Asynchronous Rhythm of Ad4BP/SF-1 and Per2 Expression in Adrenal Tumors of Cushing’s Syndrome

Kenji Ohe

doi:10.26717/bjstr.2018.07.001459

Abstract

Asynchronous Rhythm of Ad4BP/SF-1 and Per2 Expression in Adrenal Tumors of Cushing’s Syndrome

Highlights

The primary adrenal form of Cushing’s syndrome is characterized by ACTH-independent autonomous cortisol secretion from adrenocortical tumors with diminished diurnal rhythm
In order to address whether adrenal tumors possess intrinsic circadian rhythm of de novo steroid hormone synthesis, tissues and cells were stimulated with serum shock for 2h and steroid hormones were measured every 4h thereafter (Figure 1)
Per2 as well as Ad4BP/Steroidogenic Factor 1 (SF-1), P450scc genes did respond to serum shock in adrenal tumor-derived cells but these cells could not produce steroid in a circadian fashion

Summary

Introduction

The primary adrenal form of Cushing’s syndrome is characterized by ACTH-independent autonomous cortisol secretion from adrenocortical tumors with diminished diurnal rhythm. The normal adrenal gland produces cortisol stimulated by rhythmic secretion of ACTH from the pituitary gland driven by CRH secretion from parvocellular neurons of the paraventricular nucleus of the hypothalamus. Circadian circuits stimulate suprachiasmatic nucleus (SCN) afferents which stimulate CRH secretion [1,2]. In addition to this hypothalamus pituitary adrenal (HPA) axis activity, the peripheral clock of the adrenal gland is known to be activated by light via the suprachiasmatic nucleus-sympathetic nervous system in the absence of ACTH [3]. Together with activating mutations of the gene coding for the stimulatory G protein α subunit (GNAS) in adrenocorticotropin independent macronodular adrenocortical hyperplasia (AIMAH) [5] and mutations of protein kinase, Camp dependent, regulatory, type I, α gene (PRKAR1A) in primary pigmented nodular adrenocortical disease (PPNAD), and other accumulating evidence has endorsed the idea that adrenocortical lesions of Cushing’s syndrome harbor abnormalities of the cyclic AMP signaling pathway [6]

Methods

Results

Conclusion