Cell Signaling Pathways: Steroid Hormones Flashcards
what groups can steroids be grouped into based on their receptors? (7)
mineralocorticoids glucocorticoids androgens estrogens progesterones thyroid vitamin D3
what are natural steroid hormones synthesized form?
cholesterol
steroid hormones are lipids, which are fat soluble meaning they can
pass freely by diffusion through biological membranes and enter cells without a specific transporter mechanism
in the blood, because of their lipid or hydrophobic properties, steroid hormones circulate bound to
specific binding or carrier proteins rather than corticosteroid hormone binding globulin
steroids exert biological effects via two routes (2)
a slower genomic response (hours and longer)
faster nongenomic mechanism (minutes)
membrane associated receptors active
intracellular signaling pathways to bring about nongenomic actions of steroid hormones
nuclear receptors mediate genomic actions with time frames of
hours to days
concentration of estrogen in blood
male:
females (premenopausal):
females (postmenopausal):
male: 10-50 pg/ml
females (premenopausal): 30-400 pg/nl
females (postmenopausal): 0-30 pg/nl
concentration of testosterone in blood
males:
females:
males: 30-120 mg/nl
females: 2-8 ng/ml
concentration of progesterone in blood
males:
females premenopausal, follicular phase:
females premenopausal, luteal phase:
males: <1.0 ng/ml
females premenopausal, follicular phase: <0.70 ng/ml
females premenopausal, luteal phase: 2-20 ng/ml
plasma proteins bind and facilitate the circulation of
lipid like (hydrophobic) hormones
retuning acid binding protein binds to
retinoid acids
sex hormone binding globulin binds to
testosterone and estradiol
vitamin D binding protein binds
vitamin D
domain structures of nuclear steroid receptors (3)
variable region: what makes each receptor different
DNA binding domain: when hormone binds to receptor, this region reacts with DNA at hormone binding elements (specific sequence of nucleotides)
hormone-binding domains: bind to hormone
where are glucocorticoids synthesized
the adrenal cortex
glucocorticoids are a family of compounds which bind to the
GC receptor
the name glucocorticoid derives from its role in the regulation of the
metabolism of glucose
its synthesis in the adrenal cortex and its steroidal structure
what does glucocorticoids binding to their specific receptor stimulate?
transcription of anti-inflammatory proteins and factors
cortisol
natural steroid hormone, glucocorticoid
where is cortisol produced?
zona fasciculate of adrenal cortex
what is cortisol released in response to?
stress and a Leo level of blood glucose
primary functions of cortisol (3)
increase blood sugar through gulconeogenesis
suppress the immune system
aid in the metabolism of fat, protein, and carbohydrate
side effect if cortisol
decreases bone formation by causing osteocyte apoptosis (or autophagy at lower doses)
(neg effects on bone)
Nobel prize for synthetic corticosteroid
Drs. Kendall and Hence, Mayo Clinic; Professor Reichstein, Basel
glucocorticoids may be used in low doses in
adrenal insufficiency
are much higher doses, oral and inhaled glucocorticoids are used to suppress various (3) disorders
allergic]
inflammatory
autoimmune
inhaled glucocorticoids are the second line treatment for
asthma
glucocorticoids are administered as post-transplant immunosuppressants to prevent (2)
cute transplant rejection and the graft-versus-host-disease
glucocorticoids do not prevent an infection and also inhibit later
reparative processes
what is glucocorticoid synthesis is regulated by?
corticotrophin releasing hormone by nerves in the hypothalamus
corticotrophin releasing hormone stimulates the production of, —- which acts on the adrenal cortex to produce and release —
ACTH
cortisol
prostaglandin synthesis
NSAIDS Inuit COX1 and CO2, variably altering the synthesis of TXA2, PGI2, PGD2, and PGFalpha
TXA2: thromboxane A2
PGI2: prostacyclin
PGD2: prostaglandin
sex hormone target tissues (11)
breast female reproductive track male reproductive track bone vascular system CNS immune system skin kidney lung GI
osteoporosis
a skeletal disorder characterized by compromised bone strength predisposing a person to an increased risk of fracture
what does bone strength primarily reflect? (2)
the integration of bone quality and bone density
– million bone fractures annually
1.5
bone fractures can include (3)
hip fractures
vertebral fractures
wrist and other fractures
what are the annual consequences of hip fractures?
- -% will die from complications
- -% will require long-term care
24%
25%
worldwide:
- million hip fractures in 1990
- million hip fractures in 2050
1.7
6.3
lots of diseases are becoming an increasing burden on our aging probation
what percentage of women, on average, will suffer at least on osteoporotic fracture?
50%
how much did osteoporosis cost the US alone in 1997?
~14 billion
when does bone loss occur in menopausal women?
about two years prior to last menses
estrogen-deprivation bone loss is completed over - years
6
estrogen-deprivation bone loss ranges from about -% to -%
6-12%
men vs women, whole body BMC relative to baseline
men don’t have rapid bone loss, just a steady decline
SERM
selective estrogen receptor modulators
raloxifene
uses:
effects/location:
SERM
uses: osteoporosis, breast cancer
effects/location: agonist at bone; antagonist a breast and uterus
tamoxifen
uses:
effects/location:
SERM
uses: breast cancer
effects/location: agonist at bone and uterus; antagonist at breast
androgens (5)
DHEA androstendiol androstenedione testosterone DHT
clinical uses of androgens (5)
male androgen insufficiency
treatment of children with growth failure
bone marrow stimulation in diseases resulting in hypo plastic or aplastic anemia
masculinizing hormone therapy
anabolic steroids
familiar name for synthetic variants of testosterone
more properly termed anabolic-androgenic steroids
anabolic steroids were first synthesized in the 1930s, and are now used to
therapeutically induce male puberty and treat chronic wasting conditions such as cancer and AIDS
health risks of anabolic steroids include (5)
harmful changes in cholesterol levels acne high blood pressure liver damage changes in left ventricle of the heart
what are the adverse effects of anabolic steroids? (4)
significant psychiatric symptoms including aggression and violence, mania, and less frequently psychosis and suicide have been associated with steroid abuse (WWE wrestlers, weight lifters)
androgen insensitivity syndrome
mutations in the hormone binding region cause absence of hormone binding or qualitative/quantitative changes leading to testicular feminization or Reifenstein syndrome
Era point mutations have been found in (3)
breast cancer
endometrial cancer
psychiatric diseases
“famous” case reported in 1994 of a 28 year old male with incomplete epiphyseal closure, was 80.3 inches tall (still growing). he was found to have a mutation in the —- gene, which demonstrated the importance of
ESR1
estrogen in males
generalized glucocorticoid resistance
mutation in ligand binding domain of GR-alpha. presented with history of fatigue, anxiety, hyperandrogegism, and hypertension
hereditary diseases involving steroid hormone receptors and vitamin D receptor
hereditary vitamin Resistant rickets, alopecia, intervertebral disc disease, leprosy
definition of a non genomic action
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)
agonists
bind to a steroid hormone receptor and trigger signaling pathways characteristic of the original hormone
dianabol
synthetic agonist of the androgen receptor
membrane of nuclear hormone receptor family, stimulates expression of genes that enhance development of lean muscle mass (anabolic steroid)
antagonists
bind to the nuclear hormone receptors but do not trigger signaling pathways (like competitive inhibitors)
tamoxifen and raloxifene
antagonists of the estrogen receptor used in treating and preventing breast cancer because sone breast tumors rely on estrogen mediated pathways for growth. class of compounds, SERM
tropical issues (3)
environmental and food chemicals which bind to estrogen and testosterone receptors weakly
bisphenol Ai n plastic bottles and plastic water pipes
phytoestrogens in soy products
steroid hormones are synthesized from
cholesterol
steroids hormones act through — or — mechanisms
genomic or nongenomic
the classical mechanism is through interactions of steroids hormones with
nuclear receptors
membrane HR also exert modulatory effects on nuclear HR through signaling pathways targeting
nuclear HR and co-activators
membrane receptor binding of steroid hormones initiates various signaling pathways and activates other TF that can lead to transaction of some genes without
HREs
sex hormones or their analogs are used in the treatment of a variety of
diseases
analogs of sex hormones also have a number of — uses that can have serious side effects
recreational
