Steroid Biosynthesis Lecture (Dr. Theisen) Flashcards

Question

CORTISOL

Answer 1

- A Glucocorticoid - ADRENAL CORTEX (Zona Fasciculata) - Also known ad HYDROCORTISONE - Anti Inflammatory and Autoimmune properties - Stimulates the Breakdown of Muscle. Gluconeogenesis, and Glycogen Synthesis - Elevates leaves associated with CUSHING SYNDROME, a Condition marked by the accumulation of Fat on the Face and Trunk (Can be caused by Increased Cortisol production due to pituitary or Adrenal Tumors or Chronic Administration of Corticosteroids) - Also important Affect on ACTH Feedback Inhibition

Answer 2

- An Estrogen - From TESTOSTERONE in Ovaries - Minor amount in Adrenal Cortex

Answer 3

- An Androgen - And more potent DIHYDROTESTOSTERONE in TESTES - Minor amount in Adrenal Cortex

Answer 4

- Have affinity for Moneralcorticoid Receptors and are 100 times more Concentrated than Mineralocorticoids - Cortisone has MUCH LOWER Affinity for Mineralocorticoids Cortisol ---- (11 Beta Hydroxysteroid Dehydrogenase) ------> Cortisone

Answer 5

- CORTISOL Suppression of the Immune System Glucocorticoids such as CORTISOL cause IMMUNOSUPPRESSION by INHIBITING both Cellular and Humorla Immune Response. - They Induce the production of i-KBa Inhibitory Protein, which helps Sequester the Transcription Factor Nuclear Factor Kappa B (NF-KB) in Inactive Cytoplasmic Complexes. - NF-KB is NECESSARY for the Synthesis of many Cytokines, such as INTERLEUKIN (IL)-2, which are needed for T Cell Proliferation. - Cortisol also promotes T Cell Apoptosis. Decreased IL-2 and its Receptor lead to an INHIBITION of Donal Expression of B Lymphocytes as well.

Answer 6

1) Relatively Common inherited Defect (1 in 12,000 live Births) is in 21 HYDROXYLASE: A) It leads to Salt Washing (Hyponatremia) and Hypotension due to Decreased production of ALDOSTERONE, and Hypoglycemia due to DECREASED PRODCTION OF CORTISOL B) In Females, this Deficiency causes VIRILISM (Development of Male Secondary Characteristics) due to an INCREASED Flow of Intermediates into ADRENAL ANDROGENS 2) A Rare Deficiency of 17 ALPHA HYDROXYLASE - Causes a loss of Cortisol as well as Sex Steroids - However, the Decrease in Cortisol is compensated for by Increased Production of CORTICOSTERONE 3) Defects in 11 BETA HYDROXYLASE - Cause Hypertension due to the accumulation of 11 DEOXYCORTICOSTERONE, which has Mineralocorticoid Activity

Answer 7

- Vitamin D2 (Ergocalciferol) and Vitamin D3 (Cholecalciferol) are found in Liver, Eggs, Fish, Plants, and Vitamin D fortified foods such as Milk and Cereal - Vitamin D3 (Cholecalficerol) is also produced in the Skin via a Mechanism that requires exposure to Sunlight - CALCITROL, the Bioactive form of Vitamin D, is derived from Vitamins D2 and D3

Answer 8

- Progesterone supports Gestation (Pregnancy) and Embryogenesis and is also involved in the maintenance of the Menstrual Cycle. - It regulates the Voltage-Gates Ca2+ Channels on the SPERMATOZOA, prepares the Uterus for IMPLANTATION, causes Smooth Muscle Relaxation, and Decreases Meternal Immune Response. - A Decrease in Progesterone levels precedes Menstruation, Labor, and Lactation

Answer 9

- In normal terms Infants, a Burst of Glucocorticoids during delivery alters the Lung Structure by stimulating the Production of SURFACTANT, which allows the air spaces to Expand. - In preterm Neonates, this process is defective, leading to Infant Respiratory Distress Syndrome (IRDS). - IRDS can be prevented by giving Glucocorticoids to expectant mothers

Answer 10

- The response of Target Tissues to a Steroid Hormone is sometimes determined by further metabolism of the Hormone. For Example, Mineralocorticoid target tissues such as the Kidneys, Colon, and Parotid Gland contain a receptor that has equal affinity for both Mineralo- and Glucocorticoids. - These tissues avoid Na+/ H2O Retention induced by the much higher circulating levels of GLucocoritcoids by metabolizing Cortisol to Cortisone through the action of 11 BETA HYDROXYSTEROID DEHYDROGENASE. - Cortisone has a much lower affinity for the Mineralocorticoid Receptor. - Natural Licorice root contains Isoflavones, which are Inhibitors of 11 BETA DEHYDROGENASE. Therefore, consumption of real Licorice can lead to Hypertension due to Salt Retention - The ANDROGENIC Potency of Testosterone is amplified by its Conversion to DIHYDROTESTOSTERONE (DHT) mediated by the Enzyme 5 ALPHA REDUCTASE. - DHT has a much Higher Affinity than Testosterone for the Androgen Receptor. - FINASTERIDE, an Inhibitor of 5 Alpha Reductase, prevents this potentiation. Finasteride has been used to treat benign Prostatic Hyperplasia. The Drug has also been used to treat MALE PATTERN BALDNESS, which is caused by the action of DHT in the Scalp

Answer 11

- Steroid Hormones are transported in the Blood Complexed to specific Carrier Proteins. The Human Corticosteroid Bidning Globulin (CGB) is a GLYCOSYLATED GLOBULIN that belongs to the Serine Protease Inhibitor (SERPIN) family of Proteins. - CGB is involved in the Transport and Release of the majority (80 to 90%) of Plasma Glucocorticoid Hormones and also Progesterone. - Sex Steroids such as Testosterone, Dihydrotestosterone, and Estradiol are transported by the Homodimeric Glycoprotein, Sex Steroid Hormone Binding Globulin (SHBG), and to a lesser extent by ALBUMIN. - Whereas SHBG is only partially Saturated in Women, its Binding sites are mostly occupied by Testosterone in Men. Both CGB and SHBG are made mostly in the Liver

Answer 12

- The Renin- Angiotensin- Aldosterone System (RAAS) controls Blood Pressure and Fluid Balance. Kidneys release the Enzyme Renin into Circulation when a Low Blood Volume is sensed. - Renin cleaves the Zymogen Angiotensin (Made by the Liver) into Angiotensin I, which is subsequently Proteolytically processed into the Vasoconstrictor Angiotensin II in LUNG Capillaries by Angiotensin- Converting Enzyme (ACE). Angiotensin II stimulates th release of Vasopressin from the Pituitary Gland and the Mineralo-corticosteroid hormone Aldosterone from the Adrenal Cortex. - Aldosterone Blood Pressure and Volume, ACE Inhibitors are widely used in the treatment of Hypertension. Vasopressin acts as a Vasoconstrictor, stimulates Thirst, and Increases Water Retention in the Kidneys

Answer 13

- Glucocorticoids such as Cortisol cause Immunosuppression by Inhibiting both Cellular and Humoral Immune response. They Induce the production of i-KB Alpha Inhibitory Protein, which helps Sequester the Transcription Factor Nuclear Kappa B (NF-KB) in Inactive Cytoplasmic Complexes. - NF-KB is necessary for the Synthesis of many Cytokines, such as Interleukin (IL)- 2, which are needed for T Cell Proliferation. - Cortisol also promotes T Cell Apoptosis. Decreased IL-2 and its receptor lead to an Inhibition of Clonal Expansion of B Lymphocytes as well

Answer 14

- Normal Blood Ca2+ levels are 8.4 to 10.2 mg/dL. Deficiencies in Vitamin D occur due to (1) Inadequate Dietary Intake, (2) Conditions that disrupt the Absorption of Lipids, (3) Poor Functioning of the Liver and Kidneys, (4) Hypoparathyroidism, and (5) Lack of exposure to Sunlight (Ex Winter days in Northern latitudes or excessive use of Sunscreen). - Vitamin D deficiency manifests as BRITTLE BONES observed as RICKETS in Children (marked by Growth Deficiency and Skeletal Deformities), OSTEOMALACIA in adults (Marked by "Pathological Fractures"), and HYPOCALCEMIC TETANY (Involuntary Muscle Contractions due to LOW BLOOD Ca2+). - Intake of too many Vitamin D Supplements causes an Excess of Vitamin D, which results in elevated levels of Ca2+ in Blood (Hypercalcemia) and Urine (Hypercalciuria). - Patients with this condition appear dazed, have a loss of Appetite, and may present with SARCOIDOSIS. The latter is an Inflammatory of Tissues marked by the presence of Clusters of Immune Cells (Granulomas) in various tissues, such as Lungs, Skin, and Lymph Nodes

Answer 15

- Effects of Vitamin D are attributed to its active form (CALCITROL aka 1,15 DIHYDROXYCHOLECALCIFEROL) * **Technically NOT classified as a Steroid - Choelsterol's Sterane is broken during the Synthesis like Steroid Hormones - Though, Vitamin D acts through binding to a Nuclear Receptors and altering the expression of Target genes containing Vitmain D Response Element (VDRE0 sequences VITAMIN D; - Derived from Cholesterol - Has signaling Properties like Steroid Hormones

Answer 16

1) CHOLECALICFEROL (Vitmain D3) is the INACTIVE form of Vitamin D - It is produced in SKIN from the Photochemical Cleavage of the B Ring of 7- DEHYDROCHOLESTYEROL (Via UV IRRADTIATION IN THE SKIN) - In Intestinal Cells from ERGOCALCIFEROL (Vit D3) 2) Subsequent steps for activation take place in the LIVER and the KIDNEYS * **** CHOLECALCIFEROL is FIRST Hydroxylated in the liver by 25- HYDROXYLASE to Generate 25- Hydroxycholecalciferol 3) 25 Hydroxycholecalciferol is then Hydroxylated in the PROXIMAL TUBULES of the Kidneys by: * **1 ALPHA HYDROXYLASE***** - Generates 1,25 DIHYDROXYCHOLECALCIFEROL (Calcitriol) - The action of 1 Alpha HYDROXYLASE is stimulated by PARATHYROID HORMONE (PTH) and Low Blood Concentration of PHOSPHATE but INHIBITED by CALCITRIOL

Answer 17

- Calcitriol stimulates Intestinal Cells to INCREASE the Absorption of Ca2+ and Phosphate from the Intestinal Lumen, INCREASE the Reabsorption of Ca2+ by the Kidneys, and promote RESORPTION of Ca2+ from Bone. - The Resulting effect of CALCITRIOL is and ELEVATION in BLOOD Ca2+ and PHOSPHATE Levels - PTH, Parathyroid Hormone and CALCITONIN are Peptide Signals

Answer 18

- Inadequate Dietary INTAKE - Conditions that Disrupt the ABSORPTION of LIPIDS - Poor Functioning of the Liver and Kidneys - HYPOPARATYROIDISM - Lack of Exposure to SUNLIGHT - BRITTLE BONES and DEFORMITIES A) RICKETTS in Children B) OSTEOMALACIA in Adults = Fractures - HYPOCALCAMIC TETANY (Involuntary Muscle Contractions due to LOW BLOOD CALCIUM)