Related Experiment Video
Updated: Aug 19, 2026

Primary Culture of Rat Adrenocortical Cells and Assays of Steroidogenic Functions
Published on: March 12, 2019
ACTH regulates steroidogenic gene expression and cortisol biosynthesis in the human adrenal cortex via sphingolipid
Tuba Ozbay1, Alfred H Merrill, Marion B Sewer
1School of Biology, Parker H. Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, Georgia, USA.
Abstract:
Sphingolipids are a diverse family of phospholipids and glycolipids that mediate cell-cell interactions, participate in signal transduction pathways and modulate the activity of various cellular proteins and receptors. The objective of the present studies was to characterize the role of the sphingolipid biosynthetic pathway in adrenocorticotropin (ACTH)-dependent steroidogenic gene expression and cortisol production. H295R human adrenocortical cells were treated with ACTH or dibutyryl cAMP (Bt2cAMP) for various time periods and the content of sphingolipids was quantified by mass spectrometry. Treatment of H295R cells with ACTH and Bt2cAMP activated sphingolipid metabolism within five minutes. Decreases were found in the cellular levels of several sphingolipids, including sphingomyelin (SM) and glucosylceramide. ACTH/cAMP rapidly decreased levels of the signaling molecules ceramide, sphingosine and sphingosine-1-phosphate (S1P). The effect of these bioactive sphingolipids on steroidogenic gene expression was also examined. Both sphingosine and S1P were found to increase endogenous CYP17 mRNA and activate the transcriptional activity of CYP17-luciferase reporter constructs. Further, sphingosine and S1P rapidly increase cortisol biosynthesis in H295R cells. In summary, our studies establish a link between ACTH/cAMP-dependent steroidogenesis and sphingolipid metabolism in the human adrenal cortex. Finally, these findings suggest that sphingolipids may serve as signaling mediators in ACTH-stimulated cortisol biosynthesis.
Related Concept Videos
Hormones of the Adrenal Glands
The adrenal cortex, a powerhouse of hormone synthesis, generates over two dozen corticosteroid hormones. The zona glomerulosa produces mineralocorticoids, exemplified by aldosterone, influencing the electrolyte composition of body fluids. The synthesis of glucocorticoids such as cortisol and corticosterone...
Cushing Syndrome II: Pathophysiology
Hypothalamic-Pituitary Axis
Cushing Syndrome I: Introduction
Adrenal Gland Disorders
Adrenal insufficiency, characterized by insufficient cortisol and aldosterone production, leads to conditions like Addison's disease. This disorder, affecting the adrenal cortex, exhibits symptoms such as skin bronzing, dehydration, low blood pressure, fatigue, and weight loss. Congenital adrenal hyperplasia, a genetic ailment causing...
Anatomy of the Adrenal Glands
These glands possess a distinctive yellow tinge due to the stored cholesterol and fatty acids required for hormone synthesis. They are encased in a fibrous capsule and cushioned by fat.
The adrenal gland comprises two distinct regions...

