Zona FasciculataEdit

Zona fasciculata is the middle zone of the adrenal cortex, the outer gland sitting atop the kidneys. Along with the outer zona glomerulosa and the inner zona reticularis, it forms the adrenal cortex, a compactly organized layer dedicated to steroid production. The cells of zona fasciculata are large and lipid-rich, arranged in cords or fascicles, and specialized for making glucocorticoids. The principal glucocorticoid in humans is cortisol, with corticosterone playing a smaller role in some other species. Secretion is tightly controlled by the hypothalamic-pituitary-adrenal axis, with adrenocorticotropic hormone driving the process in response to stress, circadian cues, and metabolic demand. See Adrenal cortex and Adrenal gland for broader context.

Zona fasciculata sits between the outer Zona glomerulosa and the inner Zona reticularis within the adrenal cortex. Its activity is a central component of energy homeostasis and the body’s response to stress. The synthesis of cortisol involves a cascade of steroidogenic enzymes, including 11β-hydroxylase (CYP11B1), which converts 11-deoxycortisol to cortisol. The process relies on the steroidogenic acute regulatory protein (Steroidogenic acute regulatory protein), which moves cholesterol into mitochondria to begin steroid production. The adrenocorticotropic hormone (Adrenocorticotropic hormone) from the Hypothalamus-Pituitary gland axis is the primary regulator, acting through the melanocortin receptor MC2R on zona fasciculata cells to stimulate cortisol synthesis and release via the intracellular cyclic adenosine monophosphate (cAMP) signaling pathway. See CYP11B1, StAR, ACTH, Hypothalamus, and Pituitary gland for related topics.

Structure and development - Anatomy and histology: Zona fasciculata is characterized by hexagonal or polygonal cells with abundant smooth endoplasmic reticulum and lipid droplets, giving a foamy cytoplasmic appearance. The cells are organized into broad fascicles, a histologic hallmark that gives the zone its name. For a broader view of the gland’s architecture, see Adrenal cortex. - Development: The adrenal cortex originates from the mesoderm, with zone specification established during fetal and postnatal life. The distinct borders between zona glomerulosa, zona fasciculata, and zona reticularis reflect region-specific expression of steroidogenic enzymes and regulatory receptors.

Secretion and regulation - Control system: The hypothalamus releases corticotropin-releasing hormone (CRH), which prompts the pituitary to secrete ACTH. ACTH stimulates zona fasciculata to produce cortisol, which feeds back to dampen CRH and ACTH release, creating a negative feedback loop. The entire axis is sometimes described as the Hypothalamic-pituitary-adrenal axis. - Circadian and stress responsiveness: Cortisol levels exhibit a diurnal pattern, peaking in the early morning and dipping at night, with acute elevations in response to stress, illness, and physical exertion. The axis also interacts with other hormonal systems to coordinate energy mobilization and immune responses. See Circadian rhythm and Cortisol for related topics. - Enzymatic pathway: In addition to CYP11B1, steroidogenesis in zona fasciculata involves enzymes that convert precursors through a sequence of steps to cortisol. The precise balance of enzyme activity helps determine cortisol versus other steroid outputs and can vary by species and developmental stage. See 11β-hydroxylase and Steroidogenesis for background.

Physiological roles - Metabolism: Cortisol promotes gluconeogenesis in the liver, mobilizes amino acids from peripheral tissues, and supports glucose availability during fasting or stress. It also influences lipolysis and fat distribution, contributing to energy homeostasis. See Gluconeogenesis and Lipolysis. - Immune and inflammatory response: Cortisol has broad anti-inflammatory and immunosuppressive effects, tempering excessive immune reactions and helping resolve inflammation. Chronic elevation or suppression of cortisol, however, can have adverse consequences for immune function. See Glucocorticoid and Immune system. - Vascular and stress adaptation: By affecting vascular responsiveness and metabolism, cortisol aids the body’s capacity to cope with stressors, coordinating energy supply, tissue repair, and cognitive function. See Circadian rhythm and Gluconeogenesis.

Clinical significance - Disorders of cortisol excess: Hypercortisolism can arise from pituitary sources (e.g., ACTH-secreting adenomas, known in some contexts as Cushing's disease), adrenocortical adenomas or carcinomas producing cortisol, or prolonged exposure to pharmaceutical glucocorticoids. The resulting condition is commonly referred to as Cushing's syndrome. - Disorders of cortisol deficiency: Adrenal insufficiency or impaired ACTH signaling can lead to insufficient cortisol production, a condition known as Addison's disease (often autoimmune in origin). Treatment typically involves careful hormone replacement and management of stress dosing. - Therapeutic use and controversies: Synthetic glucocorticoids derived from cortisol are widely used to treat inflammatory, autoimmune, and allergic conditions, as well as to prevent transplant rejection. While highly effective, long-term use carries risks such as osteoporosis, metabolic syndrome, impaired wound healing, and suppression of the hypothalamic-pituitary-adrenal axis. Clinicians balance therapeutic benefits with potential systemic effects, and research continues on minimizing side effects while preserving efficacy. See Glucocorticoid and Cushing's syndrome for related topics. - Congenital adrenal hyperplasia and related conditions: Deficiencies in enzymes of the steroidogenic pathway (for example, 11β-hydroxylase or 21-hydroxylase) can disrupt cortisol synthesis and shift steroid production toward androgen precursors, yielding a spectrum of developmental and metabolic phenotypes collectively categorized as Congenital adrenal hyperplasia. - Diagnostic considerations: Evaluation of cortisol production and axis activity often involves measuring serum or salivary cortisol, ACTH stimulation tests, and imaging when indicated. See Gluconeogenesis, Cortisol, and ACTH for context.

See also - Adrenal cortex - Adrenal gland - Cortisol - Glucocorticoid - Cushing's syndrome - Addison's disease - Congenital adrenal hyperplasia - ACTH - Hypothalamic-pituitary-adrenal axis - Zona glomerulosa - Zona reticularis - Steroidogenesis - Steroidogenic acute regulatory protein - 11β-hydroxylase