2-1-16-Steroid Biosynthesis (Theisen)

Question 1

List examples of Glucocorticoids

Answer 1

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

Question 2

List examples of Mineralocorticoids

Answer 2

Aldosterone and 11-deoxycorticosterone

Synthesized in adrenal glands –> distributed to kidney tubules, colon, and parotid gland –> increases Na/H2O retention, K excretion, and BP

Question 3

List examples of Estrogens

Answer 3

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

Question 4

List the types of Lypophilic signaling molecules

Answer 4

Steroid hormones: Progesterone, estradiol, testosterone, cortisol, aldosterone, Vit D (not really a steroid)

Thyroid hormone: Thyroxine

Retinoids: Retinol, retinoic acid

Question 5

Identify the receptor location and type for Lypophilic signaling molecules

Answer 5

Found in the cytoplasm and nucleus

Family of DNA-binding transcriptional factors

Question 6

List the general steps in Lipophilic molecule signaling beginning with the signaling molecule (ligand) diffusing across the cell membrane

Answer 6

Lipophilic ligand diffuses across cell membrane –> ligand binds ligand receptor in cytosol –> ligand-receptor complex travels to the nucleus –> Transcription –> Translation –> Cell response

Question 7

___ hormones regulate cell growth and differentiation into specific cell types, the bodys response to stress, and metabolism of nutrients

Answer 7

Steroid

Question 8

Steroid receptors are ___ factors

Answer 8

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

Question 9

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

Answer 9

Smooth ER

LDL

Question 10

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

Answer 10

Desmolase (Catalyzes Cholesterol ——> Prenenolone)

Question 11

The conversion of cholesterol to prenenolone requires this enzyme ___ and can be stimulated by upregulated levels of ____

Answer 11

Desmolase

ACTH

Question 12

Aldosterone can be synthesized from progesterone in the ___

Answer 12

Adrenal cortex –> ZONA GLOMERULOSA

Question 13

Cortisol can be synthesized from progesterone in the _____

Answer 13

Adrenal cortex (zona fasciculata)

Question 14

Estradiol can be synthesized from progesterone from ___

Answer 14

Testosterone in the ovaries

Minor amt synthesized in adrenal cortex

Question 15

Testosterone can be synthesized from progesterone in the __

Answer 15

Testes (Dihydrotestosterone is more potent)

Minor amount in adrenal cortex

Question 16

___ 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)

Answer 16

Pregnenolone (an alcohol)

Question 17

Pregnenolone must be converted to progesterone for synthesis of other proestrogens via these enzymes:

Answer 17

17-alpha-hydroxylase and 3-beta-hydroxysteroid dehydrogenase

Question 18

___ is a P-450 family-monooxigenase that is essential for production of pregnenolone.

Answer 18

Desmolase

Question 19

Desmolase is only found in these tissues:

Answer 19

Tissues that produce steroid hormones –> Gonads and adrenal cortex

Question 20

Desmolase expression and activity is stimulated by ____

Answer 20

Peptide hormones:
ACTH
LH
FSH

Question 21

The synthesis of Estrone from Androstenedione is catalyzed by this enzyme ___ and upregulation of ___ in the ovaries

Answer 21

Aromatase

FSH

Question 22

___ 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

Answer 22

21-hydroxylase

Question 23

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

Answer 23

17-alpha-hydroxylase

Question 24

Defects in ___ cause hypertension due to accumulation of 11-deoxycorticosterone, which has mineralocorticoid activity

Answer 24

11-beta-hydroxylase

Question 25

___ 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.

Answer 25

Aldosterone

Question 26

Reduced levels of aldosterone can lead to ___

Excessive levels of aldosterone can lead to ___

Answer 26

Loss of too much salt

Conn Syndrome-Increased blood volume, hypertension

Question 27

____ 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.

Answer 27

Cortisol (glucocorticoid)

Question 28

Elevated cortisol levels are associated with ___, a condition marked by accumulation of fat on the face and trunk

Answer 28

Cushing Syndrome–> can be caused by increased cortisol production due to pituitary or adrenal tumors or chronic administration of corticosteroids

Question 29

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.

Answer 29

NF-kB

Question 30

___ is necessary for synthesis of IL-2 (T cell proliferation)

Answer 30

NF-kB

Question 31

The metabolism of Cortisol —> Cortisone is done through the action of this enzyme:

Answer 31

11-B-hydroxysteroid dehydrogenase

Question 32

Cortisol has an affinity for ___ receptors and are 100x more concentrated than mineralocorticoids

___ has a much lower affinity for mineralocorticoid receptors

Answer 32

Mineralocorticoid

Cortisone

Question 33

Natural licorice root contains isoflavones, which are inhibitors of ___

Answer 33

11-beta-hydroxysteroid dehydrogenase

Consumption of real licorice can lead to HTN due to salt retention

Question 34

The adrogenic potency of testosterone is amplified by its conversion to dihydrotestosterone mediated by the enzyme ____

Answer 34

5-alpha-reductase

Question 35

___ has a much higher affinity than testosterone for the androgen receptor

Answer 35

DHT

Question 36

___ is an inhibitor of 5-alpha-reductase which prevents potentiation of testosterone

Answer 36

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

Question 37

The effects of Vitamin D are attributed to its active form known as ____

Answer 37

Calcitriol (1,25-dihydroxycholecalciferol)

Technically, not classified as a steroid

Question 38

___ 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)

Answer 38

Cholecalciferol (Vitamin D3)

Question 39

In the intestine, Cholecalciferol is synthesized from ___

Answer 39

Ergocalciferol (D2)

Question 40

Once in the liver, Cholecalciferol (D3) is converted to 25-hydroxycholecalciferol by the enzyme ___

Answer 40

25-hydroxylase

Question 41

In the proximal tubule of the kidneys, 25-hydroxycholecalciferol is converted to 1,25-dihydroxycholecalciferol (calcitriol) by this enzyme ____

Answer 41

1-alpha-hydroxylase

Question 42

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 ___

Answer 42

Stimulates–> PTH, low [PO4]

Inhibits –> Calcitriol

Question 43

Calitriol stimulates intestinal cells to ____, stimulates reabsorption of ___ in kidneys, and ____ resorption in bone

Answer 43

Ca and PO4 absorption-intestinal cells

Ca-kidneys

Ca-bone

Question 44

List an example of a Progestin

Answer 44

Progesterone –> synthesized in adrenal glands, ovaries, and testis –> distributed to uterus –> mediates implantation (nidation) and maintenance of pregnancy

Question 45

___ supports gestation (pregnancy) and embryogenesis and is also involved in the maintenance of the menstrual cycle

Answer 45

Progesterone

Question 46

A decrease in ___ levels precedes menstruation, labor, and lactation

Answer 46

Progesterone

Question 47

___ 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

Answer 47

Corticosteroid-Binding Globulin (CBG)

Question 48

Sex steroids such as testosterone, dihydrotestosterone, and estradiol are transported by the homodimeric glycoprotein ___

Answer 48

Sex steroid hormone binding globulin (SHBG)

Both CBG and SHBG are made mostly in the liver