RNA-Seq Reveals Sub-Zones in Mouse Adrenal Zona Fasciculata and the Sexually Dimorphic Responses to Thyroid Hormone

Abstract

The sex-specific prevalence of adrenal diseases has been known for a long time. However, the reason for the high prevalence of these diseases in females is not completely understood. Mouse studies have shown that the adult adrenal gland is sexually dimorphic at different levels like transcriptome, histology, and cell renewal. Here we used RNA-seq to show that in prepubertal mice, male and female adrenal glands were not only sexually dimorphic but also responded differently to the same external stimulus. We previously reported that thyroid hormone receptor β1 (TRβ1) in the adrenal gland is mainly expressed in the inner cortex and the fate of this TRβ1-expressing cell population can be changed by thyroid hormone (T3) treatment. In the present study, we found that adrenal glands in prepubertal mice were sexually dimorphic at the level of the transcriptome. Under T3 treatment, prepubertal females had 1,162 genes differentially expressed between the saline and T3 groups, whereas in males of the same age, only 512 genes were T3-responsive. Immunostaining demonstrated that several top sexually dimorphic T3-responsive genes, including Cyp2f2 and Dhcr24, were specifically expressed in the adrenal inner cortex, precisely in an area partially overlapping with the X-zone. Under T3 treatment, a unique cortical layer that surrounds the adrenal X-zone expanded significantly, forming a distinct layer peculiar to females. Our findings identified novel marker genes for the inner adrenal cortex, indicating there are different sub-zones in the zona fasciculata. The results also highlight the sex-specific response to thyroid hormone in the mouse adrenal gland.

Early transcriptomic response of mouse adrenal gland and Y-1 cells to dexamethasone

“…These genes were classified as adrenal-expressed genes (14,300 genes). The number of adrenal-expressed genes in the saline-treated group was similar to that in another genome-wide study of adult C57BL/6 mice ( 19 ). The in vivo 1-h Dex-treated group had 862 upregulated genes and 849 downregulated genes ( Fig.…”

Integrative genomic analysis reveals a conserved role for prolactin signalling in the regulation of adrenal function

“… Sexually dimorphic expression of Prlr in the adrenal gland. (A) Overlap of sex‐dependent DEG in mouse ( 4 , 5 , and this study) and rat [ 6 ] adult adrenal gland evidences a core sexually dimorphic expression program. (B) Sexual dimorphic PRLR expression in the human adrenal gland.…”

“…By comparing our list of adrenal sexually dimorphic DEG with data in mouse [ 4 , 5 ] and rat, [ 6 ] we could highlight a core conserved sexually dimorphic gene expression program (Figure 3A and Supporting information Table S11 ). We focused on the role of the PRL receptor (PRLR), because of its conserved sexually dimorphic expression in the human adrenal (Figure 3B ) and the well‐known role of PRL signalling in physiological adaptations and response to stress.…”

Whole Transcriptome Profiling of Adrenocortical Tumors Using Formalin-Fixed Paraffin-Embedded Samples

“…Previous transcriptome studies have shown that APA, CPA, and ACC have distinct gene expression profiles, suggesting that transcriptome profiling can contribute to the accurate diagnosis of adrenocortical tumors (5,6). Furthermore, transcriptome profiling is also a promising technique for elucidating the pathogenesis of adrenal diseases in terms of endocrine function and adrenal differentiation (7,8).…”