Lecture 10: Biosynthesis of Steroid Hormones

Question 1

modes of cell-cell communication

Answer 1

-juxtacrine signaling
-endocrine signaling
-paracrine signaling
-synaptic/neuronal signaling
-autocrine signaling

Question 2

Juxtacrine signaling

Answer 2

-direct physical contact

Question 3

Endocrine signaling

Answer 3

-travels far through blood to target organ
-low concentration
-high affinity receptors
-minutes to hours

Question 4

Paracrine signaling

Answer 4

-travels short distance
-affects neighboring cells
-rapid and localized communication

Question 5

synaptic/neuronal signaling

Answer 5

-neurotransmitter
-short distance
-high local concentration
-dissociate rapidly
-millisecond termination

Question 6

autocrine signaling

Answer 6

-made and functions in same cell

Question 7

Steroid hormone structure

Answer 7

-made from cholesterol
-planar, rigid, hydrophobic
-tight binding to receptors
-low concentrations in body
-bound to serum carrier proteins

Question 8

Steroid hormone action

Answer 8

-diffuse through cell membrane
-bind steroid hormone receptor
-regulate transcription of a specific set of genes

Question 9

Classes of steroid hormones

Answer 9

-sex and progestational hormones
-adrenocortical hormones

Question 10

sex and progestational hormones

Answer 10

-progesterone
-17B-estradiol
-testosterone

Question 11

Adrenocortical hormones

Answer 11

-Cortisol
-Aldosterone

Question 12

structure of steroid hormones

Answer 12

-share 4 rings of cholesterol

Question 13

Steroid receptors

Answer 13

-intracellular
-bind steroid hormones
-regulate transcription of specific set of genes
-belong to nuclear family

Question 14

Steroid receptor structure

Answer 14

-DNA-binding domain
-hormone-binding domain

Question 15

Hormone Responsive Elements (HRE)

Answer 15

-specific DNA seq
-binds to active, dimerized steroid receptors
-binds DNA-binding domain
-alters rate of transcription

Question 16

negative feedback loop?

Answer 16

slide 15?

Question 17

Synthesis of steroid hormones

Answer 17

-Cholesterol to pregnenolone
-P450

Question 18

Pregnenolone to Aldosterone

Answer 18

-Pregnenolone to progeterone
-progesterone to aldosterone (ADRENAL)

Question 19

Pregnenolone to DHEA

Answer 19

-17a-hydroxylase (adds -OH)
-17,20-Lyase (=O)

Question 20

I’m not writing all those down

Answer 20

SLide 17 like actually

Question 21

17a-hydroxylase deficiency

Answer 21

-rare form of congenital adrenal hyperplasia
-mutations in CYP17A1
-overproduction of mineralcoricoids
-deficiency of corticosteroids and sex hormones

Question 22

17a-hydroxylase symptoms

Answer 22

-HYPOcortisolism (enlargement of adrenal glands)
-ambiguous genitalia
-hyperaldosteronism (HTN)

Question 23

21-hydroxylase

Answer 23

-adds -OH to methyl on progesterone

Question 24

21-hydroxylase deficiency

Answer 24

-major form of congenital adrenal hyperplasia
-mutations in CYP21A2

Question 25

21-hydroxylase deficiency symptoms

Answer 25

-hypocorisolism -hypoaldosteronism (hyponatremia can be life threating in infants)

Question 26

21-hydroxylase deficiency premature androgen exposure

Answer 26

-ambiguous genitalia in female -hirsutism -early epiphyseal closure = short height

Question 27

Synthesis of testosrerone and estradiol location

Answer 27

-ovaries and testes -androstenedione too testosterone -testosterone to 17B-estradiol -17,20-Lyase

Question 28

Transport of steroids

Answer 28

-by plasma proteins in plasma -corticod-binding globulin (transcortin) -sex hormone binding globuling (SHBG)

Question 29

corticoid-binding globulin (transcortin)

Answer 29

-transport glucocorticoids and progesterone

Question 30

sex hormone binding globulin (SHBG)

Answer 30

-transport testosterone and estradiol

Question 31

Steroid metabolism

Answer 31

-in liver -oxidation, sulfation, gglucoronidation to soluble forms

Question 32

Steroid excretion

Answer 32

-in bile (estrogen) -in urine (progesterone, androgen, glucocorticoids)

Question 33

Aminoglutethimide

Answer 33

-inhibits aromatase and P450scc -used to block steroid production in some hormone-dependent tumors (breat/prostate)

Question 34

Ketoconazole

Answer 34

-antifungal at lower concentrations (block ergosterol synthesis) -inhibits P450scc, 17a-hydroxylase, and 11B-hydroxylase -can treat hyperglucocorticoid states (cushing's syndrome) -may cause toxic side effects

Question 35

nonselective steroidgenesis inhibitor drugs

Answer 35

-aminoglutethimide -ketoconazole