AMP-activated protein kinase activation reduces the transcriptional activity of the murine luteinizing hormone β-subunit gene

• Published in: Journal of Reproduction and Development Vol. 66; no. 2; pp. 97 - 104
• Main Authors: MORIYAMA, Ryutaro, IWAMOTO, Koichi, HAGIWARA, Teruki, YOSHIDA, Saishu, KATO, Takako, KATO, Yukio
• Format: Journal Article
• Language: English
• Published: Japan The Society for Reproduction and Development 2020; Japan Science and Technology Agency
• Subjects: 5-Amino-imidazole carboxamide riboside (AICAR); Aminoimidazole Carboxamide - analogs & derivatives; Aminoimidazole Carboxamide - pharmacology; AMP; AMP-activated protein kinase; AMP-activated protein kinase (AMPK); AMP-Activated Protein Kinases - metabolism; Animals; Cell Line; Deletion mutant; Follicle Stimulating Hormone, beta Subunit - genetics; Follicle Stimulating Hormone, beta Subunit - metabolism; Follicle-stimulating hormone; Glucoprivation; Glucose; Glucose metabolism; Gonadotropin-releasing hormone; Gonadotropins; Imidazole; Kinases; Luteinizing hormone; Luteinizing hormone (LH); Luteinizing Hormone, beta Subunit - genetics; Luteinizing Hormone, beta Subunit - metabolism; Malnutrition; Mice; Original; Phosphorylation; Phosphorylation - drug effects; Pituitary; Pituitary (anterior); Pituitary Gland, Anterior - drug effects; Pituitary Gland, Anterior - metabolism; Receptors, LHRH - genetics; Receptors, LHRH - metabolism; Ribonucleotides - pharmacology; Sp1 protein; Transcription activation; Transcription factors; Transcription, Genetic - drug effects; Transcription, Genetic - physiology; Luteinizing hormone (LH); Glucoprivation; AMP-activated protein kinase (AMPK); Pituitary; 5-Amino-imidazole carboxamide riboside (AICAR)
• ISSN: 0916-8818; 1348-4400
• DOI: 10.1262/jrd.2019-143

Malnutrition is one of the factors that induces reproductive disorders. However, the underlying biological processes are unclear. AMP-activated protein kinase (AMPK) is an enzyme that plays crucial role as a cellular energy sensor. In the present study, we examined the effects of AMPK activation on the transcription of the murine gonadotropin subunit genes Cga, Lhb, and Fshb, and the gonadotropin-releasing hormone receptor Gnrh-r. Real-time PCR and transcription assay using LβT2 cells demonstrated that 5-amino-imidazole carboxamide riboside (AICAR), a cell-permeable AMP analog, repressed the expression of Lhb. Next, we examined deletion mutants of the upstream region of Lhb and found that the upstream regulatory region of Lhb (–2527 to –2198 b) was responsible for the repression by AICAR. Furthermore, putative transcription factors (SP1, STAT5a, and TEF) that might mediate transcriptional control of the Lhb repression induced by AICAR were identified. In addition, it was confirmed that both AICAR and a competitive inhibitor of glucose metabolism, 2-deoxy-D-glucose, induced AMPK phosphorylation in LβT2 cells. Therefore, the upstream region of Lhb is one of the target sites for glucoprivation inducing AMPK activation. In addition, AMPK plays a role in repressing Lhb expression through the distal –2527 to –2198 b region.