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Ghrelin and its unacylated isoform stimulate the growth of adrenocortical tumor cells via an anti-apoptotic pathway.
Am J Physiol Endocrinol Metab. 2007 Jul; 293(1):E302-9.AJ

Abstract

Ghrelin is expressed in normal human adrenocortical cells and induces their proliferation through growth hormone secretagogue receptor 1a (GHS-R1a). Consequently, it was of interest to us to determine whether acylated ghrelin and its predominant serum isoform, unacylated ghrelin, also act as factors for adrenocortical carcinoma cell growth. To examine a potential ghrelin-regulated system in adrenocortical tumors, we measured proliferative effects of acylated and unacylated ghrelin in the adrenocortical carcinoma cell lines SW-13 and NCI-H295R. We also examined the expression of ghrelin, GHS-R1a, and corticotrophin-releasing factor receptor 2 (CRF-R2). Acylated and unacylated ghrelin in the nanomolar range dose-dependently induced adrenocortical cell growth up to 200% of untreated controls, as measured by thymidine uptake and WST1 assay. The proliferative effects of acylated and unacylated ghrelin in SW-13 cells was blocked by [D-Lys(3)]growth hormone-releasing peptide 6 (GHRP6), but a CRF-R2 antagonist had no effect on unacylated ghrelin growth stimulation. Cell cycle analysis suggests that acylated and unacylated ghrelin suppress the sub-G(0)/apoptotic fraction by up to 50%. Measurement of DNA fragmentation and caspase-3 and -7 activity in SW-13 cells confirmed that acylated and unacylated ghrelin suppress apoptotic rate. SW-13 cells express preproghrelin mRNA and secrete ghrelin, and [D-Lys(3)]GHRP6 suppresses their basal proliferation rate, strongly suggesting that ghrelin could act as an auto/paracrine growth factor. Acylated and unacylated ghrelin are potential auto/paracrine factors acting through an antiapoptotic pathway to stimulate adrenocortical tumor cell growth. Unacylated ghrelin-stimulated growth is suppressed by an antagonist of GHS-R1a, suggesting either that unacylated ghrelin is acylated before its action or that ghrelin, unacylated ghrelin, and [D-Lys(3)]GHRP-6 bind to a novel receptor in these cells.

Authors+Show Affiliations

Department of Internal Medicine, Rm. Ee542, Erasmus Medical Centre, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands. p.delhanty@erasmusmc.nlNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17405826

Citation

Delhanty, P J D., et al. "Ghrelin and Its Unacylated Isoform Stimulate the Growth of Adrenocortical Tumor Cells Via an Anti-apoptotic Pathway." American Journal of Physiology. Endocrinology and Metabolism, vol. 293, no. 1, 2007, pp. E302-9.
Delhanty PJ, van Koetsveld PM, Gauna C, et al. Ghrelin and its unacylated isoform stimulate the growth of adrenocortical tumor cells via an anti-apoptotic pathway. Am J Physiol Endocrinol Metab. 2007;293(1):E302-9.
Delhanty, P. J., van Koetsveld, P. M., Gauna, C., van de Zande, B., Vitale, G., Hofland, L. J., & van der Lely, A. J. (2007). Ghrelin and its unacylated isoform stimulate the growth of adrenocortical tumor cells via an anti-apoptotic pathway. American Journal of Physiology. Endocrinology and Metabolism, 293(1), E302-9.
Delhanty PJ, et al. Ghrelin and Its Unacylated Isoform Stimulate the Growth of Adrenocortical Tumor Cells Via an Anti-apoptotic Pathway. Am J Physiol Endocrinol Metab. 2007;293(1):E302-9. PubMed PMID: 17405826.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ghrelin and its unacylated isoform stimulate the growth of adrenocortical tumor cells via an anti-apoptotic pathway. AU - Delhanty,P J D, AU - van Koetsveld,P M, AU - Gauna,C, AU - van de Zande,B, AU - Vitale,G, AU - Hofland,L J, AU - van der Lely,A J, Y1 - 2007/04/03/ PY - 2007/4/5/pubmed PY - 2007/9/14/medline PY - 2007/4/5/entrez SP - E302 EP - 9 JF - American journal of physiology. Endocrinology and metabolism JO - Am J Physiol Endocrinol Metab VL - 293 IS - 1 N2 - Ghrelin is expressed in normal human adrenocortical cells and induces their proliferation through growth hormone secretagogue receptor 1a (GHS-R1a). Consequently, it was of interest to us to determine whether acylated ghrelin and its predominant serum isoform, unacylated ghrelin, also act as factors for adrenocortical carcinoma cell growth. To examine a potential ghrelin-regulated system in adrenocortical tumors, we measured proliferative effects of acylated and unacylated ghrelin in the adrenocortical carcinoma cell lines SW-13 and NCI-H295R. We also examined the expression of ghrelin, GHS-R1a, and corticotrophin-releasing factor receptor 2 (CRF-R2). Acylated and unacylated ghrelin in the nanomolar range dose-dependently induced adrenocortical cell growth up to 200% of untreated controls, as measured by thymidine uptake and WST1 assay. The proliferative effects of acylated and unacylated ghrelin in SW-13 cells was blocked by [D-Lys(3)]growth hormone-releasing peptide 6 (GHRP6), but a CRF-R2 antagonist had no effect on unacylated ghrelin growth stimulation. Cell cycle analysis suggests that acylated and unacylated ghrelin suppress the sub-G(0)/apoptotic fraction by up to 50%. Measurement of DNA fragmentation and caspase-3 and -7 activity in SW-13 cells confirmed that acylated and unacylated ghrelin suppress apoptotic rate. SW-13 cells express preproghrelin mRNA and secrete ghrelin, and [D-Lys(3)]GHRP6 suppresses their basal proliferation rate, strongly suggesting that ghrelin could act as an auto/paracrine growth factor. Acylated and unacylated ghrelin are potential auto/paracrine factors acting through an antiapoptotic pathway to stimulate adrenocortical tumor cell growth. Unacylated ghrelin-stimulated growth is suppressed by an antagonist of GHS-R1a, suggesting either that unacylated ghrelin is acylated before its action or that ghrelin, unacylated ghrelin, and [D-Lys(3)]GHRP-6 bind to a novel receptor in these cells. SN - 0193-1849 UR - https://www.unboundmedicine.com/medline/citation/17405826/Ghrelin_and_its_unacylated_isoform_stimulate_the_growth_of_adrenocortical_tumor_cells_via_an_anti_apoptotic_pathway_ L2 - https://journals.physiology.org/doi/10.1152/ajpendo.00377.2006?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -