Adrenal Cortex

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Adrenal Glands: adrenal cortex and medulla

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Cortex zones: -- Zona GLOmerulosa – Aldosterone (mineralcorticoids) -- Zone FASciculata – cortisol and corticosterone (glucocorticoids) -- Zona (S)TETicularis – Androgens and Estradiol (sex steroids)

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Andrenal Hormone synthesis –

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use Cholesterol as the precursor --> uptake of cholesterol is the Rate limiting step in synthesis – L/HDLR - FC - StAR (mito) - CYP 11A1 --> Pregnenolone (prohormone) --- ACTH (corticotropin) helps turn on LDLRec

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Aldosterone (Mineralocorticoids -Na/K) – Zona GLOmerulosa

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Aldosterone – helps maintain blood pressure and volume: 1) Hypotension (Renin-Angiotensin) 2) Hyponatrimia 3) Hyperkalemia (Na/K ratio) ->

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Androgens (testo-DHE) – Zona Reticularis Sex Steroids Male

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Androgens – control aspects of male development and reproductive physiology, bone growth --1) DHEA and 2) Androstenedione

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1) DHEA

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fetal male development --2nd sex chac - drive (little effect) --> Converted to testosterone/estrogen in many tissues – to increase effectiveness

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Use of Anabolic steroids

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Synthetic steroids stimulate same mechanism as endogenous --- Block the actions of glucocorticoids --- Long term abuse leads to liver damage, hypertension, testicular shrinkage and breast growth --- Clinical uses: delayed puberty, muscle loss due to disease, hormone deficits in men

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2) Androstenedione

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(less and weaker effects) – converted to testosterone

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Androgens – Zona Reticularis Sex Steroids Female

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Estradiol – minor compared to reproductive estrogen (follicle), after menopause becomes more important

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Congenital andrenal hyperplasia

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Mutation cause enz deficiencies --- high ACTH (Ant -Pit) no (Aldosterone-Cortisol-Androgen) to neg fb ---> Low Na (Dehydration/ weird HR) -- Puberty early -- large clitoris-penis

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21b-hydroxylase

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no Aldosterone --> salt losing - dehydration/ HR ----- high DHEA --> virilization (masculinization) female wt male sex organ

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11a-hydroxylase

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intermediate mimic aldosteron ---> moderate hypertensive --- high DHEA --> virilization (masculinization) female wt male sex organ

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17 b-hydroxylase

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a lot of Aldosterone ---> EXcessive hypertension ---- no DHEA --> feminizing

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Glucocorticoids -type 1 - lipophilic -

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Transport: corticosteroid-binding globulin (CBG) - transcortin) -- Long half-life -- Binds to intracellular GC receptors to activation (GRE) or repression (HAT) gene expression ----- Conjugated to glucuronic acid (in liver) –> excreted in bile or via kidneys

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Corticol synthesis

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High ACTH (Ant-Pit) --> Pro-opion-melano-cortin (POMC) broken into 3 other hormones --> Melanocyte Sti Horm (MSH-ez to sleep) ---be-lipotropin (break fat to make cortisol - steroid remember) -- be-endorphin (feel good)

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Cortisol Physiological Effects: make sugar (inc glucose plasma)

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Anti-inflam (im-suppress) -- Inc growth adrenal medulla (Epi-Nor: sympa - gluconeogenesis) -- No sex hormone -- Break down muscle - fat - glycogen - more Glucagon

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Cortisol level is high in .....

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day time and stress time (injury-exer-infect-anger-grief-hermorrhage-loose blood)

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Cortisol response stages ---- should NOT last long: Brain can't use Ketone (after Glc gone) -- fat break down and not used --> move to other areas -- Edema

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1) Alarm: Epi-Norepi (Glycogen → glucose, inc BP) ----- 2)
Resistance: Glycogen gone --> Cortisol HIGH (break muscle-fat for glc) --- REduce Immu - inflam -- 3) Exhaustion: Fats gone ---> no more glucocorticoids

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Hypersecretion of cortisol: Cushing’s Syndrome

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Hypotha HIGH - ↑ CRH (F) ---- Adenomas (Ant-Pit cancer) - ↑ ACTH -- Ectopic ACTH (other ACTH cancer: lung) ---- Adenomas (And-Cort) ---- Exogenous use of corticosteroids (over use Prednisone topical)

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Cushing’s SynpTOMs

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Buffalo Torso (fats move to chest) --- Moon face, acne, facial hair (Excess steroids) --- Hypertension (excess Aldosterone) --- Osteoporosis -- Muscular weakness (break for Glc) --- Prone to infection (dec lymphoid) ---
Dark skin (MSH - ACTH secreting tumor) --- Androgenital Syndrome (incr androgens-- enlarged genitals and increased masculinization)

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Diagnosing source of Cortisol: Dexa-methasone --- Treatment

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Use High-dose dexamethosone to suppress ACTH (Ant-Pit) by neg fb ---> if not working --> Adenomas of And Cort (AD cancer) ----- Remove And Cort and HRT (Cortisone- Demamethosone-Prednisone)

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Hyposecretion of cortisol: Addison’s disease

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Autoimm Adrenal Cortex -- Tuberculosis destroys gland -- Cancer --- less ACTH (Ant Pit) --- Enzyme mutations (Inborn errors in metabolism)

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Symptoms of Addison’s disease:

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Hypo-natremia/kalemia/tension (less Aldosteron) -- Fasting hypoglycemia (less cortisol) --- Muscle weakness (no glc no ATP) -- Intolerance to “any stresses” (no beta endorphin, be-lipotropin, MSH, pos fb Epi-Nor, glucagon), ----- Melanin hyperpigmentation mucous membranes and thin skin areas due to excess ACTH (if disease due to adrenal deficit)

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Diagnosis of hyposecretion - Primary (adrenal destruction) versus Secondary (hypo/pit):

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Measure ACTH to determine primary or secondary --- ACTH stimulation test - Addison’s will have no increase in cortisol levels

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Treatment of hyposecretion:

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Immediate or death --- Adrenocorticoid administered daily --- Need to really avoid stress – infection, trauma, ect

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Other uses of Corticosteroid -- Cortisol

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Asthma (inflammation) ----- Poison Ivy (immsuppress) ----- Arthritis (immsupp)