Biochem 2010 Venks Steroids #24-47

Front 1

24. Testosterone is transported by ______

Back 1

testosterone-estrogen-binding protein (TEBP)

Front 2

25. A plasma protein that binds nonspecifically to steroids is ________

Back 2

albumin

-transports proteins carry steroids from their site of synthesis to their site of action (target tissue)

Front 3

26. Name 2 compounds that inactivates steroids upon conjugation

Back 3

-in liver by conjugation with glucouronides or sulfates which are then excreted in the urine

-the donor compound for glucouronidation=UDP-glucouronate

-for sulfonation, 3'-phosphoadenosine 5'-phosphosulfate (PAPS)

Front 4

27. Receptors for FSH, LH, GnRH, Angiotensin II and III are located on
---------

Back 4

plasma membranes

Front 5

28. Receptors for cortisol and aldosterone are located in _______

Back 5

cytosol

Front 6

29. Receptors for testosterone, estrogen, and progesterone are located in _______

Back 6

Nucleus

Front 7

30. What are heat shock proteins (hsp)?

Back 7

receptors for cortisol (glucocorticoid) and aldosterone (mineralocorticoid) are usually bound to this cytosolic protein (90 kD)

-binding of steroid to receptor, the hsp dissociates

Front 8

31. Define hormone response element (HRE)

Back 8

-the region of the DNA onto which hormone-receptor complex binds

-share DNA sequence homology

-HREs that activate transcription are called positive response elements

Front 9

32 Glucocorticoid causes the repression of __________ gene

Back 9

the transcription of sepecific genes for proopiomelatnocortin (POMC)

-POMC contains the ACTH sequences

Front 10

33. The active conformation of the steroid hormone receptor is a dimer (true or false)

Back 10

True

-dimerization of the hormone-receptor complex is a prereq for efficient DNA binding

Front 11

34. Describe the DNA binding domain of hormone receptor

Back 11

-in the center of the receptor moiety

-shares 60-95% homology between steroid receptor classes

-has 2 zinc fingers, which facilitate binding to DNA near the transcription initiation complex

Front 12

35. What are zinc fingers?

Back 12

-second structures (4 cystein residues coordinated with zinc) that are formed in the DNA binding domain of the hormone receptor protein

-facilitate binding to DNA near the transcription initiation complex

Front 13

36. What is the secretion signals for aldosterone?

Back 13

angiotensin II/III

-secreted from glomerulosa cells

-target tissue: kidney

Front 14

36. What is the secretion signals for cortisol?

Back 14

pituitary adrenocorticotropic hormone (ACTH)

-from fasciculata cells of adrenal gland
-target muscle, liver, adipose tissue

Front 15

36. What is the secretion signals for testosterone?

Back 15

LH

-from leydig cells of testis

Front 16

36. What is the secretion signals for 17B-estradiol (estrogen)?

Back 16

-FSH

from the ovarian follicle and corpus luteum

Front 17

36. What is the secretion signals for progesterone?

Back 17

LH

-from the corpus luteum

Front 18

37. Name the bone forming and bone reabsorbing cells.

Back 18

forming --> osteoblast

resorbing --> osteoclast

-estrogens induce the synthesis of osteoprotegrin

Front 19

37. Name some bone antiresorptive compounds

Back 19

-bisphosphanates

-alendronate (Fosamax)

-Risedronate (Actonel)

Front 20

38. Name a catabolic product of estradiol that induces breast cancer

Back 20

16-Hydroxy estrogen (16-OHEN)

Front 21

39. What are the compounds that are being used in hormone replacement therapy (HRT)?

Back 21

-equine estrogen/medroxy progesterone (progestin)

-use for osteoporosis

Front 22

40. Name the universal sulfonate donor compound

Back 22

3'-phosphoadenosine 5'phosphosulfate
(PAPS)

Front 23

41. What happens if there is a deficiency in adrenal isoform of desmolase activity? Describe the clinical problems associated with this condition

Back 23

?

Front 24

42. Describe the biochemical basis of Congenital adrenal hyperplasia

Back 24

-results in insufficient cortisol production

-ACTH production is thererefore not feedback-inhib by cortisol and levels are very high and cause aderneal hyperplasia

-porgesterone accumulates and is channeled into the production of androgens, DHEA and androsteinedione

-->virilization in females, precocious sex organ development in prepubertal males, or diseases related to salt imbalance bc decreased levels of aldosterone

Front 25

42. Describe the biochemical basis of Addison's

Back 25

-overal deficiency of the adrenal steroid horomeones

-ACTH levels are always high

-pts are hypoglycemic due to decreased levels of gluconeogenesis bc of low cortisol levels

-low bp due to low levels of mineralocorticoids

-treatment: Hormone supplementation

Front 26

42. Describe the biochemical basis of Cushing's

Back 26

-prolonged exposure to glucocorticoid (either due to the usage of cortisol as an anti-inflammatory drug or due to tumors of adrenal cortex)

-results in elevated blood glucose levels

-pts have truncal obesity but have thin arms and legs, may have hypertension

Front 27

42. Describe the biochemical basis of Hypertension

Back 27

-excessive secretion of mineralcorticoids resulting from adrenal tumor results in hypertension

-treatment: aldosterone antagonists (spironolactone) forms inactive aldo receptors

-other drugs captopril, lisinopril, and enalapril which are small peptides that are competitive inhibs of ACE

Front 28

42. Describe the biochemical basis of Osteoporosis

Back 28

-major concern in post menopausal women

-estrogens induce the synthesis of osteoprotegrin, which causes osteoblast differentiation and suppress osteoclast

-use HRT

Front 29

42. Describe the biochemical basis of Testicular Feminization

Back 29

-genetic deficiency in 5a-reductase results in a decreased ability to reduce testosterone into the more potent DHT

-DHT in utero exerts androgenic effects male sexual differentiation

Front 30

43. Describe the role of fetal adrenal gland and fetal liver with reference steroid metabolism during pregnancy

Back 30

the fetal adrenal gland converts cholesterol to DHEA which is transported to the fetal liver to form 16a-hydroxy-DHEA

-this is converted to estrogen by aromatization

-thus co-operation between maternal and fetal tissue in maintaing proper levels of 17-B estradiol

Front 31

44. Describe the process of estrodiol mediated programmed cell death

Back 31

-blood levels of estradoil and progesterone drop, resulting in the sloughing of the endometerium, or menstration

-undergo apoptosis due to withdrawal of steroids

Front 32

45. Describe ANF mediated signaling

Back 32

-hypervolemia will generate ANF from heart atria

-binds to a specific zona glomerulosa cell membrane receptor and activates guanylate cyclase

-catalyzes the formation of cGMP from GTP

-cGMP antagonizes the synthesis and secretion of aldosterone

Front 33

46. Describe the key enzymes of the steroid metabolism (generic name sufficient)

Back 33

-cholesteryl esterase --> cleavage of cholesterol-ester into FA and cholesterol

-desmolase--> cleaves cholesterol side chain to generate pregnenolone

which other ones?

Front 34

47. Describe the mechanism of p-450 hydroxylase catalzyed reaction

Back 34

CYP stands for genes that encode for cytochrome P450 hydroxylase enzymes

-B-HSD = beta-hydroxysteroid dehydrogenase

ex cholesterol --> pregnenolone using desmolase