CHOLESTEROL AND STEROIDS Sterols steroids are class of

CHOLESTEROL AND STEROIDS

• Sterols (steroids) are class of lipids that are derivatives of a tetracyclic hydrocarbon

Steroids • Steroids are lipids containing a steroid nucleus (core structure) • The steroid nucleus is a fused ring system consisting of three cyclohexane rings and one cyclopentane ring • The rings are designated A, B, C and D • Attachment of different groups to the core steroid structure leads to a wide variety of steroid compounds, including cholesterol, bile salts and steroid hormones

Cholesterol • Cholesterol is the most abundant steroid in animals - plants have very small amounts (but have related compounds) - it’s a major component of cell membranes, and affects the fluidity of the membrane due to its bulky structure - is a precursor for biosynthesis of many other steroids • Cholesterol is called a sterol because it contains an alcohol group • We can obtain cholesterol from our diet (animal products), but our liver can also synthesize all the cholesterol that we need - the liver synthesizes more cholesterol when dietary intake is low - excessive blood cholesterol is associated with atherosclerosis and formation of gallstones

History 1855 – Addison’s disease 1856 – Adrenal glands essential for life 1930 – Cortex > medulla 1932 – Cushing’s syndrome 1949 – Hench et al (Steroids in rheumatoid arthritis) 1952 – Aldosterone

Steroid Hormones • Hormones act as chemical messengers • They are important in control of many biological functions • They are secreted from endocrine glands (and placenta) • They react with receptors on cell surfaces to trigger a cascade response • Usually control metabolism at the gene level • Steroid hormones are biosynthesized from cholesterol

Adrenal Corticosteroids • Adrenal corticosteroids are hormones produced in the adrenal glands (located just above the kidneys) • Cortisone (a glucocorticoid) raises the blood glucose level by causing tissues other than the brain to switch to metabolizing fats and proteins; it also suppresses the immune response and can be used as an anti-inflammatory anti-allergy medication • Aldosterone (a mineralcorticoid) regulates ion balance by promoting re-absorbtion of Na+, Cl- and HCO 3 - by the kidneys • Prednisone is a synthetic corticoid used to treat various inflammatory conditions, such as asthma and rheumatoid arthritis

CHOLESTEROL IS THE BIOSYNTHETIC SOURCE OF ALL STEROID HORMONES • Five major classes of hormones – Progestins (regulate events during pregnancy and are precursors to all other steroid hormones) – Androgens (male sexual characteristic development and maintenance) – Estrogens (female sexual characteristics development and maintenance) – Glucocorticoids (promote gluconeogenesis, and in certain doses suppress inflammation rxns) – Mineralocorticoids (regulate ion balance in kidney)

Glucocorticoids (e. g. , prednisolone) used to suppress inflammation, allergy and immune responses. Anti-inflammatory therapy is used in many illnesses (e. g. , Rheumatoid Arthritis, Ulcerative Colitis, Bronchial Asthma, eye and skin inflammations).

Triamcinolone: used for severe asthma and for local joint inflammation (intra-articular inj. ).

Beclometasone, diproprionate, budesonide: used in asthma, (aerosol).

BILE ACIDS ARE CHOLESTEROL DERIVATIVES • Emulsify dietary lipids • Secreted from liver, stored in gall bladder, passed through bile duct into intestine • Bile acids represent a major metabolic fate of cholesterol, accounting for more than half of the 800 mg/day of cholesterol metabolized (steroid hormones represent about 50 mg of cholesterol per day) • Bile acids are recycled through small intestine

Bile Salts • Bile salts are synthesized from cholesterol in the liver - they are stored in the gall bladder and released into the upper small intestine to help break down fats and oils (like soaps) - too much accumulated cholesterol in the gall bladder can lead to gallstones; if a gallstone passes into the bile duct, severe pain results and the gallbladder often has to be removed

FATE OF CHOLESTEROL • Cholesterol is used by cells to decrease fluidity of cell membrane • Used in steroid hormone biosynthesis • Used in Vit A D E K biosynthesis • Cholesterol can also be exported from liver as bile acids, cholesteryl esters, or biliary cholesterol – Cholesteryl esters are transported to other tissues to use cholesterol

Androgens • - male sex hormones – synthesized in the testes – responsible for the development of male secondary sex characteristics

Negative Health Effects Acne Irritability and aggression (ROID RAGE) Elevated cholesterol levels Adolescent use may cause a premature stop in lengthening bones (Stunted growth) • Mood swings (extremes) • •

Negative Effects, cont. • Injecting users subject themselves to Hepatitis or HIV. • Withdrawal symptoms when one stops using steroids: mood swings, fatigue, restlessness, loss of appetite, insomnia, reduced sex drive, and depression. • Depression can lead to suicide. • If untreated, the withdrawal symptoms could last up to a year after stopping the use.