AUTHOR=Bu Shao-Yang , Zhang Yan-Yu , Zhang Xian , Li Tian-Xiu , Zheng De-Cai , Huang Ze-Xiang , Wang Qian 

TITLE=Regulation of the kiss2 promoter in yellowtail clownfish (Amphiprion clarkii) by cortisol via GRE-dependent GR pathway

JOURNAL=Frontiers in Endocrinology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.902737

DOI=10.3389/fendo.2022.902737

ISSN=1664-2392

ABSTRACT=<p>Kisspeptin plays a vital role in mediating the stress-induced reproductive regulation. Cortisol, known as a stress-related hormone, is involved in gonadal development and sexual differentiation by binding with glucocorticoid receptor (GR) to regulate the expression of <italic>kiss</italic> gene. In the present study, cortisol treatment in yellowtail clownfish (<italic>Amphiprion clarkii</italic>) showed that the expression of <italic>kiss</italic> (<italic>kiss1</italic> and <italic>kiss2</italic>) and <italic>gr</italic> (<italic>gr1</italic> and <italic>gr2</italic>) genes were increased significantly. We demonstrated that the yellowtail clownfish Kiss neurons co-express the glucocorticoid receptors in the telencephalon, mesencephalon, cerebellum, and hypothalamus. We further cloned the promoter of <italic>kiss2</italic> gene in yellowtail clownfish and identified the presence of putative binding sites for glucocorticoid receptors, estrogen receptors, androgen receptors, progesterone receptors, AP1, and C/EBP. Applying transient transfection in HEK293T cells of the yellowtail clownfish <italic>kiss2</italic> promoter, cortisol (dexamethasone) treatment was shown to enhance the promoter activities of the yellowtail clownfish <italic>kiss2</italic> gene in the presence of GRs. Deletion analysis of <italic>kiss2</italic> promoter indicated that cortisol-induced promoter activities were located between position −660 and −433 with GR1, and −912 and −775 with GR2, respectively. Finally, point mutation studies on the <italic>kiss2</italic> promoter showed that cortisol-stimulated promoter activity was mediated by one GRE site located at position −573 in the presence of GR1 and by each GRE site located at position −883, −860, −851, and −843 in the presence of GR2. Results of the present study provide novel evidence that cortisol could regulate the transcription of <italic>kiss2</italic> gene in the yellowtail clownfish <italic>via</italic> GRE-dependent GR pathway.</p>