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Published on: January 4, 2018
From integrative signalling to metabolic disorders
Mélissa Otis1, Marie-Claude Battista, Mylène Provencher
1Service of Endocrinology, Department of Medicine, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, 3001, 12th Avenue North, Sherbrooke, Quebec, Canada J1H 5N4.
Summary
Cellular environment affects adrenal cortex function. Seladin-1 localization in adrenal cells, influenced by collagen IV, modulates responses to adrenocorticotropin hormone (ACTH) and protects against oxidative stress.
Area of Science:
- Endocrinology
- Cell Biology
- Adrenal Gland Physiology
Background:
- The adrenal cortex exhibits dynamic structural changes crucial for gland function.
- The cellular microenvironment significantly influences adrenal cell functions like proliferation and steroid secretion.
- Specific extracellular matrix proteins modulate cellular responses to hormones.
Purpose of the Study:
- To investigate how extracellular matrix components influence adrenal cell function.
- To elucidate the role of Seladin-1 in modulating adrenocorticotropin hormone (ACTH) responsiveness in adrenal fasciculata cells.
- To understand the dual role of Seladin-1 in steroidogenesis and oxidative stress protection.
Main Methods:
- Cell culture of adrenal glomerulosa and fasciculata cells on different extracellular matrix proteins (fibronectin, collagen IV, laminin).
- Treatment with angiotensin II and ACTH to assess effects on proliferation, protein synthesis, and gene expression.
- Analysis of cytoskeleton-associated proteins and MAPK signaling pathways (p42/44 MAPK, p38 MAPK).
- Assessment of Seladin-1 expression and subcellular localization (cytoplasm vs. nucleus) in response to ACTH in vivo and in vitro.
Main Results:
- Angiotensin II decreased glomerulosa cell proliferation and increased protein synthesis on fibronectin, involving cytoskeleton and MAPK pathways.
- ACTH modulated protein expression and Seladin-1 levels in fasciculata cells cultured on collagen IV, but not fibronectin or laminin.
- ACTH treatment increased Seladin-1 expression and promoted its translocation from cytoplasm to nucleus in rat and human adrenal cells.
- Collagen IV and Seladin-1 together modulate ACTH responsiveness.
Conclusions:
- Extracellular matrix composition dictates cellular responses to hormonal stimuli in the adrenal cortex.
- Seladin-1 plays a dual role: regulating steroidogenesis when cytoplasmic and protecting against ACTH-induced oxidative stress when nuclear.
- Collagen IV is a key factor in mediating ACTH effects on fasciculata cells and Seladin-1 localization.
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