Adrenal Gland Hormones and Divisions

Adrenal Gland Overview

• Adrenal glands are located near the cranial pole of the kidneys.
• They help maintain homeostasis by:
  • Regulating the body's adaptive responses to stress.
  • Maintaining water, sodium, and potassium balance.
  • Controlling blood pressure.
• Main hormones of the adrenal gland belong to two families: steroid hormones (adrenal cortex) and catecholamines (adrenal medulla).

Steroid Hormones (Adrenal Cortex)

• Glucocorticoids (cortisol)
• Mineralocorticoids (aldosterone)
• Androgens (sex hormones)

Catecholamines (Adrenal Medulla)

• Epinephrine
• Norepinephrine

Divisions of the Adrenal Gland

• Microanatomy consists of the cortex and medulla.
• The cortex is mesodermal in origin and has three layers/zones: zona glomerulosa, zona fasciculata, and zona reticularis.
• The medulla is ectodermal in origin.

Adrenal Gland Hormones

• Cortex
  • Zona glomerulosa produces mineralocorticoids.
  • Zona fasciculata produces glucocorticoids.
  • Zona reticularis produces androgens.
• Medulla
  • Adrenal medulla produces catecholamines.

HPA Axis

• Key structures include the hypothalamus, anterior pituitary, and adrenal cortex.
• The hypothalamus releases corticotropin-releasing hormone (CRH).
• The anterior pituitary releases adrenocorticotropic hormone (ACTH).
• The adrenal cortex releases cortisol.

Mechanism of ACTH on Adrenocortical Steroidogenesis

• ACTH acts on the adrenal cortex cells.
• Cholesterol is converted to pregnenolone in the first step.
• This first step is common to all adrenocortical hormones and occurs in the mitochondria.
• ACTH regulates this step (through the adenohypophysis).

Steroid Hormone Synthesis (Steroidogenesis)

• Steroid hormones are derived from cholesterol, which is carried in blood plasma by LDLs.
• Cholesterol enters cells via receptor-mediated endocytosis.
• It is either used immediately or stored in vesicles as cholesterol ester.
• High doses of ketoconazole can reversibly inhibit steroidogenesis, blocking several enzymes in different steps to reduce cortisol levels.

Steroidogenesis in Adrenal Cortex

• Different tissues (zones) of the adrenal gland express different enzymes.
• All processes do not occur in all cells, for example, cells of the zona glomerulosa don't have aromatase.
• Steroid hormones are not stored in vesicles.
• Steroid hormones are secreted immediately by diffusion across the cell membrane when made.

Steroid Hormone Transport

• Hydrophobic steroid hormones are carried in plasma with transport proteins.
• Corticosteroid-binding globulin (CBG) or transcortin are the main transport proteins.
• Albumin also assists in hormone transport.
• Cortisol transport: 75% bound to transcortin, 15% bound to albumin, 10% unbound (free state).
• Aldosterone transport: 10% bound to transcortin, 50% bound to albumin, 40% unbound (free state).

Hormone-Receptor Interaction

• Steroid hormones bind to intracellular receptors, steroid receptor superfamily.
• Steroid receptors can be located in the cytosol or nucleus.
• Cytoplasmic receptors translocate to the nucleus after hormone binding.
• Androgens can bind to cell surface receptors triggering a rapid cellular response.
• Hormones bind to their respective intracellular receptor resulting in a hormone/receptor complex activating transcription of specific genes.

Steroid Hormone Metabolism and Elimination

• Metabolism mainly involves the liver.
• Hormones are modified for excretion.
• Conjugation to sulfates and glucuronides reduces biological potency.
• Hormones become water-soluble for passage in urine.
• The clearance half-life of cortisol is 60 minutes; for aldosterone, it is 20 minutes.

Zona Glomerulosa - Mineralocorticoids

• Mineralocorticoids are corticosteroids that influence salt and water balance.
• Electrolyte and fluid balance is maintained by Na+, K+, and water.
• Aldosterone is the primary mineralocorticoid.

What Stimulates Aldosterone Synthesis and Secretion?

• Hypotension, which is long term regulated by blood pressure (RAAS)
• Increased [K+]

Influence of ACTH on Aldosterone Synthesis

• ACTH has little effect on aldosterone synthesis.
• There are few receptors for ACTH in the cells of zona glomerulosa.

Stimuli for Renin Secretion

• Reduced blood pressure is detected by baroreceptors in the afferent arteriole.
• High potassium (K+) – hyperkalemia occurs.
• Sympathetic stimulation of the juxtaglomerular apparatus via β1 adrenoreceptors acts as a trigger.

Aldosterone Action on Kidney's Distal Tubules

• Aldosterone acts on distal tubules in the kidneys resulting in:
  • Active reabsorption of sodium (Na+).
  • Increased activity of epithelial sodium channels.
  • Synthesis of the sodium-potassium pump (Na+/K+-ATPase).
  • Active secretion of potassium (K+) and protons (H+).
  • Passive reabsorption of water.
• Two steps of the process: lumen (filtrate) → interstitial space → capillary.
• Sodium reabsorption (filtrate to blood) is active.
• Potassium secretion (blood filtrate) is active.
• Process is LED by the Na/K PUMP.