SVIBOR - Project code: 3-01-030

MINISTRY OF SCIENCE AND TECHNOLOGY

Strossmayerov trg 4, HR - 10000 ZAGREB
tel.: +385 1 459 44 44, fax: +385 1 459 44 69
E-mail: ured@znanost.hr

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Project code: 3-01-030


MORPHOLOGICAL AND FUNCTIONAL CHARACTERISTICS OF PITUITARY ADENOMAS


Main researcher: KORŠIĆ, MIRKO (81592)


Assistants
Type of research: basic
Duration from: 01/01/91. to 12/31/95.
Papers on project (total): 23
Papers on project quoted in Current Contents: 2
Institution name: Medicinski fakultet, Zagreb (108)
Department/Institute: Division of endocrinology and metabolism Department of internal medicine Rebro, School of medicine University of Zagreb
Address: Kišpatićeva 12, Zagreb, Croatia
City: 10000 - Zagreb, Croatia
Communication
Phone: 385 (0) 1 22 31 80
Phone: 385 (0) 1 21 72 80
Phone: 385 (0) 1 233 32 33 (301,220)
Fax: 385 (0) 1 21 72 80
Summary: Ninety six patients with pituitary adenomas were treated in the Division of Endocrinology and Metabolism (62 reported previously; 36 new cases). Most nonfunctioning adenomas (NFA) were null cell adenomas on electron microscopy (EM) (52/55), and on immunohistochemistry (IHC) gonadotropins or their á-subunits were proved. Only several tumours were weakly positive on other pituitary hormones (STH, PRL, ACTH). We added endothelin-3 (ET3) or "bioactive raction of the human plasma ultrafiltrate" (TBP) to tumour tissue culture (TTC). TBP was isolated from l l of plasma and purified on ion exchanger columns. According to ACTH level in the TTC medium we divided the tumours in two groups: 1. tumours which secreted to the TTC medium more than 200 ng/L of ACTH; after incubation with TBP significant inhibition of ACTH secretion occured; 2. tumours which secreted less than 200 ng/L ACTH to the medium, and after the incubation with TBP significant stimulation of ACTH secretion occured. These findings significantly correlated with the results of IHC. Also, significant negative correlation of basal secretotry activity of ACTH and its secretory activity after TBP addition was found. Such effects were not found in adenomas which have incorporated tissue of healthy pituitary gland. With addition of ET3 to the TTC medium, the secretion of PRL, STH, LH and FSH was reduced. The level of ACTH was changed depending on the basal level of this hormone in the medium without addition of ET3. In the cultures of tumours which secreted more than 300 ng/L ACTH, the addition of ET3 has reduced its level, while when ACTH level was basally under this value, the addition of ET3 increased it. Endogenous ET3 was detected in about half of the adenoma samples.

Keywords: Pituitary adenoma, nonfunctioning adenomas, immunohistochemistry, electron microscopy, adenomas' tissue culture, pituitary hormones, adenomas' secretory activity, gonadotropins, "bioactive fraction of the human plasma ultrafiltrate" (TBP), endothelin-3.

Research goals: According to the hormonal activity in vivo, pituitary adenomas can be divided in nonsecreting tumours (clinically characterized with different degree of hypopituitarism) and those associated with hormone hypersecretion (characterized with typical clinical features: syndrome of gallactorhea-ammenorhea, acromegaly, Cushing,s disease). The use of in vitro TTC and the comparison of the features of the cultured tumours with their behaviour in vivo, revealed their variability of morphological features and hormone secreting activity. Such analyses of the characteristics of pituitary tumours made a basis for the research of the activity of factors that might be involved in the regulation of the tumour behaviour. However, dependency of the adenoma cells on the control of the neuroendocrine system is uncertain, while the nature of factors that might be involved in the regulation of hormone secreting activity of pituitary adenomas is unknown. Tumours associated with clinical evidence of hormone excess show high hormone secreting activity if cultured in vitro, but NFA could in culture exert hormone secreting activity, at lower extent, too. Most of them secrete gonadotropins and their subunits, but some of them release other pituitary hormones (STH, PRL, ACTH), as well. Hence, it seems that the secretory activity of the pituitary tumours could be influenced by regulatory mechanisms (systemic?), probably mediated by hypothalamic and humoral factors. We wanted to evaluate how ET3, and TBP whose nature is not defined yet (it can be similar to the growth modifying factor that was found as heat and acid resistant component in different tissues and culture media), influence the pituitary adenomas in vitro. The further task would be to analyse the nature of TBP, to evaluate its effects on the control of hormone release from the normal pituitary gland, as well as on the growth features of the normal and the pituitary tumour cells.

COOPERATION - PROJECTS


  1. Name of project: 3-01-082 NEUROTRANSMITERI U REGULACIJI ADENOHIPOFIZE
    Name of institution: Zavod za endokrinologiju i bolesti metabolizma, Interna klinika Medicinskog fakulteta KBC REBRO
    City: 10000 - Zagreb, Croatia

COOPERATION - INSTITUTIONS


  1. Name of institution: INSTITUT "RUĐER BOŠKOVIĆ"
    Type of institution: State institute
    Type of cooperation: Joint publishing of scientific papers
    City: 10000 - Zagreb, Croatia
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