. J Lab Clin Med 1990; 116: 196-205
• 15 Mosher DF. Blood coagulation and fibrinolysis: An overview. Clin Cardiol 1990; 13 (06) 5-11
• 16 Porta M, Maneschi F, White MC, Kohner EM. Twenty-five hour variations of von Willebrand factor and factor VIII-related antigen in diabetic retinopathy. Metabolism 1981; 695-699
• 17 Hart A, Cohen H. Capillary fragility studies in diabetes. Brit Med J 1969; 2: 89-91
• 18 Postel-Vinay M-C. Binding of human growth hormone to rat liver membranes: lactogenic and somatotropic sites. FEBS letter 1976; 68: 137-140
• 19 Mathews S, Enberg B, Norstedt G. Regulation of rat growth hormone receptor gene expression. J Biol Chem 1989; 264: 9905-9910
• 20 Maiter D, Underwood LE, Maes M, Davenport ML, Ketelslegers JM. Different effects of intermittent and continuous growth hormone (GH) administration on serum somatomedin-C/insulin-like growth factor I and liver GH receptors in hypophysectomized rats. Endocrinology 1988; 123: 1053-1059
• 21 Oscarsson J. Growth hormone regulation of serum lipoproteins in the rat. Thesis, University of Göteborg; Sweden: 1990. pp 1-43
• 22 D’Ercole AJ, Stiles AD, Underwood LE. Tissue concentrations of somatomedin C. Further evidence for multiple sites of synthesis and paracrine mechanisms of action. Proc Natl Acad Sci 1984; 81: 935-939
• 23 Ekberg S, Carlsson L, Carlsson B, Billig H, Jansson J-O. Plasma growth hormone pattern regulates epidermal growth factor (EGF) receptor messenger ribonucleic acid levels and EGF binding in the rat liver. Endocrinology 1989; 125: 2158-2166
• 24 Mann KG, Nesheim ME, Church P, Haley P, Krishnaswamy S. Surface-dependent reactions of the vitamin K-dependent enzyme complexes. Blood 1990; 76: 1-16
• 25 Chemausek SD, Underwood LE, van WykJ. Influence of hypothyroidism on growth hormone binding by rat liver. Endocrinology 1982; 111: 1534-1538
• 26 Primrose JN, Davies JA, Prentice CR M, Hughes R, Johnston D. Reduction in factor VII, fibrinogen and plasminogen activator inhibitor-1 activity after surgical treatment of morbid obesity. Thromb Haemost 68: 396-399
• 27 Folsom AR, Qamhieh HT, Wing RR, Jeffery RW, Stinson VL, Kuller LH, Wu KK. Impact of weight loss and plasminogen activator inhibitor (PAI-I), factor VII, and other hemostatic factors in moderately overweight adults. Arteriosclerosis 1993; 13: 162-169
• 28 Miller G J. Hemostasis and cardiovascular risk. The British and European experience Arch Pathol Lab Med 1992; 116: 1318-1321
• 29 Scarabin PY, Bonithon-Kopp C, Bara L, Malmejac A, Guize L, Samama M. Factor VII activation and menopausal status. Thromb Res 1990; 57: 227-234
• 30 Schulman S, Johnsson H, Lindmarker P. Thrombotic complications after substitution with a FVII concentrate. Thromb Haemost 1991; 66: 619
• 31 Bengtsson BÅ, Edén S, Ernest I. Epidemiology and long-term survival in acromegaly A study of 166 cases diagnosed between 1955 and 1984. Acta Med Scand 1988; 223: 327-35
• 32 Wright AD, Hill DM, Lowy C. Mortality in acromegaly. Q J Med 1970; 39: 1-16