Androgen receptor positively regulates gonadotropin-releasing hormone receptor in pituitary gonadotropes

Autor: Emily A. Witham, Shadi Shojaei, Emily V. Ho, Varykina G. Thackray, Stephanie C Bohaczuk, Genevieve E. Ryan, Jessica Cassin, Pamela L. Mellon
Rok vydání: 2021
Předmět:
0301 basic medicine
Male
Gonadotrophs
Biochemistry
Medical and Health Sciences
LHRH
Androgen
Mice
0302 clinical medicine
Endocrinology
Receptors
Promoter Regions
Genetic
GNRHR
Biological Sciences
Androgen receptor
Receptors
Androgen
Hormone receptor
Androgens
Chromatin Immunoprecipitation Sequencing
Female
Sequence Analysis
Gonadotropin-releasing hormone receptor
medicine.medical_specialty
Heterologous
030209 endocrinology & metabolism
Biology
Gonadotropic cell
Article
Cell Line
Promoter Regions
03 medical and health sciences
Gonadotrope
Endocrinology & Metabolism
Genetic
Internal medicine
medicine
Genetics
Animals
Molecular Biology
Hormone response element
Messenger RNA
Agricultural and Veterinary Sciences
Contraception/Reproduction
GnRH receptor
Neurosciences
Sequence Analysis
DNA
DNA
030104 developmental biology
Gene Expression Regulation
Pituitary
Receptors
LHRH
Zdroj: Mol Cell Endocrinol
Popis: Within pituitary gonadotropes, the gonadotropin-releasing hormone receptor (GnRHR) receives hypothalamic input from GnRH neurons that is critical for reproduction. Previous studies have suggested that androgens may regulate GnRHR, although the mechanisms remain unknown. In this study, we demonstrated that androgens positively regulate Gnrhr mRNA in mice. We then investigated the effects of androgens and androgen receptor (AR) on Gnrhr promoter activity in immortalized mouse LβT2 cells, which represent mature gonadotropes. We found that AR positively regulates the Gnrhr proximal promoter, and that this effect requires a hormone response element (HRE) half site at -159/-153 relative to the transcription start site. We also identified nonconsensus, full-length HREs at -499/-484 and -159/-144, which are both positively regulated by androgens on a heterologous promoter. Furthermore, AR associates with the Gnrhr promoter in ChIP. Altogether, we report that GnRHR is positively regulated by androgens through recruitment of AR to the Gnrhr proximal promoter.
Databáze: OpenAIRE
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