PROLIFERATIVE PITUITARY LESIONS IN RATS TREATED WITH SALMON OR PORCINE CALCITONIN

被引:5
作者
BROWN, WR
FETTER, AD
VANRYZIN, RJ
LANGLOSS, JM
机构
[1] Research Pathology, Inc., New Britain
[2] Rhone-Poulenc Rorer Pharmaceutical Corporation, Collegeville
[3] Sandoz Research Institute, East Hanover
关键词
ADENOHYPOPHYSIS; ADENOCARCINOMA; ADENOMA; HORMONE; HYPERCALCEMIA; OSTEOPOROSIS; SD RATS; F344; RATS;
D O I
10.1177/019262339302100110
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Calcitonin, the serum calcium-lowering hormone, has been used in the treatment of hypercalcemia of malignancy and postmenopausal osteoporosis in humans for several years without any adverse effects. Recent studies in rats have indicated that calcitonin may be associated with morphologic effects on the pituitary. A large study was performed on 2 strains of rats, Sprague-Dawley (SD) and Fischer-344 (F-344), with 2 types of calcitonin, salmon-derived (sCT) and porcine-derived (pCT) calcitonin to evaluate possible effects on the pituitary. Sixteen groups of 42 male and 42 female SD or F-344 rats were given 0 (vehicle control), 1.25, 5.0, or 80.0 IU/kg/day of sCT or pCT, once daily, subcutaneously, for 1 yr. An increased incidence of adenomas of the adenohypophysis was observed in male SD rats at all dose levels of sCT, female SD rats given 80 IU/kg/day of sCT, male SD rats at the high dose level of pCT, and male F-344 rats at the high dose level of sCT. Also, an increased incidence of total proliferative lesions, due mostly to an increased incidence of focal hyperplasia of the pars distalis, occurred in female F-344 rats given the high dose of sCT. These pituitary proliferations were histologically similar to those that occur spontaneously, and the incidences observed were comparable to those that could occur in rats on 2-yr or lifetime studies, indicating that the injection of calcitonin had decreased the latency period.
引用
收藏
页码:81 / 86
页数:6
相关论文
共 18 条
[1]  
Azria M., The Calcitonins: Physiology and Pharmacology, (1989)
[2]  
PMcL B., Hsu D.W., Klibanski A., Kliman B., Jameson L., Ridgway E.C., Hedley-White W., Zervas N.T., Hormone production in clinically nonfunctioning pituitary adenomas, J. Neurosurg, 66, pp. 244-250, (1987)
[3]  
Boorman G.A., Heersche J.N.M., Hollander C.F., Transplantable calcitonin-secreting medullary carcinomas of the thyroid in the WAG/Rij rat, J. Natl. Cancer Inst, 53, 4, pp. 1011-1015, (1974)
[4]  
Furth J., Clifton K.H., Experimental Pituitary Tumors, The Pituitary Gland, 2, pp. 460-497, (1966)
[5]  
Furth J., Ueda G., Clifton K.H., The pathophysiology of pituitaries and their tumors: Methodological advances, Methods in Cancer Research, 10, pp. 201-277, (1973)
[6]  
Griffith R.W., Carcinogenic potential of marketed drugs, J. Clin. Res. Drug Dev, 2, pp. 141-144, (1988)
[7]  
Jameson J.L., Weiss J., Polak J.M., Childs G.V., Bloom S.R., Steel J.H., Capen C.C., Prentice D.E., Fetter A.W., Langloss J.M., Glycoprotein hormone alpha-subunit producing pituitary adenomas in rats treated for one year with calcitonin, Am. J. Pathol, 140, 1, pp. 75-84, (1992)
[8]  
Osamura R.Y., Pituitary tumors induced by estrogen, rat, In: Monographs on Pathology of Laboratory Animals, 1, (1983)
[9]  
Kovacs K., Use G., Ryan N., McComb D.J., Horvath E., Chen H.J., Walfish P.G., Pituitary prolactin cell hyperplasia, Hormone Res, 12, 2, pp. 87-95, (1980)
[10]  
Lee A.K., DeLellis R.A., Blount M., Nunnemacher G., Wolfe H.J., Pituitary proliferative lesions in aging male Long-Evans rats, Lab. Invest, 47, 6, pp. 595-602, (1982)