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Corticosteroid-binding Globulin (SERPINA6) Establishes Postpubertal Sex Differences in Rat Adrenal Development
Julia N C Toews1, Tristan J Philippe1, Lesley A Hill1
1Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Endocrinology
|September 16, 2022
Summary
Corticosteroid-binding globulin (CBG) is crucial for adrenal development and sex differences in rats. Lacking CBG eliminates these pubertal changes, impacting adrenal growth and gene expression.
Area of Science:
- Endocrinology
- Molecular Biology
- Reproductive Biology
Background:
- Plasma corticosteroid-binding globulin (CBG), encoded by SerpinA6, binds and transports glucocorticoids, regulating cellular access.
- Glucocorticoids and CBG play roles in adrenal development and function, with potential sex-specific influences.
Purpose of the Study:
- To investigate the role of CBG in regulating plasma corticosterone and adrenal development during the pubertal to adult transition in rats.
- To determine if CBG mediates sex differences in adrenal growth, morphology, and gene expression.
Main Methods:
- CRISPR/cas9 gene editing was used to disrupt SerpinA6 gene expression, creating rats lacking CBG.
- Plasma corticosterone, free corticosterone, and adrenocorticotropic hormone levels were measured.
- Adrenal gland weight, zona fasciculata size, and global gene expression were analyzed in wild-type and CBG-deficient rats of both sexes.
Main Results:
- Rats lacking CBG exhibited significantly lower total plasma corticosterone levels (~80% reduction) by adulthood, with a greater absolute decrease in females.
- Adrenal growth and zona fasciculata expansion observed in wild-type females during puberty did not occur in males and were abolished in both sexes lacking CBG.
- Sex differences in adrenal gene expression, including pathways for steroidogenesis and growth, were normalized in CBG-deficient rats, with ~40% of the adrenal transcriptome altered in females lacking CBG.
Conclusions:
- Plasma CBG, produced by the liver, is essential for the pubertal increases in corticosterone and the development of sex differences in adrenal gland growth, morphology, and gene expression in rats.
- CBG's influence on adrenal development is mediated through its regulation of total corticosterone levels, while free corticosterone and ACTH remain comparable.
- These findings highlight a critical role for CBG in mediating sexually dimorphic endocrine and developmental processes during adolescence.
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