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194 Cards in this Set

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ACTH is cleaved from
"ups your steroids, gives you some pigment, thins you down, and makes you feel good"
stimulates release of ACTH
Physical or emotional stress
increases glucocorticoid production by the adrenal gland
act on gonads to inhibit stimulation by estrogen or testosterone
Increased __ feedback to the hypothalamus decreases GnRH secretion, which in turn leads to lower secretion of LH
leads to decreased fertility in both men and women.
Low LH
is equivalent to stress and can result in amenorea or in anovulation
extensive exercise
regulates steroid synthesis (rather than secretion) by the Adrenal Cortex.
ACTH promotes the “fight or flight” response by stimulating synthesis of:
glucocorticoids, mineralcoritcoids, and androgen precursors
increase glucose production, inhibit
protein synthesis, increase protein breakdown stimulate lipolysis,
and turn down the immune response
Glucocorticoids, such as cortisol and hydrocortisone
promote water retention and thereby increase blood volume and blood pressure
Mineralcorticoids, such as aldosterone
provide hormones such as testosterone, which may help provide an increased aggressive attitude to cope with the stress
Androgen precursors
Too much ACTH leads to
Cushing’s disease
leading endogenous cause of Cushing’s disease:
benign pituitary adenoma (70%)
Endogenous causes of Cushing’s disease
tumors (30%)
benign pituitary adenoma (70%)
Exogenous cause of Cushing's disease:
OD of ingested corticosteroids (most common cause of the disease)
Too little ACTH leads to symptoms of
Addison’s disease
Addison’s disease itself is the result of a “primary” loss of function of the
adrenal gland
drug formulation of ACTH, Acthar = a brand name
limited use to decrease immune system
function; been used to alleviate exacerbations of multiple sclerosis and
myasthenia gravis
cheaper to make than the 39 AA full length ACTH corticotrpin
Cosyntropin (cortrosyn) = 24 AA synthetic peptide
If the body makes little or nothing
of some normally endogenous peptide, when that peptide is administered exogenously...
the body’s immune system mounts an immune response against it, which may present as an allergic reaction.
primary use of Cosyntropin
diagnostic, (short half-life)
LH and FSH are from the
Human chorionic gonadotropin (hCG) is from the
LH, FSH, and HcG are composed of
two peptide chains (subunits) alpha and beta
all of the 3 gonadotropins have two subunits, the alpha subunit has __ AA's and
92; identical for all three
specificity of gonadotropins is conferred by the __ subunits
The homology between the first 115 AA in the beta chains of gonadotropins LH and CG is __ .
The alpha and beta chains of gonadoptropins interact with each other by __ interactions, with NO inter-chain S-S bridges.
ionic and hydrophobic
Both subunits of the are __
glycosylated (sugar residues contribute between 16% and 30% of the total mass of the hormones).
Two main functions of the carbohydrate (the glycosylated portion of the gonadotropin)
removal of one of the three carbohydrate groups in __ (beta chain has 2; alpha chain has 1) reduces half-life from 90 minutes down to 2-3 minutes.
what type of affinity do gonadotropins have for their receptors?
very high
To achieve half of the maximum
response, only 1% of the receptors need to be occupied.
occurs by endocytosis or decreased rates of synthesis, or both mechanisms
receptors become desensitized
Promotes development and maturation of ovarian follicles
Stimulates ESTROGEN synthesis and secretion by the ovarian follicles
Stimulates maturation of sperm and testicular development
contributes to the final maturation and development of both the
follicle and the ovum that it contains.
Promotes conversion of the ruptured follicle to become a corpus luteum
produces its own estrogen and subsequently progesterone.
corpus luteum
Progesterone exerts negative feedback on the __ to decrease the production of LH and thus prevent further follicle and ovum development until progesterone levels subside at
the end of the menstrual cycle.
pituitary (and hypothalamus)
If no positive stimulus to the corpus luteum is received from placental hCG within 7 days, the corpus luteum begins to __.
shrink and degenerate
Re-initiation of the menstrual cycle occurs because low levels of estrogen and progesterone stimulate
the hypothalamus to increase secretion of GnRH
increased GnRH stimulates the anterior pituitary to release increased amounts of __.
FSH and LH
stimulates synthesis and secretion of androgens, especially testosterone, by the testes
when pregnancy occurs ( >7 days after ovulation) __ stimulates the ovarian corpus luteum to secrete high levels of estrogen and progesterone
Therapeutic use of CG
stimulates ovulation
a 1:1 ratio of FSH and LH, following their purification from the urine of postmenopausal women, called “menotropins”
Usage of Pergonal in women
admin for 7-12 days to promote growth of the ovarian follicle to enhance fertility
Pergonal works only if women don’t produce adequate levels __ of on their own.
hCG must be administered once the __ in order to induce ovulation and permit pregnancy.
follicles are mature
Administered for at least 3 months to induce spermatogenesis for men
who don’t produce sufficient gonadotropins
it is FSH ONLY, purified from urine of postmenopausal women
Urofollitropin is aka
Administered early in the follicular phase to promote follicle development,
especially for women who ovulate but whose fallopian tubes are too narrow to allow the egg to pass.
It is also used for women with polycystic ovary syndrome (PCOS), where ovaries are enlarged, but follicles remain very small. Often used for in vitro fertilization.
a synthetic FSH (so no trace amounts of LH are possible). Tends to have a
relatively low pH (acidic).
For males, can be used
if the testes are OK, but pituitary secretion of gonadotropins is inadequate.
a synthetic FSH, but with a different pattern of sugars so it has a higher
Profasi, Pregnyl
Purified from the urine of pregnant women.
Administered to stimulate ovulation in women who lack function in their anterior pituitary and cannot secrete LH.
can also be used for cases of hypogonadism (insufficient development of the reproductive organs).
If the reproductive problem is due to pituitary dysfunction, this condition may be called
"hypogonadotrophic hypogonadism"
where during childhood the testicles don’t descend into the scrotum.
Choriogonadotropin alpha is aka
This is the recombinant DNA product identical to hCG, which is now becoming less costly to obtain relative to purifying hCG from urine.
these hormones are synthesized in the
hypothalamus and then moved along the neuronal axons to the posterior pituitary cells
ADH and oxytocin
Each chain has a carbohydrate side
chain coupled through AA Asparagine (Asn).
sugar function
stability and recognition
Diagnostic, to determine whether a thyroid problem is primarily at the thyroid itself
or whether the problem is with the pituitary gland.
treatment of hypothyroidism if the thyroid is causing the problem
direct admin of t3 or t4 (thyroxin) - TSH admin would not increase thyroxin
in secondary hypothyroidism the primary defect is at the
anterior pituitary
treatment for secondary hypothyroidism
admin of TSH to increase the release of thyroxine
to rule out a tertiary hypothyroidism, TRH could be given to determine whether
TSH is secreted from the __.
helps the kidneys retain water, in order to control the osmolarity of the blood
at high concentrations, __ causes arterioles and capillaries to contract (especially coronary vessels),
which increases local blood pressure
ADH is aka
defined by the concentration of ligand required for occupancy at equilibrium of half of the available receptors
receptor AFFINITY
corresponds to a very low number, such as picomolar,
high affinity
corresponds to a higher number, such as micromolar or millimolar
low affinity
is NOT recommended for treating low blood pressure, since it affects coronary vessels
how to treat hypotension
increase peripheral resistance; do not work directly on the heart because of the corresponding stress
stimulates muscles in the uterus to contract
This hormone is secreted during
labor to cause delivery of the fetus
stimulates contraction of smooth muscle in the mammary
glands, which causes milk to be squeezed out of the alveoli (small sacs) so it can enter larger cavities
(sinuses) for release to the baby.
__ causes alveoli to fill (let-down), whereas __ causes alveoli to empty (secretion)
prolactin, oxytocin
These two hormones each consist of 9 AA
oxytocin and ADH
both hormones have their C-terminal AA blocked by amidation (CONH2).
ADH and oxytocin
has Phe 3 and Arg 8
has Ile 3 and Leu 8
both ADH and oxytocin have this residue at position 2
Steric hinderance indicates that receptors for ADH and oxytocin are similar in the region that will recognize Tyr 2, but different in the region that will recognize
positon 3
synthetic form of ADH with Arg replaced with Lys
Pintocin is aka
a synthetic peptide given only with strict medical supervision (in a
hospital) to induce labor/delivery
It can also be used to speed up the delivery of the placenta following delivery of a baby.
a synthetic peptide that can be given as a nasal spray. It is used to treat a form of diabetes called diabetes insipidus
where pituitary release of ADH
doesn’t occur properly, resulting in the loss of water retention, extreme thirst, and dehydration
“diabetes insipidus”
a synthetic peptide that can also be given as a nasal spray, or orally, or
parenterally. It is also used to treat the symptoms of diabetes insipidus
used to treat children who
experience uncontrolled bed-wetting.
It differs structurally from ADH in that the N-terminal amino group of Cys 1 has been removed, and the L-Arg 8 has been replaced with a D-Arg
The structural abbreviation is dDAVP
lypressin with three Gly AA’s coupled in front of N-terminal Cys 1
It is given to treat bleeding of the esophagus that may result from cirrhosis of the liver.
posterior pituitary hormones
oxytocin and ADH
two main hormones secreted by the thyroid gland
t3 (tri) and t4 (thyroxine)
a segment of a large protein called thyroglobulin
Main component of thyriod gland =
is like a bag of
grapes (acinar = Latin for “grape”), with each grape being a follicle.
Promote release of T4 and T3 from thyroid gland
Stimulate uptake of iodide (I - ) from blood into acinar cells.
Even under normal conditions, __ is pumped into the cells against a 20:1 concentration
Under excess __ stimulation, iodide can enter against a gradient > 100:1.
Enzyme that puts iodide onto tyrosine =
thyroid peroxidase
requires H2O2 as a cofactor; so named because it gets energy for aromatic halogenation by cleaving peroxide
thyroid peroxidase
Since __ are quite insoluble, to move through the circulation, they adsorb to one or more of three plasma proteins
T4 and T3
carries about 3/4 of all T4 and T3
Thyroxin-binding globulin
also called T4–binding pre-albumin
It has an affinity 1000 times less affinity for T4 than thyroxin-binding globulin
caries only 10% of T4, but about 30% of T3
has four identical subunits with a funnel-shaped opening at one end
Principal receptors for t3 and t4 are here
in nucleus of cells
MSH, ACTH, LPH, and endorphins are all prodcuts of the enzymatic cleavage of
the primary reason why drugs that mimic CRH have not been developed
the diversity of the peptide products derived from the enzymatic cleavage of POMC - (and their many functions)
ACTH and b-endorphins act on different pathways to
diminish fertility
inhibit GnRH release and CRH release as well
inhibition of GnRH by estrogen is this type of response
lowered CRH release by estrogens is
diminished POMC processing and thereby lower ACTH and b-endorphin secretion
the reasoning behind use of corticotropin for autoimmune disease over more powerful steroidal drugs which provide faster relief
more ADRS
in females, LH
induces ovulation
once there is a sharp increase in estrogen, about a day later, there is a simultaneous release of FSH and LH from the AP which
promote the rupture of the follicle and the release of the ova
with promoting by LH, this later becomes the corpus luteum
the ruptured follice which releases the ova
the loss costly analog of hCG which has the same applications
Similar to the gonadotropins, __ has two peptide subunits held
together by noncovalent (ionic and hydrophobic) interactions.
Each chain of TSH has a carbohydrate side chain coupled through this AA
Asparagine (Asn)
admin product of TSH
Diagnostic, to determine whether a thyroid problem is primarily at the thyroid itself
or whether the problem is with the pituitary gland.
If the primary defect causing hypothyroidism is in the thyroid, treat with
direct admin of T3 / T4 (thyroxine)
if the primary defect is at the anterior pituitary (secondary hypothyroidism), treat with
admin of TSH
enhances release of thyroxine
to rule out a tertiary hypothyroidism, __ could be given to determine whether __ is secreted from the pituitary.
two hormones released from the PP
ADH and oxytocin
since vasopressin activity occurs only at high concentrations, this suggests
different affinities by different target cells for the ADH
both form a ring by virtue of S-S bridge btw CYS residues at positions 1 and 6
ADH and Oxytocin
convulsions which accompany pregnancy-induced hypertension (a leading cause of death to mother or child in underdeveloped countries)
a segment of a large protein called thyroglobulin
formed by the conjugation of two diiodinated
(or one di- and one mono-iodinated) tyrosine residues within thyroglobulin
Main component of gland = follicles
are secreted into the lumen for storage of hormone precursors
thyroglobulin and hypoiodic acid
When more thyroid hormones are needed by the body, __ carrying the hormones is pulled back into the cell at this surface by endocytosis
must occur before thyroid hormones are secreted into the bloodstream for transport
thyroid hormones must be chopped off of thyroglobulin
About one-third of the total weight of the whole thyroid gland is due just to the amount of
Promote release of T4 and T3 from thyroid gland
Stimulate uptake of iodide (I-) from blood into acinar cells.
Under excess __ stimulation, iodide can enter against a gradient > 100:1
Enzyme that puts iodide onto tyrosine
thyroid peroxidase
requires H2O2 as a cofactor
thyroid peroxidase
Iodine enters the lumen of the
follicle as
Its other function is to couple either two DIT’s or a DIT and an MIT to form Tg-bound T4 or T3
thyroid peroxidase
From a single Tg molecule, only __ hormones are released.
2 to 5
Since T4 and T3 are quite insoluble, to move through the circulation, they
adsorb to one or more of three
plasma proteins
Even with a bound T4, transthyretin also binds
four molecules of Vitamin A
About 80% of T3 __
comes from in the peripheral tissues (especially liver and kidney).
removal of iodide from T4
it only carries one of the hormones (T4)
Principal T3 / T4 receptors are here
in nucleus of cells
The main result of thyroid hormones binding to nuclear receptor proteins is to
stimulate transcription of a variety of genes, resulting in increased production of proteins.
lack of hormone from thyroid causes increased release of TSH, that
stimulates the thyroid to enlarge in an effort to compensate
“Non-toxic” Goiter
may be due to lack of I2 in diet
non-toxic goiter
A lack of iodine during early childhood means lack of CNS development (mental
retardation) and a stunting of growth due to abnormal bone formation
Lack of iodine, or loss of the thyroid, or lack of TSH can cause
mucopolysaccharide infiltration of the spaces between cells of the skin and muscle.
The tongue
can become thicker, also the hands and face become puffy. Anemia and mental apathy,
sensitivity to cold are also symptoms.
1. Increased heart rate; increased cardiac output
2. Anorexia (excess catabolism)
3. Poor thermoregulation (excessive heat, sweating)
4. “Toxic” goiter (from inflammation)
Autoantibodies against one’s own TSH receptors on acinar cells of the thyroid lead to an overproduction and release of T4 and T3
Graves’ Disease
Autoantibodies against Tg or other thyroid cell proteins lead to infiltration of cytotoxic T-cells
Hashimoto’s Disease
plug up the machinery needed for iodine uptake and incorporation to
Hashimoto’s Disease
Somet hyroid cancers: are due to exposure to
radioactive iodine
treatment for hypothyroidism
hormone replacement
treatment for hyperthyroidism
hormone ANTAGONIST to block the peroxidase enzyme so that less
hormone is made
prodrug of MMI that is converted to MMI in vivo
Bile acids are primarily synthesized in the liver from
an intermediate in the synthesis of all the steroid hormones
stimulates formation of pregnenolone.
ACTH from Ant. Pitu.
two hydroxylation steps (at C20 and C22), followed by cleavage of the side chain in front of C22 by
enzyme = desmolase
primarily made by the corpus luteum and the placenta
Four steps, from progesterone: three additions of -OH (C17, then
C11, C21, = cortisol), then oxidation
hydroxylate and cleave side chain
aldosterone, from progesterone:
3 oh'ns followed by oxidation
If reduce the ∆4 double bond of an androgen, you get 5α dihydrotestosterone, a
more potent androgen
estradiol, from testosterone:
1) clip the C19 methyl
2) reduce the 3=O to 3-OH;
3) aromatize the A ring.
Steps require NADPH + O2
Steps require NADPH + O2
formation of estradiol from testosterone