Cell Signaling Pathways: Steroid Hormones 9/15/21

Question 1

steroid hormones can be grouped into different types, based on receptors binding to what (7)?

Answer 1

glucocorticoids, mineralocorticoids, androgens, estrogens, progesterones, thyroid, and vitamin D3

Question 2

what are steroid hormones synthesized from?

Answer 2

cholesterol

Question 3

what are steroid hormones?

Answer 3

are lipids, which are fat soluble.

can pass freely by diffusion through biological membranes and enter cells without a specific transporter mechanism.

Question 4

how do steroid hormones circulate in blood?

Answer 4

bound to specific binding or carrier proteins rather than circulating free

Question 5

what are the two routes that steroids exert biological effects?

Answer 5

1. slower “genomic” response (hours and longer)

2. faster “nongenomic” mechanism (minutes).

Question 6

what mediates genomic actions hours to days?

Answer 6

nuclear receptor

Question 7

Membrane-associated receptors

Answer 7

activate intracellular signaling pathways to bring about nongenomic actions of steroid hormones.

Question 8

Biosynthesis of aldosterone

Answer 8

cholesterol->pregnenolone-> progesterone->deoxycortocosterone->corticosterone->aldosterone

Question 9

Biosynthesis of cortisol

Answer 9

cholesterol->pregnenolone-> progesterone-> deoxycortisol->cortisol

Question 10

Biosynthesis of dihyrotestosterone (DHT)

Answer 10

cholesterol->pregnenolone-> DHEA-> androstenedione->testosterone-> DHT

Question 11

Biosynthesis of estradiol (2 ways)

Answer 11

cholesterol->pregnenolone-> progesterone-> androstenedione->testosterone*-> Estradiol

OR

-> androstenedione->estrone*-> Estradiol

Question 12

Plasma proteins bind and facilitate the circulation of lipid (hydrophobic) hormones (3)

Answer 12

1. Retinoic acid binding protein binds retinoic acid
2. Sex hormone binding globulin binds testosterone and estradiol
3. Vitamin D binding protein binds vitamin D

Question 13

another word for estrogen

Answer 13

estradiol

Question 14

lipid hormones bind to nuclear steroid\thyroxine receptor superfamily (3)

Answer 14

1. Cholesterol -> cortisol
2. Metabolite of Vitamin A1->retinoic acid
3. synthesized from tyrosine & residues in thryoglobin -> thyroxine

Question 15

cortisol is synthesized from?

Answer 15

cholesterol

Question 16

Retinoic acid

Answer 16

a metabolic derivative of vitamin A that has powerful effects on limb bud development in embryos and skin renewal in adult mammals.

Question 17

Thyroxine

Answer 17

synthesized from tyrosine residues in the protein thyroglobulin in the thyroid gland.

Question 18

what are the 2 pathways in the simple model of steroid hormone action?

Answer 18

1. genomic (classical)

2. nongenomic

Question 19

overall domain structure of nuclear steroid receptors

Answer 19

variable region (amino acid identity)=DNA binding domain=hormoned binding domain

=: linked

Question 20

Response element

Answer 20

characteristic nucleotide sequences of the DNA sites that bind several major nuclear receptor

Question 21

where are glucocorticoids synthesized?

Answer 21

adrenal cortex

Question 22

glucocorticoids

Answer 22

(glucose + cortex + steroid) derives from its role in the regulation of the metabolism of glucose; Bind to specific receptor and stimulate transcription

Question 23

primary functions of glucocorticoids

Answer 23

increase blood sugar through gluconeogenesis, suppress the immune system, and aid the metabolism of fat, protein, and carbohydrate. It also decreases bone formation by causing osteocyte apoptosis (or autophagy at lower doses) as a side effect.

Question 24

how can glucocorticoids be used?

Answer 24

in low doses in adrenal insufficiency

Question 25

how are glucocorticoids used in higher doses?

Answer 25

oral or inhaled; to suppress various allergic, inflammatory, and autoimmune disorders. Inhaled glucocorticoids are the second-line treatment for asthma.

Question 26

how can glucocorticoids be administered?

Answer 26

post-transplant immunosuppressants to prevent cute transplant rejection and the graft-versus-host disease

Question 27

how is glucocorticoid regulated?

Answer 27

corticotrophin releasing hormone by nerves in the hypothalamus ultimately stimulating production of ACTH which acts on the adrenal cortex to produce and release cortisol

Question 28

osteoporosis

Answer 28

a skeletal disorder characterized by compromised bone strength predisposes in a person to an increased risk of fracture

Question 29

osteoporosis results in

Answer 29

``` - 1.5 Million Bone Fractures Annually Including Hip Fractures Vertebral Fractures Wrist and Other Fractures - Annual Consequences of Hip Fractures 24% will die from complications 25% will require long-term care ```

Question 30

Estrogen Effect on Bone Mineral Density (BMD) and fractures

Answer 30

- Change in BMD at menopause | - BMD decrease over tiem

Question 31

Shared risk factors for osteoporosis and periodontitis

Answer 31

age, genetics, hormone change, smoking, calcium, Vitamin D

Question 32

post-mendopausal osteoporsis

Answer 32

estrogen withdrawal, bone resorption, loss of trabecular strucutre, loss of skeletal strength, fracture

Question 33

Types of androgens

Answer 33

- Dehydroepiandrosterone (DHEA) - Androstenediol - Androstenedione - Testosterone (T) - 5α-Dihydrotestosterone (DHT)

Question 34

clinical use of androgens

Answer 34

- Male androgen insufficiency - Treatment of children with growth failure - Bone marrow stimulation in diseases resulting in hypoplastic or aplastic anemia. - Masculinizing hormone therapy

Question 35

Anabolic steroids used for?

Answer 35

sed therapeutically to induce male puberty and treat chronic wasting conditions such cancer and AIDS.

Question 36

Anabolic steroids risks

Answer 36

harmful changes in cholesterol levels, acne, high blood pressure, liver damage, and changes in left ventricle of the heart.

Question 37

Anabolic steroids adverse effects

Answer 37

significant psychiatric symptoms including aggression and violence, mania, and less frequently psychosis and suicide have been associated with steroid abuse (WWE wrestlers, weight lifters).

Question 38

Anabolic steroids are familiar to what?

Answer 38

testosterone

Question 39

Androgen insensitivity syndrome

Answer 39

mutations in androgen receptor (testosterone) cause absence of binding or qualitative/quantitative changes leading to testicular feminization or Reifenstein syndrome

Question 40

Estrogen receptor

Answer 40

Various ERα point mutations have been found in breast cancer, endometrial cancer and psychiatric diseases. “Famous” case reported in 1994 of a 28-year-old male with incomplete epiphyseal closure, was 80.3 inches tall (still growing). Found to have a mutation in ESR1 gene. Case demonstrated the importance of estrogen in males.

Question 41

Generalized glucocorticoid resistance

Answer 41

effect in glycocorticoid receptor; mutation in ligand binding domain of GR-alpha. Presented with history of fatigue, anxiety, hyperandrogenism, and hypertension

Question 42

Vitamin D receptor

Answer 42

Hereditary Vitamin D Resistant Rickets, Alopecia, Intervertebral Disc Disease, Leprosy

Question 43

Nongenomic Steroid Hormone Action

Answer 43

a response to receptor binding that does not initially influence gene expression, but involves signaling cascades (which may or may not result in gene expression changes).

Question 44

types (3) of steroid hormone receptors as targets for drugs

Answer 44

1. agonists 2. antagonists 3. topical issues

Question 45

agonists

Answer 45

bind to a steroid hormone receptor and trigger signaling pathways characteristic of the original hormone ex. dianabol

Question 46

antagonists

Answer 46

bind to the nuclear hormone receptors but do not trigger signaling pathways (like competitive inhibitors). ex. tamoxifen and raloifene

Question 47

Topical issues

Answer 47

Environmental and food chemicals which bind to estrogen and testosterone receptors weakly. ex. bisphenol, phytoestrogen

Question 48

Genomic Steroid Hormone Action

Answer 48

interactions of the steriod hormones with cytoplasmic or nuclear receptors. Hormone-receptor complexes bind to specific sequences in the DNA (hormone response elements, HRE) to effect gene expression