Cell signaling Pathways Steroid Hormoes Flashcards
what are steroid hormones synthesized from
cholesterol
describe the composition of steroid hormones
they are lipids that are fat soluble and hydrophobic
what are the two routes that steroid hormones use to exert their biological effects
a slower genomic response and a faster nongenomic mechanism
what receptors mediate genomic actions
nuclear receptors
what receptors exert nongenomic effects of steroid hormones
membrane receptors activate intracellular signaling pathways
describe the de novo synthesis of cholesterol
2 acetyl coA + acetoacetyl coA -> HMG CoA -> mevalonate ->isopentyl pyrophophsate-> geranyl pyrophosphate + farnesyl pyrophosphate ->squaliene -?lanosterol -> cholesterol
where do steroid hormones undergo structural changes
on side chains or inside of rings
what is estrogen derived from
testosterone and androgens
what catalyzes the synthesis of estrogen
aromatase
describe female progesterone levels
they change through puberty and adolescence (increase until menopause)
describe male levels of progesterone
relatively constant, low levels
what do plasma proteins do
bind and facilitate the circulation of lipid like hormones
what are some lipid soluble hormones that bind to members of the nuclear steroid/thyroxine receptor family
cortisol, retinoic acid, thyroxine
what is cortisol derived from
cholesterol
what is retinoic acid dervied from
metabolite of vitamin A1, doesnt have steroid ring structure
what is thyroxine derived from
tyrosine residues in thyroglobulin, does not have steroid ring structure
what are the domain structures of nuclear steroid receptors
variable region, DNA binding, hormone-binding
where are glucocorticoids synthesized
adrenal cortex
what do glucocorticoids do
regulate metabolism of glucose, stimulate transcription of anti-inflammatory proteins and factors
where is cortisol produced
zona fasciculata of the adrenal cortex
what type of steroid hormone is cortisol
glucocorticoid
when is cortisol released
in response to stress and a low level of blood glucose
what are the effects of cortisol
- increase blood sugar through gluconeogenesis
- suppress the immune system
- aid in metabolism of fat, proteins and carbs.
- decreases bone formation by causing osteocyte apoptosis
how are glucocorticoids used in low doses
in adrenal insufficiency
how are glucocorticoids used in high doses
-oral or inhaled glucocorticoids are used to suppress allergic, inflammatory and autoimmune disorders
-asthma
-post transplant immunosuppressants to prevent rejection and graft-versus-host disease
do glucocorticoids prevent infection
no
what is a side effect of glucocorticoid use
inhibit later reparative processes when given post transplant
how are glucocorticoids regulated
by corticotrophin releasing hormone by nerves in the hypothalamus stimulating ACTH which acts on the adrenal cortex to produce and release cortisol
how do glucocorticoids affect inflammatory responses (mechanism)
-Gc induces lipocortin which inhibits phosphatidyl choline from forming arachidonic acid.
- this then inhibits the formation of prostaglandins and thromboxanes by COX and subsequently inhibits vasodilation, capillary permeability and leukocyte attraction
- arachidonic acid not forming also inhibits the formation of leukotrienes which are subsequently inhibit phagocytosis, bacterial killing
how do glucocorticoids affect immune responses (mechanism)
- GC inhibits the formation of IL-1beta from macrophages which blocks fever and T-cell activation ->B-cell activation and thus antibody production
how do NSAIDs inhibit the synthesis of prostaglandins
NSAIDs inhibit cox 1 and cox 2 which alter the synthesis of thromboxanes and prostaglandins
what is osteoporosis
a skeletal disorder characterized by compromised bone strength, increasing the risk of bone fracture
how do decreasing estrogen levels affect BMD and fractures
-bone loss in women begins 2 years prior to last menses
-estrogen mediated bone loss is completed over 6 years
-bone loss from estrogen is from 6-12%
describe the rate of bone loss as a cause of estrogen decrease
steep decline at first then gradual decline
what is the connection between periodontitis and osteoporosis
shared risk factors such as age, genetics, hormone change, calcium, smoking, vitamin D
what is the function of selective estrogen receptor modulators (SERMS)
they compete with estrogen for the estrogen receptor so estrogen doesn’t bind
what are the androgens
DHEA, androstenedione, androstenediol, testosterone, DHT
what are the groups of steroid hormones
glucocorticoids, mineralocorticoids, androgens, estrogens, progesterone and vitamin D
what is an estrogen responsive element
specific short DNA sequence representing nuclear binding site for estrogen receptor protein and hormone complex
when are androgens clinically used
-male androgen insufficiency
-treatment of children with growth failure
-bone marrow stimulation in diseases resulting in hypoplastic or aplastic anemia
- masculinizing hormone therapy
what is the receptor for androgen
testosterone receptors
what is androgen insensitivity syndrome
mutations in the hormone binding region causing absence of hormone binding or changes leading to testicular feminization
what is the estrogen receptor associated with (think diseases)
breast cancer and other tumors, control of bone growth, osteoporosis, and uncontrolled growth of the male skeleton
what is generalized glucocorticoid resistance and symptoms
mutation in ligand binding domain of GR-alpha. presented with history of fatigue, anxiety, hyperandrogenism, and hypertension
how do steroid hormones circulate the blood
bound to specific binding or carrier proteins
how long do genomic actions take
hours to day
how long do non genomic effects take
minutes
describe the nuclear mechanism of glucocorticoids
-the GC enters the cytoplasm and binds a heat shock protein (hsp)
-the release of hsp causes the GC receptor to dimerize
-the dimer of the receptor and hormone enters the nucleus to bind to the response element
what are anabolic steroids
synthetic variants of testosterone
what are anabolic steroids used for therapeutically
to induce male puberty and treat cancer and AIDS
what are the health risks of using anabolic steroids
bad cholesterol levels, acne, high BP, liver damage, and changes in the left ventricle of the heart
what are the adverse effects of anabolic steroids
psychiatric symptoms like aggression, violence, mania, and less frequently psychosis and suicide
what is androgen insensitivity syndrome
mutations in the hormone binding region cause absence of hormone binding or changes leading to testicular feminization
what results in estrogen receptor alpha point mutations
breast cancer, endometrial cancer and some psychiatric diseases
what is generalized glucocorticoid resistance
mutation in ligand binding domain of GR. symptoms include fatigue, anxiety, hyperandrogenism, and hypertension
what are some diseases involved with mutations in the vitamin D receptor
rickets, alopecia, intervertebral disc disease, leprosy
what do agonists do and give example
bind to a steroid hormone receptor and trigger signaling pathways characteristic of the original hormone
ex: dianabol
what do antagonists do and give example
bind to the nuclear hormone receptors but do not trigger signaling pathways ex: tamoxifen and raloxifene (antagonists of estrogen receptor)
what are some environmental chemicals that target steroid hormone receptors
-bisphenol A in plastic bottles and plastic water pipes
- phytoestrogens in soy prodcuts
