Transcriptome Profiling Reveals Differentially Expressed Transcripts Between the Human Adrenal Zona Fasciculata and Zona Reticularis

Abstract

Microarray results demonstrated that only 347 transcripts of the 47 231 were significantly different by 2-fold or greater in the ZF and ZR. ZF had 195 transcripts with 2-fold or greater increase compared with its paired ZR, whereas ZR was found to have 152 transcripts with 2-fold or greater higher expression than in ZF. Microarray and qPCR analysis of transcripts encoding steroidogenic enzymes (n = 10) demonstrated that only 3β-hydroxysteroid dehydrogenase, steroid sulfotransferase, type 5 17β-hydroxysteroid dehydrogenase, and cytochrome b5 were significantly different. Immunohistochemistry and qPCR studies confirmed that the ZF had an increased expression of lymphoid enhancer-binding factor 1 and nephroblastoma overexpressed, whereas ZR showed an increased expression of solute carrier family 27 (fatty acid transporter) (SLC27A2), member 2 and TSPAN12 (tetraspanin 12) CONCLUSION: Microarray revealed several novel candidate genes for elucidating the molecular mechanisms governing the ZF and ZR, thereby increasing our understanding of the functional zonation of these two adrenocortical zones.

60 YEARS OF POMC: Adrenal and extra-adrenal functions of ACTH

“…All the above effects of ACTH have been confirmed by measurements of gene expression (Xing et al 2011, Nishimoto et al 2012, Rege et al 2014. In this regard, the Y1 mouse adrenocortical cell line is a model that has been widely used to identify changes in gene expression after treatment with ACTH.…”

PKA signaling drives reticularis differentiation and sexually dimorphic adrenal cortex renewal

“…qPCR analysis also revealed increased expression of Sult1e1, which can be involved in DHEA sulfation (26) (Figure 2D). Taken together, decreased expression of HSD3B (HSD3B2 in humans, HSD3B1 in mice), expression of CYP17 and CYB5 (its allosteric regulator), and expression of the potential for steroid sulfation are reminiscent of the human zR (5,(27)(28)(29)(30)(31)(32). To investigate the functional capacity of these putative zR-like cells, we analyzed concentrations of steroids relying on CYP17 activity ( Figure 2F).…”

Regulation of Human 3β-Hydroxysteroid Dehydrogenase Type 2 by Adrenal Corticosteroids and Product-Feedback by Androstenedione in Human Adrenarche

“…Adrenarche is associated with a major expansion of the zona reticularis, which expresses high levels of cytochrome b 5 , leading to selective stimulation of the 17,20-lyase activity of the bifunctional cytochrome P450 c17 to produce DHEA in preference to 17a-hydroxypregnenolone. The zona reticularis also expresses high levels of DHEA-sulfotransferase (SULT2A1) and low levels of both 3bHSD2 mRNA (Rege et al, 2014) and protein (Rainey et al, 2002;Rege and Rainey, 2012). Our inhibition data now suggest that the 3bHSD2 product steroid, androstenedione, may be a key player in limiting the metabolism of DHEA by 3bHSD2 in the zona fasciculata and reticularis during adrenarche.…”

“…A K m /K i ratio of 2.8 shows that androstenedione can decrease DHEA substrate conversion when just a small amount of product steroid has been formed by the enzyme, and explains a primary physiologic mechanism for the decrease in adrenal 3bHSD2 activity in adrenarche. This potent 3bHSD2 inhibition by androstenedione at physiologic intra-adrenal levels (Dickerman et al, 1984) is magnified by the limited expression of 3bHSD2 in the developing zona reticularis (Rege et al, 2014). Cortisone may also competitively inhibit adrenal 3bHSD2, but much higher concentrations compared with androstenedione are required based on the measured K i values.…”