The brown adipose tissue (BAT) is known to regulate whole body energy expenditure through sympathetically activated thermogenesis and therefore protect the body against diet-induced obesity [ 20 ]. Prompted by the altered energy expenditure in metabolic stress condition including HFD and age in SF-1 KO mice, we sought to explore the molecular mechanism regulating energy expenditure by assaying various genes mediating thermogenesis in the BAT. The KO mice showed significantly reduced levels of uncoupling protein 1 (UCP1), beta 3-adrenergic receptor (β3AR), and peroxisome proliferator-activated receptor γ (PPARγ) indicating that SF-1 might be important for the regulation of thermogenesis through activation of BAT especially in metabolic stress condition including high fat diet and aging ( Fig 5A–5C ). It has been suggested that the VMH expresses high level of vesicular glutamate transporter 2 (Vglut2) and the deletion of Vglut2 in SF-1 neurons was reported to induce obesity under high fat diet associated with hyperphagia and blunted response to hypoglycemia [ 14 ]. In the current study, SF-1 deletion in the VMH also induced hyperphagia, hormonal dysregulation and subsequent obesity development. Therefore, we wondered whether deleting SF-1 in the VMH had any effect on Vglut2 expression. Interestingly, we found a marked reduction in Vglut2 expression specifically in the VMH of SF-1 KO mice ( Fig 5D ) suggesting that the obese phenotype and hyperphagia observed in SF-1 KO mice might be, at least in part, linked to the change in Vglut2 expression.

Cells of the zona fasciculata and zona reticularis lack aldosterone synthase (CYP11B2) that converts corticosterone to aldosterone, and thus these tissues produce only the weak mineralocorticoid corticosterone. However, both these zones do contain the CYP17A1 missing in zona glomerulosa and thus produce the major glucocorticoid, cortisol. Zona fasciculata and zona reticularis cells also contain CYP17A1, whose 17,20-lyase activity is responsible for producing the androgens, dehydroepiandosterone (DHEA) and androstenedione. Thus, fasciculata and reticularis cells can make corticosteroids and the adrenal androgens, but not aldosterone.

Biosynthesis of steroid hormones requires a battery of oxidative enzymes located in both mitochondria and endoplasmic reticulum. The rate-limiting step in this process is the transport of free cholesterol from the cytoplasm into mitochondria. Within mitochondria, cholesterol is converted to pregnenolone by an enzyme in the inner membrane called CYP11A1. Pregnenolone itself is not a hormone, but is the immediate precursor for the synthesis of all of the steroid hormones. The following table delineates the enzymes required to synthesize the major classes of steroid hormones.