*Corresponding author:Kenji Ohe, Department of Pharmacotherapeutics, Faculty of Pharmaceutical Sciences, Fukuoka University, Japan
Received: July 12, 2018; Published: July 23, 2018
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The relationship between circadian rhythm and autonomous cortisol secretion of adrenocortical lesions associated with Cushing’s syndrome is still unknown. We show here that in Y1 adrenocortical tumor cells, circadian rhythm of Per2 mRNA expression was in a 24 h manner, while that of steroidogenic-related genes such as P450scc mRNA and Ad4BP/SF-1 mRNA was asynchronous with Per 2 mRNA, compared to normal mouse adrenal primary culture tissue which show synchronized expression of the three genes. Deletion mutants of Ad4BP/SF-1 promoter activity in Y1 cells show that the E-box element functioned in a circadian-like pattern which was abrogated in promoter constructs which lack the E-box. Rhythm of upstream factor-1 (USF-1) mRNA correlated with Ad4BP/SF-1 mRNA expression, which is known to bind the E-box of Ad4BP/SF-1 promoter. Finally, we were able to detect asynchronous rhythm of P450scc, Ad4BP/SF-1 compared with Per2 promoter activity in primary cultured cells derived from adrenocortical lesions associated with Cushing’s syndrome. We believe the results presented here a result of tumorigenesis rather than evoking it, but we are certain that the method used here will provide us tools in deciphering the mechanism of tumorigenesis. Thus, we conclude asynchronous expression of Ad4BP/SF-1 and Per2 is in part related to the pathogenesis in adrenocortical lesions of Cushing’s syndrome.
Keywords: Ad4BP/SF-1; Circadian Rhythm; Adrenal Tumor; Cushing’s Syndrome; Tumorigenesis; Steroidogenic; Pathogenesis; Pituitary Gland; Parvocellular Neurons; Hyperplasia
Abbreviations: AD4BP: Adrenal 4 Binding Protein; CREM: Camp Response Element Modulator; DMEM: Dulbecco’s Modified Eagle’s Medium; ERK: Extracellular Signal Regulated Kinase; MAPK: Mitogen Activated Protein Kinase; PKA: Protein Kinase A; Per2; Period Homolog 2; RT-PCR: Reverse Transcriptase-Polymerase Chain Reaction; SF-1: Steroidogenic Factor 1; USF: Upstream Stimulatory Factor; GNAS: Gene coding for the stimulatory G-protein α subunit; AIMAH, adrenocorticotropin-independent macronodular Adrenocortical Hyperplasia; PRKAR1A: Protein Kinase Camp Dependent Regulatory Type I α Gene: PPNAD: Primary Pigmented Nodular Adrenocortical Disease