Abstract
Adrenal steroid hormone production is a dynamic process stimulated by adrenocorticotropic hormone (ACTH) and angiotensin II (AngII). These ligands initialize a rapid and robust gene expression response required for steroidogenesis. Here, we compare the predominant human immortalized cell line model, H295R cell, with primary cultures of adult adrenocortical cells derived from human kidney donors. We performed temporally resolved RNA-seq on primary cells stimulated with either ACTH or AngII at multiple time points. The magnitude of the expression dynamics elicited by ACTH was greater than AngII in primary cells. This is likely due to the larger population of adrenocortical cells that are responsive to ACTH. The dynamics of stimulus-induced expression in H295R cells are mostly recapitulated in primary cells. However, there are some expression responses in primary cells absent in H295R cells. These data are a resource for the endocrine community and will help researchers determine whether H295R is an appropriate model for the specific aspect of steroidogenesis that they are studying.
Highlights
Steroid hormones signal a coordinated biological response essential to homeostasis.In the adrenal gland, the cortex produces the three major steroid hormone classes, each with distinct roles: the mineralocorticoid aldosterone is the master regulator of blood pressure, the glucocorticoid cortisol is important for the stress response, and androgens determine sex characteristics [1,2]
Steroidogenic expression of primary human adrenocortical (ACTH) or angiotensin II (AngII). (A) Primary cell culture schema: (1) Adrenal gland was coincidentally removed from a cotropic hormone (ACTH)
We focused on characterizing the transcriptome-wide similarities and differences of primary cells stimulated with adrenocorticotropic hormone (ACTH) or AngII
Summary
The cortex produces the three major steroid hormone classes, each with distinct roles: the mineralocorticoid aldosterone is the master regulator of blood pressure, the glucocorticoid cortisol is important for the stress response, and androgens determine sex characteristics [1,2]. The production of these bioactive molecules is highly consequential for human health. Primary aldosteronism is caused by the overproduction of aldosterone and leads to hypertension [3,4,5]. A detailed understanding of the regulation of steroidogenesis is imperative to harness these mechanisms for future treatments
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