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Metastin Stimulates Aldosterone Synthesis in Human Adrenal Cells

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Abstract

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.

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Authors and Affiliations

  1. Department of Physiology, Medical College of Georgia, 1120 15th Street, Augusta, Georgia, 30912

    Yasuhiro Nakamura MD, PhD, Yewei Xing BS & William E. Rainey PhD

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

    Satoshi Aoki & Hironobu Sasano MD, PhD

Authors
  1. Yasuhiro Nakamura MD, PhD
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  2. Satoshi Aoki
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  3. Yewei Xing BS
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  4. Hironobu Sasano MD, PhD
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  5. William E. Rainey PhD
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Corresponding author

Correspondence to William E. Rainey PhD.

Additional information

Support for this study was provided by grants from the National Institute of Health (HD11149 and DK43140 to WER).

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Nakamura, Y., Aoki, S., Xing, Y. et al. Metastin Stimulates Aldosterone Synthesis in Human Adrenal Cells. Reprod. Sci. 14, 836–845 (2007). https://doi.org/10.1177/1933719107307823

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