Interplay between estrogen-related receptors and steroidogenesis-controlling molecules in adrenals. In vivo and in...

Area of Science:

• Endocrinology
• Molecular Biology
• Cell Biology

Background:

• Estrogen-related receptors (ERRs) α, β, and γ are novel molecules involved in estrogen signaling.
• The specific roles of ERRs in adrenal steroidogenesis and cell morphology are not fully elucidated.

Purpose of the Study:

• To investigate the role of ERRs in regulating adrenocortical cell morphology and steroidogenic function.
• To determine the effects of ERRα antagonism and ERRβ/γ agonism on steroidogenic protein expression and signaling pathways.

Main Methods:

• Pharmacological blockade and activation of ERRs in mouse adrenal tissue and H295R cells using XCT 790 (ERRα antagonist) and DY131 (ERRβ/γ agonist).
• In vivo administration to mice and in vitro exposure of cells to agents.
• Analysis of adrenocortical cell morphology, hormone levels (lutropin, estrogen), cholesterol, and expression of steroidogenic proteins (PLIN, P450scc, TSPO, StAR, HSL, HMGCR).
• Assessment of Ras/Raf, Erk, and Akt signaling pathway activities.

Main Results:

• Both ERRα blockade and ERRβ/γ activation altered adrenocortical cell morphology, lutropin, cholesterol, and estrogen levels.
• ERRα antagonism decreased P450scc, StAR, and TSPO expression.
• ERRβ/γ agonism increased P450scc, StAR, and HMGCR expression, while decreasing HSL expression.
• PLIN expression was upregulated by both treatments.
• Both XCT 790 and DY131 treatments reduced Ras/Raf, Erk, and Akt signaling activities.

Conclusions:

• Estrogen-related receptors play a significant and complex role in maintaining the morpho-functional integrity of adrenocortical cells.
• ERRs exert their effects through specific, opposing, or common regulatory actions on various steroidogenic molecules and signaling pathways.