Adrenal Glands Physiology PDF

Adrenal gland physiology Mariana Flores MD, MSc [email protected] Objectives List and identify the steps and enzymes involved in the biosynthesis and secretion of adrenal hormones. (STEROIDOGENESIS) Differentiate the physiological actions of mineralocorticoids, glucocorticoids and cathecol...

Adrenal gland physiology Mariana Flores MD, MSc [email protected] Objectives List and identify the steps and enzymes involved in the biosynthesis and secretion of adrenal hormones. (STEROIDOGENESIS) Differentiate the physiological actions of mineralocorticoids, glucocorticoids and cathecolamines. Describe the regulatory mechanisms for mineralocorticoids, glucocorticoids and cathecolamines. Identify the receptors for mineralocorticoids, glucocorticoids and cathecolamines. Introduction Components of the endocrine system. Homeostasis - role in the regulation of: Response to stress Maintenance of body water Sodium & potassium balance Control blood pressure Two different embryologic origins, which influence the mechanisms that control hormone production by each of the two components. Adrenal glands STEROID HORMONES Adrenal cortex: Mineralocorticoids & glucocorticoids (little androgenic hormones) Mineralocorticoids → control electrolytes (Na – K) Glucocorticoids → increase blood glucose concentration. Important protein and fat metabolism MESODERM 90% OF WEIGHT neural crest cells 10% of WEIGHT CATECHOLAMINES >30 steroids: two are exceptional Aldosterone→ mineralocorticoid Cortisol→ glucocorticoid Blood supply Superior, middle, and inferior suprarenal arteries. Blood flows from the outer cortex toward the center area, following a radially oriented sinusoid system. Access of steroid hormones to the circulation and concentrates the steroid hormones at the core of the adrenals. aldosterone synthase Abundant smooth endoplasmic reticulum Mineralocorticoid aldosterone source Regulated by angiotensin II & K Abundant lipid droplets Glucocorticoids, cortisol and corticosterone, and little androgens, DHEA and DHEA sulfate (DHEAS) Regulated mainly by ACTH Develops postnatally and is recognizable at approximately age 3 years Produces glucocorticoids and androgens Regulated mainly by ACTH Adrenal Cortex Adrenal Cortex Regulatory mechanisms Aldosterone and cortisol are regulated by independent mechanisms: Angiotensin II → zona glomerulosa → aldosterone ACTH → zona fasciculata & zona reticularis → cortisol and adrenal androgens Synthesis initial step of steroid hormones are identical in all Acute regulation Rapid production of steroids in response to immediate need Occurs within minutes Ex. glucocorticoids to combat stressful situations & aldosterone to rapidly regulate blood pressure. Chronic stimulation Synthesis of enzymes involved in steroidogenesis to enhance the synthetic capacity of the cells. Ex. Prolonged starvation and chronic disease Adrenal Cortex Regulatory mechanisms Corticotropinreleasing hormone Adrenocorticotropic hormone Hypothalamic-pituitary-adrenal (HPA) axis 80% LDLs Acetate (novo) Coated pits on the adrenocortical cell membranes Steroidogenesis 1. Cholesterol inside the cell 2. Delivered to the mitochondria STeroid Acute Regulatory (STAR) protein Rate-limiting step 3. Cholesterol desmolase →pregnenolone Rate-limiting step ACTH & Angiotensin II → steroidogenesis increase # of LDL receptors & activity of enzymes that liberate cholesterol from LDL. Biosynthesis of adrenal cortex hormones These steps occur in mitochondria and endoplasmic reticulum Each step is catalyzed by a specific enzyme system A change in even a single enzyme causes vastly different types and relative proportions of hormones to be formed. Zona glomerulosa possesses aldosterone synthase activity Zona glomerulosa do not have 17α-hydroxylase activity. Mineralocorticoid Hormone Synthesis Glucocorticoid &Adrenal Androgen Hormone Synthesis Pregnenolone exits the mitochondria and is converted to either progesterone or 17α-OHpregnenolone. Both 17α-OH-pregnenolone and 17α-OH-progesterone can be converted to the androgens DHEA and androstenedione, respectively. DHEA 3β-hydroxysteroid dehydrogenase Glucocorticoid Regulation Corticotropin-releasing hormone (CRH) – Hypotalamus → Adrenocortocotropic Hormone (ACTH) – Anterior pituitary ACTH release is pulsatile aprox: 7–15 episodes per day. The stimulation for cortisol release occurs within 15 minutes of the surge in ACTH. Follows a circadian rhythm Sensitive to environmental and internal factors such as light, sleep, stress, and disease. Release of cortisol is greatest during the early waking hours, with levels declining as the afternoon progresses. Direct stimulation by adrenocorticotropic hormone (ACTH) Cortisol inhibits CRH & ACTH in a negative feedback. ACTH receptor ACTH stimulates cortisol release by binding to a Gαs protein–coupled plasma membrane melanocortin 2 receptor on adrenocortical cells. Glucocorticoids Lipophilic nature Usually found: Conjugated form (eg, as sulfate or glucuronide derivatives) Bound to carrier proteins (noncovalent, reversible binding) Majority of cortisol is bound to glucocorticoid-binding α2-globulin (transcortin or cortisol-binding globulin [CBG]) 20%–50% of bound cortisol is bound nonspecifically to plasma albumin.