An overview of how<unk>  reductase is driven by NADH production by hexose-6-phosphate and how it affects the HPA Axis in a healthy body.<unk>  effects on HPA and body in presence of deficient H6PD In a healthy body, blood<unk>  and cortisol levels are roughly equimolar.<unk>  leads to an elevated level of inert<unk>  to active cortisol in adipose tissue.<unk>  is caused by dysregulation of the 11β-hydroxysteroid dehydrogenase type 1 enzyme, otherwise known as<unk>  reductase. The 11β-HSD1 enzyme is responsible for catalyzing the interconversion of circulating<unk>  to cortisol, using NADH as a co-factor. The oxidative or reductive capacity of the enzyme is regulated by NADH produced by hexose-6-phosphate dehydrogenase (H6PD). H6PD is distinct from its isozyme, glucose-6-phosphate dehydrogenase (G6PDH) in that G6PDH is a cytolytic enzyme and draws from a separate pool of NAD+. H6PD is also capable of catalyzing the oxidation of several phosphorylated hexoses, while G6PDH shows affinity for glucose, specifically. The enzyme<unk>  reductase exists in a tightly controlled reaction space, facing the lumen of the endoplasmic reticulum of cells in the liver and lungs. NADH produced by hexose-6-phosphate is delivered directly to the catalytic site of<unk>  reductase. If NADH production is limited, then<unk>  reductase is also capable of catalysing the reverse reaction taking circulating cortisol and reducing it to<unk> . Dysregulation of hexose-6-phosphate dehydrogenase occurs as a result of gene mutation. Cortisol is important in signalling inhibition of adrenocorticotropic hormone release from the pituitary. Reduced cortisol in circulation activates the H-P-A Axis to produce and release more cortisol, and therefore androgen. Effect on HPA Axis The Hypothalamic-Pituitary-Adrenal axis relies on blood levels of cortisol to act as negative feedback. Low levels of blood cortisol leads to release of Corticotrope Releasing Hormone (CRH) activating the anterior pituitary and signalling the release of Adrenocorticotropic Hormone (ACTH), stimulating the adrenal gland to make more cortisol. In addition to cortisol, the adrenal gland also releases androgen, leading to hyperandrogenism, which gives rise to the symptoms commonly associated with<unk> .
Cortisone reductase deficiency
Isolated 17,20-lyase deficiency
17β-Hydroxysteroid dehydrogenase III deficiency
5α-Reductase 2 deficiency
Aromatase deficiency
Gonadotropin-releasing hormone insensitivity
Androgen-induced hermaphroditism
Congenital adrenal hyperplasia due to 21-hydroxylase deficiency