SOMATOSTATIN REGULATION OF GLYCOPROTEIN HORMONE AND FREE SUBUNIT SECRETION IN CLINICALLY NONFUNCTIONING AND SOMATOTROPH ADENOMAS INVITRO

被引:36
作者
KLIBANSKI, A
ALEXANDER, JM
BIKKAL, HA
HSU, DW
SWEARINGEN, B
ZERVAS, NT
机构
[1] MASSACHUSETTS GEN HOSP, DEPT NEUROSURG, BOSTON, MA 02114 USA
[2] MASSACHUSETTS GEN HOSP, DEPT PATHOL, BOSTON, MA 02114 USA
关键词
D O I
10.1210/jcem-73-6-1248
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
There is increasing evidence that clinically non-functioning pituitary tumors produce and secrete glycoprotein hormone and/or free alpha- and beta-subunits. In addition, hypersecretion of free alpha-subunit occurs in up to 37% of patients with somatotroph adenomas. An understanding of glycoprotein hormone regulation is important in developing effective therapeutic strategies for patients with tumors associated with intact glycoprotein hormone and free subunit hypersecretion. We investigated glycoprotein hormone and free subunit secretion by somatostatin in primary dispersed cultures of pituitary tumor cells from 23 patients with pituitary adenomas. Fifteen tumors from patients with clinically nonfunctioning adenomas (group 1) and 8 tumors from patients with somatotroph adenomas and cosecretion of alpha-subunit (group 2) were studied. Cultures were incubated with control or somatostatin-supplemented media for 24 h. Media samples from group 1 tumors were assayed for intact glycoprotein hormones and free alpha- and beta-subunits secretion levels, while media samples from group 2 cultures were assayed for alpha-subunit and GH secretion levels. Significant (P < 0.05-0.001) inhibition of secretion of 1 or more intact hormones and/or free subunits was found in 10 of the 15 group 1 tumors. SRIF[10(-7) M] suppressed intact gonadotropin secretion in 60% of FSH-producing tumors and 30% of LH-producing tumors. Media concentrations of FSH-beta and LH-beta were decreased in 31% and 50% of group 1 tumors, respectively, following somatostatin treatment in those tumors which secreted free beta-subunits. alpha-Subunit was secreted by 12 of the 15 tumors, but significant (P < 0.02-0.01) inhibition by somatostatin was observed in only 2 tumors. In contrast, significant (P < 0.05-0.001) inhibition of alpha-subunit in the somatotroph adenomas was found in 6 of the 8 tumors. Significant decreases in alpha-subunit were observed only in those tumors where GH was also significantly inhibited by somatostatin. We conclude that 1) somatostatin inhibits intact glycoprotein or free subunit secretion in the majority of clinically nonfunctioning pituitary tumors in vitro and 2) alpha-subunit secretion is suppressed in 17% and 69% of clinically nonfunctioning and somatotroph adenomas, respectively, consistent with a differential regulation of alpha-subunit by somatostatin in these two tumor types.
引用
收藏
页码:1248 / 1255
页数:8
相关论文
共 36 条
[1]   TREATMENT OF INAPPROPRIATE SECRETION OF THYROTROPIN WITH SOMATOSTATIN ANALOG SMS-201-995 [J].
BECKPECCOZ, P ;
MEDRI, G ;
PISCITELLI, G ;
MARIOTTI, S ;
BERTOLI, A ;
BARBARINO, A ;
RONDENA, M ;
MARTINO, E ;
PINCHERA, A ;
FAGLIA, G .
HORMONE RESEARCH, 1988, 29 (2-3) :121-123
[2]   GLYCOPROTEIN HORMONE ALPHA-SUBUNIT RESPONSE TO GROWTH-HORMONE (GH)-RELEASING HORMONE IN PATIENTS WITH ACTIVE ACROMEGALY - EVIDENCE FOR ALPHA-SUBUNIT AND GH COEXISTENCE IN THE SAME TUMORAL CELL [J].
BECKPECCOZ, P ;
BASSETTI, M ;
SPADA, A ;
MEDRI, G ;
AROSIO, M ;
GIANNATTASIO, G ;
FAGLIA, G .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1985, 61 (03) :541-546
[3]   HORMONE PRODUCTION IN CLINICALLY NONFUNCTIONING PITUITARY-ADENOMAS [J].
BLACK, PM ;
HSU, DW ;
KLIBANSKI, A ;
KLIMAN, B ;
JAMESON, JL ;
RIDGWAY, EC ;
HEDLEYWHYTE, ET ;
ZERVAS, NT .
JOURNAL OF NEUROSURGERY, 1987, 66 (02) :244-250
[4]  
BODEN G, 1967, DIABETOLOGIA, V3, P431
[5]   RESPONSE OF THYROTROPIN-SECRETING PITUITARY-ADENOMAS TO A LONG-ACTING SOMATOSTATIN ANALOG [J].
COMI, RJ ;
GESUNDHEIT, N ;
MURRAY, L ;
GORDEN, P ;
WEINTRAUB, BD .
NEW ENGLAND JOURNAL OF MEDICINE, 1987, 317 (01) :12-17
[6]   PITUITARY AND EXTRA-PITUITARY EFFECTS OF SOMATOSTATIN IN NORMAL MAN [J].
COPINSCHI, G ;
LECLERCQMEYER, V ;
VIRASORO, E ;
LHERMITE, M ;
VANHAELST, L ;
GOLSTEIN, J ;
LECLERCQ, R ;
FERY, F ;
ROBYN, C .
HORMONE AND METABOLIC RESEARCH, 1976, 8 (03) :226-231
[7]   SOMATOSTATIN LOWERING OF LH LEVELS IN A POSTMENOPAUSAL WOMAN [J].
CURNOW, RT ;
TAYLOR, AM ;
CAREY, RM ;
JOHANSON, A ;
MURAD, F .
SOUTHERN MEDICAL JOURNAL, 1977, 70 (07) :871-871
[8]  
DEMURA R, 1986, J CLIN ENDOCR METAB, V63, P564
[9]  
HSU DW, 1989, AM J PATHOL, V135, P329
[10]   SPECIFIC SOMATOSTATIN RECEPTORS ON HUMAN PITUITARY-ADENOMA CELL-MEMBRANES [J].
IKUYAMA, S ;
NAWATA, H ;
KATO, K ;
KARASHIMA, T ;
IBAYASHI, H ;
NAKAGAKI, H .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1985, 61 (04) :666-671