From integrative signalling to metabolic disorders.
The adrenal cortex undergoes constant dynamic structural changes, a key element in ensuring integrative functionality of the gland. Studies have shown that the cellular environment can modulate cell functions such as proliferation and steroid secretion. For example, 3-day treatment with angiotensin II promotes protein synthesis with a concomitant decrease in proliferation of glomerulosa cells, when cultured on fibronectin, but not on collagen IV or laminin. These effects involve close interaction between cytoskeleton-associated proteins and activation of p42/p44mapk and p38 MAPK pathways. On the other hand, adrenocorticotropin hormone (ACTH), which is clearly the most potent stimulus of fasciculata cells, induces specific modulation of targeted proteins, when cells are cultured on collagen IV, but not on fibronectin or laminin. In particular, ACTH treatment leads to increased expression of Seladin-1 and induces the relocalization of Seladin-1 from the cytoplasm to the nucleus, both in vivo and in culture conditions, in adult rats and in human fetal adrenal glands. As a whole, these results indicate that Seladin-1, together with collagen IV, is able to modulate ACTH responsiveness. Hence, Seladin-1 may participate in the regulation of steroidogenesis when localized in the cytoplasm, while conversely protecting cells against oxidative stress generated by intense ACTH stimulation when massively localized in the nucleus.
Otis
Mélissa
M
Service 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.
Battista
Marie-Claude
MC
Provencher
Mylène
M
Campbell
Shirley
S
Roberge
Claude
C
Payet
Marcel Daniel
MD
Gallo-Payet
Nicole
N
D000311:Adrenal Glands / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D024141:Collagen Type IV / Q000378:metabolism; D005260:Female; D005353:Fibronectins / Q000494:pharmacology; D006801:Humans; D008659:Metabolic Diseases / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans; D015398:Signal Transduction
D024141:Collagen Type IV; D005353:Fibronectins; D009419:Nerve Tissue Proteins; D000804:Angiotensin II; D000324:Adrenocorticotropic Hormone; C000600134:DHCR24 protein, rat; D044925:Oxidoreductases Acting on CH-CH Group Donors; C499055:DHCR24 protein, human