Term
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Definition
[image]
the 6 member rings are in the chair conformation and are trans fused
methyl group at 18 and 19 are on the same side of the molecule (beta)
[image]
up = beta (18 and 19 are always beta)
down = alpha
axial = outside the plane of the ring system
equatorial = on the same plane of the ring system
[image]
the rings are trans fused; each of the substituents on the fused system (bolded back bone) are opposite of each other (alpha, beta, alpha, beta...)
structure shown is in the anti conformation
the conformation of steroids is sterospecific |
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Term
conformation of progesterone
[image]
[image] |
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Definition
rings are trans fused (anti)
double bond at 4-5 |
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Term
| general structures of the sex steroids |
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Definition
[image]
estriol
estrogens are defined as having 18 carbons
ring A is aromatic so there cannot be a carbon 19
position 17 has an OH group
[image]
testosterone
androgens are defined as having 19 carbons
position 17 has an OH group
[image]
progesterone
progesterones are defined as having 21 carbons |
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Term
| steroid hormones: estrogens |
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Definition
[image]
18 carbons
aromatic ring A (exclusive to estrogens)
anti conformation
substituents at 3, 16, and 17
estradiol is the most potent, then estrone, then estriol
the receptor can accommodate different ring D conformations, but the structure does matter because binding is better for estradiol with a 17-OH
estradiol has low concentration
estrone has the highest concentration |
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Term
| female hormones: biosynthesis of estrogen |
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Definition
[image]
pregnenolone is the precursor to all the sex hormones
pregnenolone has a double bond in ring B
[image]
estrone is the precursor to estradiol and estriol
because of this, estrone is the most abundant |
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Term
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Definition
[image]
ALL of these molecules form congugates!
estriol and estradiol can be thought of as metabolites of estrone |
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Term
| female hormones: mode of action |
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Definition
reproductive tract, breast, and CNS
female reproductive system
estrogen receptor -> target cells
high affinity and low capacity: not many estrogen molecules can gain assess to the receptor
stereospecific
increase RNA synthesis in target cells
affect various enzyme systems
breast tissue:
stimulates proliferation of breast cells
promote growth of hormone-dependent carcinoma - estradiol stimulates gene expression and production of several proteins in breast cancer cells; progesterone receptors are induced by estrogens in breast cells
enzymatic activity increases in:
lactic dehydrogenase
beta-glucuronidase
alkaline phosphatase
peroxidase
glucose-6-phosphate dehydrogenase
plasminogen activator |
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Term
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Definition
[image]
4 defined regions:
transcription activation factor 1
DNA binding domain
ligand binding domain
transcription activating factor 2
2 estrogen receptors: alpha and beta
alpha is longer than beta, but both have the same regions
present in the whole body in different ratios, estrogens have the same binding affinity for both receptors
drugs may have different affinity for alpha or beta
located in the nucleus |
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Term
| binding of estrogens to the estrogen receptor |
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Definition
[image]
binding with estrogens:
electrostatic, hydrophobic, and dispersional interactions |
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Term
| estrogen's actions within a cell |
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Definition
[image]
estrogen enters the cell and interacts with the receptor (phosphorylation, conformational changes) forming the estrogen receptor complex
estrogen binds at the ligand binding domain of the estrogen receptor causing a conversion to homo and heterodimeric states
complex moves towards the nucleus and binds the estrogen responsive elements
ERE will form another complex (ERC = estrogen receptor complex)
ERC will bind DNA (or the ERC is part of the DNA)
transcription activation factor will be exposed and transcription will begin -> increased protein synthesis |
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Term
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Definition
[image]
order of activity when administered SUBCUTANEOUSLY: estradiol > estrone > estriol
order of activity when administered ORALLY: estriol > estradiol > estrone
orally, estradiol is metabolized very fast, so the bioavailability is very low
b/c of aromatic ring, estrogens are more planar than other sex hormones |
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Term
| progesterone biosynthesis |
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Definition
[image]
pregnenolone is the precursor
dehydrogenase and isomerase enzymes convert pregnenolone to progesterone |
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Term
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Definition
[image]
anything that has beta 5 gives an inactive compound; this region is very sensitive
all the compounds form conjugates (except progesterone b/c it doesn't have any OH groups) |
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Term
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Definition
[image]
progesterone binds to the receptor; undergoes conformational changes; binds to the responsive elements; expose the transcription activation factor; initiates transcription and protein synthesis |
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Term
| progesterone pharmacology |
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Definition
in the endometrium induces the secretory phase
in the myometrium stops the spontaneous rhythmic contractions of the uterus |
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Term
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Definition
androgens are synthesized in the testes and adrenal cortex
the most important androgen is testosterone
other male sex hormones: 5 alpha-dehydrotestosterone (more potent than testosterone)
FSH stimulates testosterone biosynthesis |
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Term
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Definition
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Term
| hypothalamus-pituitary-testicular axis |
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Definition
[image]
testosterone is secreted by the Leydig's cells and can act in a negative feedback fashion in the hypothalamus and pituitary to decrease the release of gonadotropins
testosterone is the precursor for DHT
testosterone is auto-regulated; increased synthesis when concentration is low, decreased synthesis when concentration is high |
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Term
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Definition
[image]
5-alpha-dihydrotestosterone
[image]
most metabolites are inactive (as far as androgenic effects) except starred molecules |
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Term
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Definition
[image]
AR = androgen receptor
PR = progesterone receptor
highly conserved by very selective |
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Term
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Definition
[image]
testosterone enters and interacts with receptors (testosterone can be converted to DHT); complex interacts with DNA through responsive element; activates transcription and protein synthesis |
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Term
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Definition
normal growth and development of male sex organs
retention of nitrogen and other inorganic substances (K, Ca, Cl, P, Na) = the anabolic effect
the actions of androgens (prostate, seminal vesicles, testis, and accessory structures) = the androgenic effect
androgens have 2 different functions: anabolic (related to cell growth/size) and androgenic (related to male characteristics) |
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Term
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Definition
physiological (androgen replacement therapy):
hypogonadism
pharmacological (non-gonadal disease):
anemia
osteoporosis
estrogen-receptor positive breast cancer
hereditary angioedema
immunological
pulmonary and muscular diseases |
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Term
| non-steroidal hormones (peptide hormones) |
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Definition
pituitary hormones:
growth and development
reproduction
responses to stress
intermediary metabolism
hypothalamic hormones and peripheral endocrine system
somatotropic hormones:
growth hormone
prolatin
placental lactogen
glycoprotein hormones:
luteinizing hormone
follicle stimulating hormone
human chorionic gonadotropin
thyroid stimulating hormone
POMC-derived hormones:
corticotropin
A-melanocyte-stimulating hormone |
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Term
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Definition
synthesized by:
lactotrophs in the anterior pituitary
brain
placenta, amnion, decidua, and uterus
mammary gland and milk
the immune system
3D structure is not elucidated
50% of aa are alph-helices, the rest form loops
secretion starts in the 5th week of gestation
low levels in males
levels elevate in normal cycling females |
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Term
| prolactin biological actions |
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Definition
reproduction:
lactation
luteal function
reproductive behavior
homeostasis:
immune response
osmoregulation
angiogenesis |
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Term
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Definition
hypothalamic or pituitary disease:
inhibitory dopaminergic signals
dopamine agonists cause a decrease in prolactin
hyperprolactinemia by prolactin-secreting adenomes:
in women - galactorrhea, amenorrhea, and infertility
in men - loss of libido, impotence, and infertility |
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Term
| follicle stimulating hormone |
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Definition
[image]
FSH receptor is a GPCR
signaling cascade activates adenylyl cyclase and PKA -> activation of aromatase (transforms testosterones into estrogens)
FSH is directly related to the production of estrogens
FSH increases mitosis and production of the LH receptor
FSH is a stimulator of granulosa cell proliferation |
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Term
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Definition
[image]
LH receptor is a GCPR
LH binds and will initiate a cascade that will increase the expression of PKA -> increase production of progesterone
LH will increase progesterone and will stimulate the production of androgens
FSH is mainly related to estrogens; LH is mainly related to progesterones and androgens |
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