Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

SAGETRACK

Sign In to gain access to subscriptions and/or personal tools.
Reproductive Sciences
This Article
Right arrow Abstract Freely available
Right arrow Free Full Text (Free PDF) Free
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (4)
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Nakamura, Y.
Right arrow Articles by Rainey, W. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nakamura, Y.
Right arrow Articles by Aoki, S.
Right arrow Articles by Yewei Xing,
Right arrow Articles by Sasano, H.
Right arrow Articles by Rainey, W. E.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Metastin Stimulates Aldosterone Synthesis in Human Adrenal Cells

Yasuhiro Nakamura, MD, PhD

Department of Physiology, Medical College of Georgia, Augusta, Georgia

Satoshi Aoki

Department of Pathology, Tohoku University School of Medicine, Sendai, Japan

Yewei Xing, BS

Department of Physiology, Medical College of Georgia, Augusta, Georgia

Hironobu Sasano, MD, PhD

Department of Pathology, Tohoku University School of Medicine, Sendai, Japan

William E. Rainey, PhD

Department of Physiology, Medical College of Georgia, Augusta, Georgia, wrainey{at}mcg.edu

Kisspeptins, including metastin, are encoded by the KiSS-1 gene and play an important role in regulating the hypothalamic gonadotropin-releasing hormone (GnRH) system via G protein—coupled receptor 54 (GPR54, also called KiSS-1R). Normally, metastin (also called Kp-54) levels are quite low, except during pregnancy, when levels increase 1000-fold over those found in men and nonpregnant women. However, the potential hormonal role of metastin in the fetal and maternal circulation is unknown. In this study, the authors examine the levels of GPR54 mRNA expression in human adult and fetal adrenals using quantitative real-time reverse-transcriptase polymerase chain reaction (RT-PCR). In addition, they examine the effects of metastin on steroidogenesis and steroidogenic enzyme mRNA levels in fetal adrenal cells and in the H295R adrenocortical cell line using enzyme immunoassay and RT-PCR techniques. The authors demonstrate that GPR54 mRNA is significantly higher (50-fold) in human fetal adrenals than in adult adrenals. Immunohistochemical studies have demonstrated that the GPR54 protein is predominantly expressed in the neocortex of human fetal adrenals in the third trimester. Metastin increases aldosterone production (approximately 2-fold) in both fetal neocortex adrenal cells and H295R adrenal cells, with a maximal increase seen at 100 nM. In addition, metastin increased angiotensin II (Ang II)—stimulated aldosterone production by approximately 1.5-fold. Metastin also increased the ability of the H295R cells to metabolize exogenously added pregnenolone to aldosterone but had no effect on the expression of aldosterone synthase (CYP11B2). These results suggest that the high fetal/maternal levels of metastin seen during pregnancy may affect adrenal production of aldosterone.

Key Words: Kisspeptins • metastin • G protein—coupled receptor 54 • aldosterone • human fetal adrenal neocortex.

References

  • Rainey WE, Rehman KS, Carr BR Fetal and maternal adrenals in human pregnancy. Obstet Gynecol Clin North Am. 2004;31:817-835.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Narasaka T., Suzuki T., Moriya T., Sasano H. Temporal and spatial distribution of corticosteroidogenic enzymes immunoreactivity in developing human adrenal. Mol Cell Endocrinol. 2001;174:111-120.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Mesiano S., Jaffe RB Developmental and functional biology of the primate fetal adrenal cortex. Endocr Rev. 1997;18:378-403.[Abstract/Free Full Text]
  • Bilban M., Ghaffari-Tabrizi N., Hintermann E., et al. Kisspeptin-10, a KiSS-1/metastin-derived decapeptide, is a physiological invasion inhibitor of primary human trophoblasts. J Cell Sci. 2004;117:1319-1328.[Abstract/Free Full Text]
  • Ohtaki T., Shintani Y., Honda S., et al. Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor. Nature. 2001;411:613-617.[CrossRef][Medline] [Order article via Infotrieve]
  • Harms JF,Welch DR, Miele ME KiSS-1 metastasis suppression and emergent pathways. Clin Exp Metastasis. 2003;20:11-18.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Horikoshi Y., Matsumoto H., Takatsu Y., et al. Dramatic elevation of plasma metastin concentrations in human pregnancy: metastin as a novel placenta-derived hormone in humans. J Clin Endocrinol Metab. 2003;88:914-919.[Abstract/Free Full Text]
  • Seminara SB, Messager S., Chatzidaki EE, et al. The GPR54 gene as a regulator of puberty. N Engl J Med. 2003;349: 1614-1627.[Abstract/Free Full Text]
  • Bassett MH, Zhang Y., Clyne C., White PC, Rainey WE Differential regulation of aldosterone synthase and 11beta-hydroxylase transcription by steroidogenic factor-1. J Mol Endocrinol. 2002;28:125-135.[Abstract]
  • Rainey WE, Bird IM, Mason JI, Carr BR Angiotensin II receptors on human fetal adrenal cells. Am J Obstet Gynecol. 1992;167:1679-1685.[Web of Science][Medline] [Order article via Infotrieve]
  • Bird IM, Hanley NA, Word RA, et al. Human NCI-H295 adrenocortical carcinoma cells: a model for angiotensin-IIresponsive aldosterone secretion. Endocrinology. 1993;133: 1555-1561.[Abstract/Free Full Text]
  • Stankovic AK, Dion LD, Parker CR Jr. Effects of transforming growth factor-beta on human fetal adrenal steroid production. Mol Cell Endocrinol. 1994;99:145-151.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Saner-Amigh K., Mayhew BA, Mantero F., et al. Elevated expression of luteinizing hormone receptor in aldosterone-producing adenomas. J Clin Endocrinol Metab. 2006;91: 1136-1142.[Abstract/Free Full Text]
  • Livak KJ, Schmittgen TD Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 2001;25:402-408.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Gazdar AF, Oie HK, Shackleton CH, et al. Establishment and characterization of a human adrenocortical carcinoma cell line that expresses multiple pathways of steroid biosynthesis. Cancer Res. 1990;50:5488-5496.[Abstract/Free Full Text]
  • Rainey WE, Bird IM, Mason JI The NCI-H295 cell line: a pluripotent model for human adrenocortical studies. Mol Cell Endocrinol. 1994;100:45-50.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Muir AI, Chamberlain L., Elshourbagy NA, et al. AXOR12, a novel human G protein-coupled receptor, activated by the peptide KiSS-1. J Biol Chem. 2001;276:28969-28975.[Abstract/Free Full Text]
  • Kotani M., Detheux M.,Vandenbogaerde A., et al.The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. J Biol Chem. 2001;276:34631-34636.[Abstract/Free Full Text]
  • Janneau JL, Maldonado-Estrada J., Tachdjian G., et al. Transcriptional expression of genes involved in cell invasion and migration by normal and tumoral trophoblast cells.J Clin Endocrinol Metab. 2002;87:5336-5339.[Abstract/Free Full Text]
  • Terao Y., Kumano S., Takatsu Y., et al. Expression of KiSS-1, a metastasis suppressor gene, in trophoblast giant cells of the rat placenta. Biochim Biophys Acta. 2004;1678:102-110.[Medline] [Order article via Infotrieve]
  • Bilban M., Ghaffari-Tabrizi N., Hintermann E., et al. Kisspeptin-10, a KiSS-1/metastin-derived decapeptide, is a physiological invasion inhibitor of primary human trophoblasts. J Cell Sci. 2004;117:1319-1328.[Abstract/Free Full Text]
  • Takino T., Koshikawa N., Miyamori H., et al. Cleavage of metastasis suppressor gene product KiSS-1 protein/metastin by matrix metalloproteinases. Oncogene. 2003;22:4617-4626.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Hiden U., Bilban M., Knofler M., Desoye G. Kisspeptins and the placenta: regulation of trophoblast invasion. Rev Endocr Metab Disord. 2007;8:31-39.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Sirianni R., Mayhew BA, Carr BR, Parker CR Jr, Rainey WE Corticotropin-releasing hormone (CRH) and urocortin act through type 1 CRH receptors to stimulate dehydroepiandrosterone sulfate production in human fetal adrenal cells. J Clin Endocrinol Metab. 2005;90:5393-5400.[Abstract/Free Full Text]
  • Sirianni R., Rehman KS, Carr BR, Parker CR Jr,Rainey WE Corticotropin-releasing hormone directly stimulates cortisol and the cortisol biosynthetic pathway in human fetal adrenal cells. J Clin Endocrinol Metab. 2005;90:279-285.[Abstract/Free Full Text]
  • Smith R., Mesiano S., Chan EC, Brown S., Jaffe RB Corticotropin-releasing hormone directly and preferentially stimulates dehydroepiandrosterone sulfate secretion by human fetal adrenal cortical cells. J Clin Endocrinol Metab. 1998;83: 2916-2920.[Abstract/Free Full Text]
  • Cooper ES, Greer IA, Brooks AN Placental proopiomelanocortin gene expression, adrenocorticotropin tissue concentrations, and immunostaining increase throughout gestation and are unaffected by prostaglandins, antiprogestins, or labor. J Clin Endocrinol Metab. 1996;81:4462-4469.[Abstract]
  • Kuohung W., Kaiser UB GPR54 and KiSS-1: role in the regulation of puberty and reproduction. Rev Endocr Metab Disord. 2006;7:257-263.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Mesiano S., Coulter CL, Jaffe RB Localization of cytochrome P450 cholesterol side-chain cleavage, cytochrome P450 17 alpha-hydroxylase/17, 20-lyase, and 3 beta-hydroxysteroid dehydrogenase isomerase steroidogenic enzymes in human and rhesus monkey fetal adrenal glands: reappraisal of functional zonation. J Clin Endocrinol Metab. 1993;77:1184-1189.[Abstract]
  • Freije WA, Pezzi V., Arici A., Carr BR, Rainey WE Expression of 11 beta-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) in the human fetal adrenal. J Soc Gynecol Investig. 1997;4:305-309.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Elsheikh A., Creatsas G., Mastorakos G., Milingos S., Loutradis D., Michalas S. The renin-aldosterone system during normal and hypertensive pregnancy. Arch Gynecol Obstet. 2001;264: 182-185.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Holland OB, Mathis JM, Bird IM, Rainey WE Angiotensin increases aldosterone synthase mRNA levels in human NCI-H295 cells. Mol Cell Endocrinol. 1993;94:R9-R13.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]

Reproductive Sciences, Vol. 14, No. 8, 836-845 (2007)
DOI: 10.1177/1933719107307823
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:


Home page
 Endocr. Rev.Home page
A. E. Oakley, D. K. Clifton, and R. A. Steiner
Kisspeptin Signaling in the Brain
Endocr. Rev., October 1, 2009; 30(6): 713 - 743.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
Y. Nakamura, Y. Xing, H. Sasano, and W. E. Rainey
The Mediator Complex Subunit 1 Enhances Transcription of Genes Needed for Adrenal Androgen Production
Endocrinology, September 1, 2009; 150(9): 4145 - 4153.
[Abstract] [Full Text] [PDF]

Home page
 ReproductionHome page
R. M Reynolds, J. J Logie, A. K Roseweir, A. J McKnight, and R. P Millar
A role for kisspeptins in pregnancy: facts and speculations
Reproduction, July 1, 2009; 138(1): 1 - 7.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
Y. Nakamura, P. J. Hornsby, P. Casson, R. Morimoto, F. Satoh, Y. Xing, M. R. Kennedy, H. Sasano, and W. E. Rainey
Type 5 17{beta}-Hydroxysteroid Dehydrogenase (AKR1C3) Contributes to Testosterone Production in the Adrenal Reticularis
J. Clin. Endocrinol. Metab., June 1, 2009; 94(6): 2192 - 2198.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Free Full Text (Free PDF) Free
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (4)
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Nakamura, Y.
Right arrow Articles by Rainey, W. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nakamura, Y.
Right arrow Articles by Aoki, S.
Right arrow Articles by Yewei Xing,
Right arrow Articles by Sasano, H.
Right arrow Articles by Rainey, W. E.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?