Functional in vitro studies on the role and regulation of interleukin-6 in human somatotroph pituitary adenomas.
OBJECTIVE
Interleukin-6 (IL-6), a member of the gp130 cytokine family, is considered to be an important modulator of function and growth in endocrine anterior pituitary cells. In pituitary adenomas, where IL-6 is often produced by the tumour cells, it is thought to be involved in pituitary adenoma pathophysiology via autocrine/paracrine mechanisms.


METHODS
We have studied in primary cell cultures of human somatotroph adenomas whether IL-6 stimulates growth hormone secretion and whether intratumoral IL-6 is affected by various IL-6-regulating factors.


RESULTS
Interleukin-6 stimulated GH secretion in 10 out of 11 somatotroph adenoma cultures (1.4- to 6.5-fold above basal levels). In comparative studies the GH-stimulatory potency of IL-6 was identical, or even stronger, than that of GHRH. In eight out of 11 adenoma cell cultures, IL-6 production was observed. This suggests that GH production might be stimulated by IL-6 in an autocrine/paracrine manner in these tumours. Dexamethasone strongly inhibited basal IL-6 secretion in all IL-6-producing adenoma cell cultures, whereas the IL-6 inhibitory or stimulatory action of other factors (octreotide, transforming growth factor-beta1, insulin-like growth factor-I, pituitary adenylate cyclase-activating peptide and oestradiol) were heterogeneous in the different adenomas. Only transforming growth factor-alpha consistently stimulated IL-6 secretion in all of the adenomas studied.


CONCLUSIONS
Intratumoral IL-6, which is differently regulated by various factors, might contribute to excessive GH production in the majority of somatotroph adenomas.
Thiele
Jan-Oliver
JO
Max-Planck-Institute of Psychiatry, Department of Endocrinology, Kraepelinstr. 10, D-80804 Munich, Germany.
Lohrer
Penny
P
Schaaf
Ludwig
L
Feirer
Manuela
M
Stummer
Walter
W
Losa
Marco
M
Lange
Manfred
M
Tichomirowa
Maria
M
Arzt
Eduardo
E
Stalla
Günter K
GK
Renner
Ulrich
U
D000236:Adenoma / Q000378:metabolism*; D000276:Adjuvants, Immunologic / Q000378:metabolism / Q000494:pharmacology; D000328:Adult; D004305:Dose-Response Relationship, Drug; D005260:Female; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D015850:Interleukin-6; D019382:Human Growth Hormone