Mohammed N Sabir nov 2019 Steroids 11152019 2 Lecture overview Bile acids Indigenous steroids biological functions 11152019 3 Bile acids Formed from cholesterol in liver and stored in Gall Bladder ID: 765237
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Mohammed N. Sabir nov. 2019 Steroids
11/15/20192Lecture overviewBile acidsIndigenous steroids, biological functions
11/15/20193Bile acids…
Formed from cholesterol in liver and stored in Gall Bladder. 15 تشرين الثاني، 19 4
15 تشرين الثاني، 195www.mydr.com
Enterohepatic Circulation 15 تشرين الثاني، 19 6 Cholic acid Deoxycholic acid Intestinal microflora
Enterohepatic Circulation 15 تشرين الثاني، 19 7 Chenodeocycholic acid Lithocholic acid Intestinal microflora
Presence of Deoxycholic acid and Chenodeoxycholic acid in bile is attributed to enterohepatic circulation.15 تشرين الثاني، 19 8
Bile acids do not exist in free form, but rather in conjugation with Glycine and Taurine15 تشرين الثاني، 19 9
They act as emulsifying agents to aid in the intestinal absorption of fat. 15 تشرين الثاني، 1910
15 تشرين الثاني، 1911Types of gallstones:-Non-calcified gall (cholesterol) stones.Black pigment “Calcified gallstones”.Mixed Brown pigment.
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15 تشرين الثاني، 1913medicinembbs.blogspot.com www.studyblue.com Cholesterol gallstones
15 تشرين الثاني، 1914Black pigmentreference.medscape.com www.flickr.com
15 تشرين الثاني، 1915Symptoms of non-silent gallstone:-Pain in the upper abdomen and upper back; the pain may last for several hours.Nausea.Vomiting. Other gastrointestinal problems, including bloating, indigestion, heartburn and flatulence.
15 تشرين الثاني، 1916Causes of Gallstones:-GeneticsObesityDecreased motility (movement) of the gallbladder Diet
15 تشرين الثاني، 1917Risk Factors for Gallstones include:-Genetics.Obesity. Increase cholesterol levelEstrogen. Estrogen can increase cholesterol and reduce gallbladder motility. Ethnic background . Native Americans and Mexican-Americans.
15 تشرين الثاني، 1918Risk Factors for Gallstones include:-Gender and age. Gallstones are more common among women and older people.Cholesterol drugs. Cholesterol-lowering drugs increase the amount of cholesterol in bile.
15 تشرين الثاني، 1919Risk Factors for Gallstones include:-Diabetes. People with diabetes tend to have higher levels of triglycerides which is a risk factor for gallstones.Rapid weight loss. If a person loses weight too quickly and fasting, his or her liver secretes extra cholesterol.
15 تشرين الثاني، 1920Treatment of gallstones:-CholecystectomyOral Dissolution Therapy.Extracorporeal Shock Wave Lithotripsy (ESWL)
Chenodeoxycholic acid and Ursodeoxycholic acid are used as Cholelithiolytic agents.15 تشرين الثاني، 1921 Oral Dissolution Therapy…
Chenodiol (Chenodeoxycholic acid)Suppresses hepatic synthesis of cholesterol and cholic acid, contributing to biliary cholesterol desaturation and gradual dissolution of radiolucent cholesterol gallstones.15 تشرين الثاني، 1922
Chenodiol (Chenodeoxycholic acid)Has no effect on radiopaque (calcified) gallstones or on bile pigment gallstones.15 تشرين الثاني، 1923
-The duration of the treatment lasts for about 2 years or more. -Recurrent of 50% gallstones may recur after discontinuation of therapy.15 تشرين الثاني، 1924
Side effects:-Hepatic damage, manifested by elevated liver enzyme markers.Diarrhea.Dose related hepatotoxicity.15 تشرين الثاني، 1925
Ursodiol (ursodeoxycholic acid)Decreases the formation of lithocholic acid.15 تشرين الثاني، 1926
Ursodeoxycholic acid are used in chronic liver diseases such as “Primary Biliary Cirrhosis” which is an Autoimmune Disease.15 تشرين الثاني، 1927
Rowachol ®Contains essential oils that dissolve cholesterol gallstones through decreasing cholesterol content on bile.15 تشرين الثاني، 1928
It also increases bile production and relaxes bile duct smooth muscles.15 تشرين الثاني، 1929 Pinene ( α + β ) 17 mg Camphene 5mg Cineol 2mg L-Menthol 32mg Menthone 6mg Borneol 5mg
11/15/201930The significance of steroids in human health…Cellular integrityCellular signal transductionIndigenous hormonesLipid profileBlood homeostasis Blood pressure Immune system Growth Are their other significances?
11/15/201931Cholesterol and cellular integrity…
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11/15/201934Signal transduction…
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11/15/201938Blood homeostasis, blood pressure and hyperlipidemia…
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11/15/201940Atherosclerosis
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11/15/201942Indigenous hormones…
11/15/201943Regulation of gene expression by steroid hormones
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11/15/201945Some steroids act as hormones; hence they are called steroid hormones ex.:
11/15/201946Vitamin-D is also considered as a steroidal hormone…
11/15/201947The classification of steroid hormones is according to the receptors which they interact, and these are;glucocorticoids, mineralocorticoids, androgens, estrogens , and progestins
11/15/201948Cortisol: A glucocorticoid synthesized from progesterone in the zona fasciculata of the adrenal cortex. Involved in stress adaptation, elevation of blood pressure and Na+-uptake and affects the immune system
11/15/201949Aldosterone: A mineralocorticoid, produced from progesterone in the zona glomerulosa of adrenal cortex. Elevates blood pressure through increasing Na + -uptake and fluid volume.
11/15/201950Testosterone: An androgen, male sex hormone synthesized in the testes.It is responsible for secondary male sex characteristics and functions.
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11/15/201952Estradiol: An estrogen, principal female sex hormone, produced in the ovary.Responsible for secondary female sex characteristics and functions.
11/15/201953Progesterone: It is produced directly from pregnenolone and secreted from the corpus luteum . Responsible for changes associated with luteal phase of the menstrual cycle. It is also involved in the differentiation of mammary glands
11/15/201954The natural steroid hormones are lipids and they are synthesized from cholesterol in the gonads and adrenal glands.
11/15/201955Adrenal hormonesGLUCOCORTICOIDS AND MINERALOCORTICOIDS
11/15/201956Gonadal hormones
11/15/201957Synthetic steroid hormonesGlucocorticoids: prednisone, methylprednisolone, dexamethasone, triamcinolone, budesonide. Mineralocorticoid: fludrocortisoneAndrogens: oxandrolone , nandrolone (also known as anabolic steroids) Estrogens: diethylstilbestrol (DES) Progestins : norethindrone , medroxyprogesterone acetate
11/15/201958Analysis of the steroid hormone receptors had reliedlargely on biochemical techniques.It is only after the genes encoding these receptors were cloned, it became possible to carry out detailed studies on the various functional domains of receptors.
11/15/201959Cellular localization of steroid hormones receptors showed that these receptors are localized in the nucleus.These findings was confirmed by immunochemical studies which also revealed that these receptors are nuclear receptors.
11/15/201960Cloning of steroid hormone receptorsNature. 1985 Dec 19-1986 Jan 1;318(6047):635-41.Primary structure and expression of a functional human glucocorticoid receptor cDNA.Hollenberg SM, Weinberger C, Ong ES, Cerelli G, Oro A, Lebo R, Thompson EB, Rosenfeld MG, Evans RM. Identification of complementary DNAs encoding the human glucocorticoid receptor predicted two protein forms, of 777 (alpha) and 742 (beta) amino acids, which differ at their carboxy termini. The proteins contain a cysteine/lysine/arginine-rich region which may define the DNA binding domain.
11/15/201961Comparison of the deduced amino acid sequences encoded by many of the receptor cDNAs showed that they were members of a ligand-activated superfamily of transcription factors.
11/15/201962Type I receptorsType II receptorsThey undergo nuclear translocationupon ligand activation and bind ashomodimers to inverted repeat DNA half sites, called hormone response elements, or HREs. Ex. Receptors activated by steroid ligands, such as glucocorticoid receptor, Mineralocorticoid receptor, estrogen receptor, progesterone receptor and androgen receptor. These are often retained in the target cell nucleus regardless of the presence of ligand, and usually bind as heterodimers with RXR to direct repeats. Ex. Receptors for thyroid hormone, all trans retinoic acid and vitamin D
11/15/201963Steroid Receptors bind to Hormone Response Elements (HREs) on DNA, HRE target gene 5’ flanking regionFollowing hormone binding, intracellular receptors act as transcription factors, binding to hormone response elements (HREs) on the 5’ flanking region of target genes. HRE Target gene 5’ flanking region
11/15/201964Steroid Receptors bind to Hormone Response Elements (HREs) on DNAHormoneConsensus HREs Progesterone, Androgen, Glucocorticoid, Mineralocorticoid AGAACAnnnTGTTCT Estrogen AGGTCAnnnTGACCT
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11/15/201969Cholesterol biosynthesis inhibitors…Adverse reactions…MyopathyLiver injuryDiabetes mellitusNeuropathy Amnesia Pancreatic and liver dysfunction Sexual dysfunction Rhabdomyolysis
11/15/201970Cholesterol biosynthesis inhibitors…Drug interactions…GrapefruitBitter orangesCYP450 inhibitors or enhancers
11/15/201971Thank You for listeningAny questions?