2-1-16-Steroid Biosynthesis (Theisen) Flashcards
List examples of Glucocorticoids
Cortisol
Cortisone
Corticosterone
All synthesized in adrenal glands –> distributed to large # of tissues and organs –> increases BP and Na uptake in kidneys –> mediates response to stress by increasing protein catabolism and gluconeogenesis and reducing inflammation
List examples of Mineralocorticoids
Aldosterone and 11-deoxycorticosterone
Synthesized in adrenal glands –> distributed to kidney tubules, colon, and parotid gland –> increases Na/H2O retention, K excretion, and BP
List examples of Estrogens
Estradiol and Estrone
Synthesized in ovaries (major), placenta, and adipose tissue –> distributed to primary and secondary repro organs –> mediates feminization, estrous cycle, and inhibits testosterone synthesis
List the types of Lypophilic signaling molecules
Steroid hormones: Progesterone, estradiol, testosterone, cortisol, aldosterone, Vit D (not really a steroid)
Thyroid hormone: Thyroxine
Retinoids: Retinol, retinoic acid
Identify the receptor location and type for Lypophilic signaling molecules
Found in the cytoplasm and nucleus
Family of DNA-binding transcriptional factors
List the general steps in Lipophilic molecule signaling beginning with the signaling molecule (ligand) diffusing across the cell membrane
Lipophilic ligand diffuses across cell membrane –> ligand binds ligand receptor in cytosol –> ligand-receptor complex travels to the nucleus –> Transcription –> Translation –> Cell response
___ hormones regulate cell growth and differentiation into specific cell types, the bodys response to stress, and metabolism of nutrients
Steroid
Steroid receptors are ___ factors
Transcription –> bind to the signaling hormone and to DNA, most of which have a domain that can interact in transcriptional complexes to initiate/repress gene expression
Steroid hormones are synthesized from cholesterol in the ___ of the adrenal cortex, ovaries, and testes. These tissues obtain cholesterol from circulating ___, from de novo synthesis from Acetyl CoA, or from cholesterol esters stored in cytoplasmic lipid droplets
Smooth ER
LDL
The synthesis of steroid hormones begins with the rate-limiting step catalyzed by ____, an enzyme that incorporates a carbonyl group on the D ring of cholesterol and cleaves off a 6-carbon piece of its side chain (between C20 and C22) to form pregnenolone
Desmolase (Catalyzes Cholesterol ——> Prenenolone)
The conversion of cholesterol to prenenolone requires this enzyme ___ and can be stimulated by upregulated levels of ____
Desmolase
ACTH
Aldosterone can be synthesized from progesterone in the ___
Adrenal cortex –> ZONA GLOMERULOSA
Cortisol can be synthesized from progesterone in the _____
Adrenal cortex (zona fasciculata)
Estradiol can be synthesized from progesterone from ___
Testosterone in the ovaries
Minor amt synthesized in adrenal cortex
Testosterone can be synthesized from progesterone in the __
Testes (Dihydrotestosterone is more potent)
Minor amount in adrenal cortex
___ acts as a modulator of neurotransmitter signaling in the brain without being converted to other steroids. It effects the NMDA glutamate receptor (memory and learning)
Pregnenolone (an alcohol)
Pregnenolone must be converted to progesterone for synthesis of other proestrogens via these enzymes:
17-alpha-hydroxylase and 3-beta-hydroxysteroid dehydrogenase
___ is a P-450 family-monooxigenase that is essential for production of pregnenolone.
Desmolase
Desmolase is only found in these tissues:
Tissues that produce steroid hormones –> Gonads and adrenal cortex
Desmolase expression and activity is stimulated by ____
Peptide hormones:
ACTH
LH
FSH
The synthesis of Estrone from Androstenedione is catalyzed by this enzyme ___ and upregulation of ___ in the ovaries
Aromatase
FSH
___ defect leads to salt wasting (hyponatremia) and hypotension due to decreased production of aldosterone and hypoglycemia due to decreased production of cortisol.
In females, this deficiency causes virilism due to increased flow of intermediates into adrenal androgens
21-hydroxylase
A rare deficiency of ___ causes a loss of cortisol as well as sex steroids. However, the decrease in cortisol is compensated for by increased production of corticosterone
17-alpha-hydroxylase
Defects in ___ cause hypertension due to accumulation of 11-deoxycorticosterone, which has mineralocorticoid activity
11-beta-hydroxylase
___ is produced in a tissue-specific manner from progesterone in the adrenal cortex (zona glomerulosa), promotes retention of Na and H2O in kidneys as well as excretion of H and K.
Aldosterone
Reduced levels of aldosterone can lead to ___
Excessive levels of aldosterone can lead to ___
Loss of too much salt
Conn Syndrome-Increased blood volume, hypertension
____ is produced from progesterone in the adrenal cortex (zona fasciculata) and has anti-inflammatory and autoimmune properties. It stimulates the breakdown of muscle, gluconeogenesis, and glycogen synthesis.
Cortisol (glucocorticoid)
Elevated cortisol levels are associated with ___, a condition marked by accumulation of fat on the face and trunk
Cushing Syndrome–> can be caused by increased cortisol production due to pituitary or adrenal tumors or chronic administration of corticosteroids
Glucocorticoids such as cortisol cause immunosuppression by inhibiting both the cell and humoral IR. They induce the production of i-kBa inhibitory protein, which helps sequester the transcription factor ___ in inactive cytoplasmic complexes.
NF-kB
___ is necessary for synthesis of IL-2 (T cell proliferation)
NF-kB
The metabolism of Cortisol —> Cortisone is done through the action of this enzyme:
11-B-hydroxysteroid dehydrogenase
Cortisol has an affinity for ___ receptors and are 100x more concentrated than mineralocorticoids
___ has a much lower affinity for mineralocorticoid receptors
Mineralocorticoid
Cortisone
Natural licorice root contains isoflavones, which are inhibitors of ___
11-beta-hydroxysteroid dehydrogenase
Consumption of real licorice can lead to HTN due to salt retention
The adrogenic potency of testosterone is amplified by its conversion to dihydrotestosterone mediated by the enzyme ____
5-alpha-reductase
___ has a much higher affinity than testosterone for the androgen receptor
DHT
___ is an inhibitor of 5-alpha-reductase which prevents potentiation of testosterone
Finasteride
Used to treat benign prostatic hyperplasia. Has also been used to treat male pattern baldness, which is caused by the action of DHT in the scalp
The effects of Vitamin D are attributed to its active form known as ____
Calcitriol (1,25-dihydroxycholecalciferol)
Technically, not classified as a steroid
___ is the inactive form of Vitamin D and produced in skin from the photochemical cleavage of the B ring of 7-dehydrocholesterol (via UV irradiation in skin)
Cholecalciferol (Vitamin D3)
In the intestine, Cholecalciferol is synthesized from ___
Ergocalciferol (D2)
Once in the liver, Cholecalciferol (D3) is converted to 25-hydroxycholecalciferol by the enzyme ___
25-hydroxylase
In the proximal tubule of the kidneys, 25-hydroxycholecalciferol is converted to 1,25-dihydroxycholecalciferol (calcitriol) by this enzyme ____
1-alpha-hydroxylase
The action of 1-alpha-hydroxylase in conversion of 25-hydroxycholecalciferol to calcitriol in the PCT of the kidneys is stimulated by ___ and inhibited by ___
Stimulates–> PTH, low [PO4]
Inhibits –> Calcitriol
Calitriol stimulates intestinal cells to ____, stimulates reabsorption of ___ in kidneys, and ____ resorption in bone
Ca and PO4 absorption-intestinal cells
Ca-kidneys
Ca-bone
List an example of a Progestin
Progesterone –> synthesized in adrenal glands, ovaries, and testis –> distributed to uterus –> mediates implantation (nidation) and maintenance of pregnancy
___ supports gestation (pregnancy) and embryogenesis and is also involved in the maintenance of the menstrual cycle
Progesterone
A decrease in ___ levels precedes menstruation, labor, and lactation
Progesterone
___ is a glycosylated globulin that belongs to the serine protease inhibitor (SERPIN) family of proteins and is involved in the transport and release of the majority (80-90%) of plasma glucocorticoid hormones and also progesterone
Corticosteroid-Binding Globulin (CBG)
Sex steroids such as testosterone, dihydrotestosterone, and estradiol are transported by the homodimeric glycoprotein ___
Sex steroid hormone binding globulin (SHBG)
Both CBG and SHBG are made mostly in the liver
