Steroid Biosynthesis (Staudinger) Flashcards

Question

What are the 2 ways cholecalciferol (vitamin D3) is obtained?

Answer 1

1) **through diet**: ergocalciferol (vit D2) is absorbed in **intestine** from dietary sources 2) converted from **7-dehydrocholesterol** in the **skin** via UV radiation: 7-dehydrocholesterol is an intermediate of cholesterol found at high levels in the skin

Answer 2

- **absorbed** in the skin and intestines - **liver**: cholecalciferol (vit D3) \> (**25-hydroxylase**, liver specific enzyme) \> **25-hydroxycholecalciferol** (found exclusively in the liver) - **kidneys**: 25-hydroxycholecalciferol \> (**1-α-hydroxylase**, (+) by PTH, low phosphate; (-) by calcitriol) \> **1,25-dihydroxycholecalciferol**

Answer 3

- whether ingested or cutaneously synthesized, vit D is initially inert in the form of D2 or D3 - D3 is converted to its protein-bound circulating form in the **liver** \> **25-hydroxy vitamin D** - **25-hydroxy vitamin D**: transported to **kidney**, where under direction of circulating PTH, is converted by **1-α-hydroxylase** to its **active** form **1,25-dihydroxy** vitamin D (**calcitriol**)

Answer 4

- progesterone supports gestation and embryogenesis and is known to involved in maintenance of menstrual cycle - regulates the voltage gated Ca2+ channels on the spermatozoa, prepares the uterus for implantation, causes smooth muscle relaxation, and decreases maternal immune response - decrease in progesterone levels precedes menstruation, labor, and lactation

Answer 5

- in normal term infants, a burst of glucocorticoids preceding delivery alters the lung structure by stimulating the production of surfactant (mainly DMPC) which allows air spaces to expand - in preterm neonates, this process is defective, leading to infant respiratory distress sydrome (IRDS) - IRDS prevented by giving glucocorticoids to expectant mothers

Answer 6

- response of target tissue to a steroid hormone is sometimes determined by further metabolism of the hormone - example: mineralcorticoid target tissues (kidneys, colon, parotid gland) contain a receptor that has equal affinity for both mineralo- and glucocorticoids; these tissues avoid Na+/H2O retention induced by much higher circ levels of glucocorticoids by metabolizing cortisol to cortisone through action of 11 β-hydroxysteroid dehydrogenase; cortisone has much lower affinity for the mineralocorticoid receptor; natural licorice root contains isoflavones which are inhibitors of 11 β-hydrogenase, therefore consumption of real licorice can lead to hypertension due to salt retention - example: testosterone is amplified by its conversion to DHT mediated by the enzyme 5α-reductase; DHT has much higher affinity than testosterone for the androgen receptor; Finasteride, an inhibitor of 5α-reductase, prevents this potentiation and has been used to treat benign prostatic hyperplasia and male pattern baldness (caused by DHT in the scalp)

Answer 7

- steroid hormones are transported in the blood complexed to specific carrier proteins - human **corticosteroid-binding globulin (CBG)** is a glycosylated globulin that belongs to the serine protease inhibitor (SERPIN) family of proteins - CBG is involved in the transport and release of majority (80-90%) of plasma glucocorticoid hormones and progesterone - sex steroids are transported by homodimeric glycoprotein, **sex steroid hormone binding globulin (SHBG)**, and to a lesser extend by albumin - SHBG is only partially saturated in women, its binding sites are mostly occupied by testosterone in men - both CBG and SHBG are made mostly in the liver

Answer 8

- RAAS controls BP and fluid balance - kidneys release renin (enzyme) into circulation when low blood volume is sensed - renin cleaves zymogen angiotensin (made by liver) into angiotensin I, which is proteolytically processed into vasocontrictor angiotensin II in lung capillaries by angiotensin-converting enzyme (ACE) - angiotensin II stimulates release of vasopressin from pituitary gland and mineralocorticoid hormone aldosterone from the adrenal cortex - aldosterone acts of kidneys to increase Na+ and water absorption, raising BP and volume - ACE inhibitors are widely used in tx for HTN - vasopressin acts as vasocontrictor to stimulate thirst and increase water retention in kidneys

Answer 9

- causes immunosuppression by inhibiting both cellular and humoral immune responses - induces prod of i-κBα inhibitory protein, which helps sequester the transcription factor nuclear factor kappa B (NF-κB) in inactive cytoplasmic complexes - NF-κB is necessary for synthesis of many cytokines, such as IL-2, which are needed for T cell proliferation - cortisol also promotes T cell apoptosis - decreased IL-2 and its receptor can lead to inhibition of clonal expansion of B cells as well

Answer 10

(nml blood Ca2+ levels 8.4-10.2 mg/dL) - deficiencies occur due to: 1) inadequate diet intake 2) conditions that disrupt absorption of lipids 3) poor functioning of liver and kidneys 4) hypoparathyroidism 5) lack of sun exposure - deficiency manifests as brittle bones observed in rickets in children (growth deficiency, skeletal deformities), osteomalacia in adults (pathological fractures), and hypocalcemic tetany (involuntary muscle contractions due to low blood Ca2+) - intake of too many vit D supps causes excess, which results in elevated Ca2+ in blood (hypercalcemia) and urine (hypercalciuria); patients will appear dazed, loss of appetite, and may present w/ sarcoidosis (inflammation of tissues marked by presence of clusters of immune cells (granulomas) in various tissues such as lungs, skin, and nodes)