SOCS3 expression in SF1 cells regulates adrenal differentiation and exercise performance

Area of Science:

• Endocrinology
• Exercise Physiology
• Molecular Biology

Background:

• Cytokine signaling is integral to exercise adaptations.
• Steroidogenic factor-1 (SF1) cells are key in endocrine functions.
• SOCS3 (Suppressor of Cytokine Signaling 3) modulates cytokine signaling.

Purpose of the Study:

• To investigate the role of cytokine signaling via SOCS3 in SF1 cells during resistance exercise.
• To determine the impact of SF1 cell-specific SOCS3 deficiency on training adaptations and metabolic responses.

Main Methods:

• Generated SF1 Socs3 knockout (KO) mice lacking SOCS3 specifically in SF1 cells.
• Assessed adrenal gland histology, basal hormone levels (ACTH, corticosterone), and ACTH-induced corticosterone secretion.
• Evaluated metabolic parameters (adiposity, glucose tolerance, energy expenditure) and exercise performance (vertical ladder climbing) before and after resistance training.
• Measured counter-regulatory responses to 2-deoxy-d-glucose.

Main Results:

• SF1 Socs3 KO mice displayed persistent fetal adrenal zone markers and altered lipid droplet distribution.
• These mice showed blunted ACTH-induced corticosterone secretion but maintained basal levels.
• Overall metabolic responses to training were unaffected, yet training performance and glucose control during exercise were impaired.
• A reduced counter-regulatory response to 2-deoxy-d-glucose was observed in SF1 Socs3 KO mice.

Conclusions:

• SOCS3 in SF1 cells plays a novel role in adrenal gland differentiation and terminal differentiation.
• Cytokine signaling in SF1 cells is essential for sustaining training performance, likely by facilitating metabolic adjustments during exercise.
• This highlights a critical link between endocrine function and exercise physiology mediated by SOCS3.