Functional in vitro studies on the role and regulation of interleukin-6 in human somatotroph pituitary adenomas

Jan Oliver Thiele, Penny Lohrer, Ludwig Schaaf, Manuela Feirer, Walter Stummer, Marco Losa, Manfred Lange, Maria Tichomirowa, Eduardo Arzt, Günter K. Stalla, Ulrich Renner

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

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-β1, insulin-like growth factor-I, pituitary adenylate cyclase-activating peptide and oestradiol) were heterogeneous in the different adenomas. Only transforming growth factor-α 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.

Original languageEnglish
Pages (from-to)455-461
Number of pages7
JournalEuropean Journal of Endocrinology
Volume149
Issue number5
DOIs
Publication statusPublished - Nov 2003

Fingerprint

Growth Hormone-Secreting Pituitary Adenoma
Pituitary Neoplasms
Interleukin-6
Adenoma
Transforming Growth Factors
In Vitro Techniques
Cell Culture Techniques
Primary Cell Culture
Octreotide

ASJC Scopus subject areas

  • Endocrinology

Cite this

Functional in vitro studies on the role and regulation of interleukin-6 in human somatotroph pituitary adenomas. / Thiele, Jan Oliver; Lohrer, Penny; Schaaf, Ludwig; Feirer, Manuela; Stummer, Walter; Losa, Marco; Lange, Manfred; Tichomirowa, Maria; Arzt, Eduardo; Stalla, Günter K.; Renner, Ulrich.

In: European Journal of Endocrinology, Vol. 149, No. 5, 11.2003, p. 455-461.

Research output: Contribution to journalArticle

Thiele, JO, Lohrer, P, Schaaf, L, Feirer, M, Stummer, W, Losa, M, Lange, M, Tichomirowa, M, Arzt, E, Stalla, GK & Renner, U 2003, 'Functional in vitro studies on the role and regulation of interleukin-6 in human somatotroph pituitary adenomas', European Journal of Endocrinology, vol. 149, no. 5, pp. 455-461. https://doi.org/10.1530/eje.0.1490455
Thiele, Jan Oliver ; Lohrer, Penny ; Schaaf, Ludwig ; Feirer, Manuela ; Stummer, Walter ; Losa, Marco ; Lange, Manfred ; Tichomirowa, Maria ; Arzt, Eduardo ; Stalla, Günter K. ; Renner, Ulrich. / Functional in vitro studies on the role and regulation of interleukin-6 in human somatotroph pituitary adenomas. In: European Journal of Endocrinology. 2003 ; Vol. 149, No. 5. pp. 455-461.
@article{da65e2ff35f149048b59a9d61833366a,
title = "Functional in vitro studies on the role and regulation of interleukin-6 in human somatotroph pituitary adenomas",
abstract = "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-β1, insulin-like growth factor-I, pituitary adenylate cyclase-activating peptide and oestradiol) were heterogeneous in the different adenomas. Only transforming growth factor-α 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.",
author = "Thiele, {Jan Oliver} and Penny Lohrer and Ludwig Schaaf and Manuela Feirer and Walter Stummer and Marco Losa and Manfred Lange and Maria Tichomirowa and Eduardo Arzt and Stalla, {G{\"u}nter K.} and Ulrich Renner",
year = "2003",
month = "11",
doi = "10.1530/eje.0.1490455",
language = "English",
volume = "149",
pages = "455--461",
journal = "European Journal of Endocrinology",
issn = "0804-4643",
publisher = "BioScientifica Ltd.",
number = "5",

}

TY - JOUR

T1 - Functional in vitro studies on the role and regulation of interleukin-6 in human somatotroph pituitary adenomas

AU - Thiele, Jan Oliver

AU - Lohrer, Penny

AU - Schaaf, Ludwig

AU - Feirer, Manuela

AU - Stummer, Walter

AU - Losa, Marco

AU - Lange, Manfred

AU - Tichomirowa, Maria

AU - Arzt, Eduardo

AU - Stalla, Günter K.

AU - Renner, Ulrich

PY - 2003/11

Y1 - 2003/11

N2 - 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-β1, insulin-like growth factor-I, pituitary adenylate cyclase-activating peptide and oestradiol) were heterogeneous in the different adenomas. Only transforming growth factor-α 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.

AB - 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-β1, insulin-like growth factor-I, pituitary adenylate cyclase-activating peptide and oestradiol) were heterogeneous in the different adenomas. Only transforming growth factor-α 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.

UR - http://www.scopus.com/inward/record.url?scp=0344465980&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0344465980&partnerID=8YFLogxK

U2 - 10.1530/eje.0.1490455

DO - 10.1530/eje.0.1490455

M3 - Article

C2 - 14585094

AN - SCOPUS:0344465980

VL - 149

SP - 455

EP - 461

JO - European Journal of Endocrinology

JF - European Journal of Endocrinology

SN - 0804-4643

IS - 5

ER -