Biochemistry of Steroid Hormones Flashcards
2 Types of Steroid Hormones
Corticoids (made in the adrenal cortex) and sex steroids (made in gonads/placenta)
Classifications of Steroid Hormones
Based on receptors they bind to. Glucocorticoids, mineralocorticoids, androgens, estrogens and progesterone
Glucocorticoids (cortisol) Function
Regulates metabolism, mood, blod pressure, immunity and pain perception
Mineralocorticoids (aldosterone) Function
Electrolyte, maintains blood volume
Androgens (testosterone) Function
Male reproductive developmment
Estrogens Function
Female secondary sexual characteristics and menstural cycle regulation
Progesterones Function
Ovulation regulation, pregnancy maintenance
Adrenal Cortex Synthesises
Mineralocorticoids, Gluococorticoids and androgens
Ovaries Synthesis
Secretes estrogen and progesterone (varying with ovarian cycle)
Testes Synthesis
Produces androgens
What are similar and different between production organs
All have similar pathways but different Enzymes (tissue specififc)
What is a consequence of steroids being lipophilic
Can’t be stored within cells
Adrenal Glands Regulatory Factors
Hypothalamic Hypophysiotropic Hormones and Feedback by Target Gland Hormones
Hypothalamic Hypophysiotropic Hormones
Corticopin Release Hormone (CRH) from hypothalamus stimulates adrenocorothopic Hormone (ACTH) from anterior pituitary, regulating (positive feedback) adrenal hormone production of cortisol.
Target Gland Hormones Outline
Negative feedback through cortisol inhibits hypothalamus and pituitary
Steroids Unique Structure
4 linked hydrocarbon rings, hydrocarbon tail and hydroxyl group. Amphipathic (both hydrophobic and hydrophillic)
Steroid Characteristics
Permeates membrane (hydrophobic portion), travels independently in blood (hydrophilic portion), binds intracellularly (hydrophobic, influence gene expression), they are stored in cell vesticles (are very stable)
Key Steps: Steroid Hormone Synthesis
Hydrocarbon tail shortening, Hydroxylation (adding -OH) of Steroid Nucleus
Hydrocarbon Tail Shortening Outline
Part of tail removed via side chain cleavage
Steroid Nucleus Hydroxylation
Adding OH groups modifies 4 ring structure to produce functional hormones eg Cholesterol
Key Enzymes in Steroid Hormone Synthesis
Cytochrome P450 and StAR
Cytochrome P450(/demolase/CYP11A1) Function, substrates and location
Oxidases molecule. Requires oxygen and NADH. Located in endoplasmic reticulum and adrenal gland, ovary and testes mitochondria
Steroidogenic Acute Regulatory Protein (StAR)
Uptakes cholesterol into mitochondria
What happens to cholesterol in mitochondria
Converted to pregenolone (precursor to all steroid hormones) by cholesterol side chain cleavage. Catalyzed by cytochrome P450
Mineralocorticoids Pathway of Progression
Cholesterol to Pregenoione, Progesterone, deoxycortocosterone, corticosterone and aldosterone
Progesterone Formation
Pregenolone has enzymes converts 3 -OH group to 3 keto (double-bond O) group. Isomerisation changes delta 5 double bond to delta 4
Cortisol Formation
Pogesterone to 17-Hydroxyprogesterone to 11-deoxycortisol to cortisol
Cortisol Function
Metabolism: glucogenesis (increase blood glucose), suppresses inflammation and helps body regulate stress
11-deoxycorticosterone Formation
Hydroxylation (add -OH) at C-21 on progestetrone by 21-alpha-hydroxase
Corticosterone Formation
Hydroxylation of 11-deoxycorticosterone ar C11 by 11-beta-hydroxalase
Aldosterone Formation
Hydroxylation (-OH adding) of C18 on corticosterone and Oxidation (O adding or H removing) of C18 to an aldehyde
Steroid Hormones Cellular Mode of Action Outline
Diffuse across cell membrane (lipophilic), bind to intracellular receptors, Hormone- receptor complex moves to nucleus and binds to HREs on DNA. This binding regulates gene transcription leading to changes in protein synthesis
Alteration of Gene Expression
Alteration to protein synthesis and changes in cellular response.
Aldosterone Function
Increases sodium reabsorption in kidneys, balances salt and water. Increases blood volume and pressure
Testosterone Function
Promotes muscle growths and male characteristics
Estradiol Function
Regulates menstrual cycle and reproductive tissues
Addison’s Disease Outline
Result of glucocorticoid deficiency resulting in insufficient cortisol production. Symptoms: fatigue, low blood pressure, weight loss and skin hyperpigmentation
Hypoaldosteronism Outline
Mineralocorticoid Deficiency results in insufficent alsosterone. Symptoms: Dehydration, hyponatremia (low blood sodium), hyperkalemia (high potassium) and hypotension
Congenital Adrenal Hyperplasia Disorders Outline
Adrenal gland producing insufficient cortisol biosynthesis due to inherited autosomal recessive disorders. Failure to produce cortisol (due to enlarged glands) means loss of negative feed back (no regulation) to HPA axis. Reduced cortisol and aldosterone and androgen overproduction Symptoms vary depending on enzyme(s) effected
