Abstract
Corticosteroid-binding globulin (CBG) is synthesized by the liver and secreted into the bloodstream where binds to glucocorticoids. Thus CBG has the role of glucocorticoid transport and free hormone control. In addition, CBG has been detected in some extrahepatic tissues without a known role. CBG-deficient mice show decreased total corticosterone levels with missing of classical sexual dimorphism, increased free corticosterone, higher adrenal gland size and altered HPA axis response to stress. Our aim was to ascertain whether CBG deficiency could affect the endocrine synthetic activity of adrenal gland and if the adrenal gland produces CBG. We determined the expression in adrenal gland of proteins involved in the cholesterol uptake and its transport to mitochondria and the main enzymes involved in the corticosterone, aldosterone and catecholamine synthesis. The results showed that CBG is synthesized in the adrenal gland. CBG-deficiency reduced the expression of ACTH receptor, SRB1 and the main genes involved in the adrenal hormones synthesis, stronger in females resulting in the loss of sexual dimorphism in corticosteroid adrenal synthesis, despite corticosterone content in adrenal glands from CBG-deficient females was similar to wildtype ones. In conclusion, these results point to an unexplored and relevant role of CBG in the adrenal gland functionality related to corticosterone production and release.
Highlights
Glucocorticoids are steroid hormones secreted by the adrenal gland that perform pleiotropic functions
We investigated in adrenal glands from WT and Corticosteroid-binding globulin (CBG)-deficient (KO) mice the expression of: the ACTH receptor (MC2R), the proteins involved in cholesterol uptake, and its transport to mitochondria where steroidogenesis takes place and the main enzymes involved in corticosterone, aldosterone and catecholamine synthesis
The results showed that CBG is present in the adrenal gland and its absence elicits a female-specific reduced expression of the main proteins involved in the adrenal hormone production resulting in the loss of the adrenal sexual dimorphism
Summary
Glucocorticoids are steroid hormones secreted by the adrenal gland that perform pleiotropic functions. The present study aimed to ascertain whether CBG deficiency affects the synthetic endocrine activity of adrenal gland in male and female mice. For this purpose, we investigated in adrenal glands from WT and CBG-deficient (KO) mice the expression of: the ACTH receptor (MC2R), the proteins involved in cholesterol uptake (scavenger receptor class B member 1, SRB1), and its transport to mitochondria where steroidogenesis takes place (steroidogenic acute regulatory protein, StAR) and the main enzymes involved in corticosterone, aldosterone and catecholamine synthesis. The results showed that CBG is present in the adrenal gland and its absence elicits a female-specific reduced expression of the main proteins involved in the adrenal hormone production resulting in the loss of the adrenal sexual dimorphism
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