DHCR24, a Key Enzyme of Cholesterol Synthesis, Serves as a Marker Gene of the Mouse Adrenal Gland Inner Cortex

Abstract

Steroid hormones are synthesized through enzymatic reactions using cholesterol as the substrate. In steroidogenic cells, the required cholesterol for steroidogenesis can be obtained from blood circulation or synthesized de novo from acetate. One of the key enzymes that control cholesterol synthesis is 24-dehydrocholesterol reductase (encoded by DHCR24). In humans and rats, DHCR24 is highly expressed in the adrenal gland, especially in the zona fasciculata. We recently reported that DHCR24 was expressed in the mouse adrenal gland’s inner cortex and also found that thyroid hormone treatment significantly upregulated the expression of Dhcr24 in the mouse adrenal gland. In the present study, we showed the cellular expression of DHCR24 in mouse adrenal glands in early postnatal stages. We found that the expression pattern of DHCR24 was similar to the X-zone marker gene 20αHSD in most developmental stages. This finding indicates that most steroidogenic adrenocortical cells in the mouse adrenal gland do not synthesize cholesterol locally. Unlike the 20αHSD-positive X-zone regresses during pregnancy, some DHCR24-positive cells remain present in parous females. Conditional knockout mice showed that the removal of Dhcr24 in steroidogenic cells did not affect the overall development of the adrenal gland or the secretion of corticosterone under acute stress. Whether DHCR24 plays a role in conditions where a continuous high amount of corticosterone production is needed requires further investigation.

Steroidogenesis of Corticosteroids, Genetic Mutation, and Endocrine Disruption Leading to Adrenal Insufficiency

“…It degenerates during puberty in males under the action of androgens. However, in female mice, the X zone reaches its maximum size at around 3 months of age and gradually degenerates with age or rapidly during the first pregnancy under the influence of oestrogens [7,12,13]. The function of the X zone remains unclear, but it is believed to be equivalent to the foetal zone found in human adrenal glands [14].…”

“…In the adrenal cortex cells, cholesterol is present in free form or in esterified form [15]. Cholesterol in adrenal cortex cells is obtained from both dietary intake via several receptors and transporters, including scavenger receptor member B 1 (SCARB1), also called high-density lipoprotein receptor [16,17] and low-density lipoprotein receptor (LDLR), and de novo synthesis within the body [13].…”