Name______________________________
Instructions: There are 100 points on this exam. The exam has
5 pages. Everyone must answer questions #1-#5. You then have a choice:
answer 1 of the 3 essays, #6-#8. Budget your time and good luck.
Multiple Choice: circle all that are true/correct. 40 points, 2 points
each response.
1. If a biological response to an organ extract requires hours to days
to occur, what group of hormones would you attempt to purify first to identify
the hormone responsible?
a) amino acid derivative neurotransmitters
b) prostaglandins
c) small peptides
d) steroids
e) proteins
2. Hormones are always
a) proteins that have carbohydrates on their surfaces
b) specific chemical compounds that can be isolated
c) bound to serum carrier proteins
d) produced by one cell and carried via blood serum to act on another
cell
e) present in serum in concentrations above 10 micromolar
f) produced continuously by their cells of origin
g) capable of generating cellular responses within milliseconds of binding
to cell receptors
h) involved when tissues respond at the cell level
i) absolutely specific in their binding to receptors
j) unique to the species from which they are isolated, they cannot act
in other species.
3. All the transduction mechanisms (hormone action mechanisms) studied
thus far directly involve ATP during the activation of cellular response
except
a) the adenylate cyclase pathway
b) the protein kinase C portion of the phosphoinositide turnover mechanism
c) the tyrosine kinase mechanism
d) the nuclear ("steroid") receptor mechanism
e) the G-protein-stimulated opening of membrane K+ or Ca++
ion channels.
4. Previously uncharacterized hormone receptors might be purified from
among the proteins generated in a broken-cell RNA translation experiment.
They could be identified as receptors by:
a) their molecular size
b) their ability to bind radioactively labeled hormones only if the
concentration of non-radiolabeled hormones (of the same types) are very
low
c) their tendency to become radiolabeled with phosphate in the presence
of hormone; and ADP-O-32PO3 (-phosphate labeled ATP)
d) their tendency to be removed from solution by surfaces to which hormone
agonists have covalently attached
e) their ionic charge (isoelectric point).
5. Prolactin, thyrotopin and somatotropin are:
a) all produced in the adenohypophysis
b) all controlled by somatostatin, GRH and epinephrine
c) all controlled by somatostatin and TRH
d) all help maintain processes essential to mammalian growth
e) all share similar alpha subunits
6. A chemical communication system must possess the following elements:
a) a signal, a medium, a receptor, a transducer, a transformer and a
recorder
b) a signal, a medium, a receptor, a transducer, and a rectifier
c) a signal, a medium, a receiver, a transducer, and a response element
d) a signal, a receiver, an accelerator, and a brake
e) a signal, a receiver, a transducer, and a sender
7. The definition of a hormone must be empirical or operational because:
a) we cannot synthesize hormones in large enough quantities to study
them.
b) a signal means nothing in the absence of a decoder.
c) by definition a hormone must act on a cell distant from its site
of synthesis.
d) immunoassays only measure biological activities of hormones.
e) it is impossible to hear the sound of one hand clapping.
8. Adenylate cyclase:
a) is the enzyme responsible for the generation of cAMP from ATP.
b) can be both stimulated and inhibited by GTP-binding proteins.
c) helps to mediate the production of a cellular response to hormone
binding.
d) is located within the nucleus of the cell.
e) binds to the beta subunit of Gs subsequent to hormone
binding to receptor.
9. Luteinizing hormone, follicle-stimulating hormone and chorionic gonadotropin:
a) all stimulate gametogenesis in both the male and female.
b) all are secreted proteins.
c) all possess the same beta subunit within a species.
d) all act via cyclic-3',5'-adenosine monophosphate mediated mechanisms.
e) each act on distinct cell types.
10. The hypothalamus
a) lies at the base of the brain and surrounds part of the third ventricle.
b) produces both stimulatory and inhibitory peptides.
c) contains several different groupings (nuclei) of neuroendocrine cells.
d) supplies factors to the pituitary via the portal plexus.
e) does not receive inputs from the thalamus or cortex of the brain.
11. Hormone receptors
a) can be saturated with exogenous hormone.
b) are always proteins.
c) are highly specific for a given hormone.
d) for multiple proteins can coexist on the membrane of the same cell.
e) remain at constant levels on single target cells at all times.
12. Changes in the levels of circulating hormones
a) closely reflect alterations in hormone receptor turnover rates.
b) occur on a time scale of seconds to hours depending on the hormone.
c) only result from gradual shifts in hormone clearance by the liver.
d) reflect the frequency of pulsatile release by the cells of synthesis.
e) reflect the amplitude of pulses released by the cells of synthesis.
13. ACTH production is controlled by:
a) positive stimulation by CRH from the basal hypothalamus
b) negative stimulation by dopamine from the basal hypothalamus
c) negative stimulation by glucocorticoids from the adrenal medulla
d) negative feedback of mineralocorticoids on the corticotropes
e) positive stimulation by TRH from the neurohypophysis
f) selective hydrolysis of a large peptide precursor
g) clearance rate of circulating ACTH
h) clearance rate of circulating adrenal cortical steroids
i) negative feedback by MSH onto the basal hypothalamus
j) neural stimuli that result in production of endogenous opioids
14. The following elements in a hormonal system involving the hypothalamus
may vary from hour to hour.
a) receptor affinities (Ka) for hormone
b) serum hormone levels
c) concentrations of hormone binding/carrier protein in serum
d) receptor numbers for hormone on target cells
e) levels of phosphorylated proteins found in target cells
f) transducer activity levels in target cells
g) releasing hormone levels in pituitary portal circulation
h) gene transcription activity in neuroendocrine cells of the hypothalamus
i) rate of synthesis of hormone by pituitary cells producing it
j) the rate at which hormone is broken down by specific degradation
systems
15. The following are necessary to successful generation of a response
in a steroid target tissue.
a) receptor-mediated endocytosis
b) specific heat-shock protein recognition sites on DNA
c) specific steroid-receptor recognition sites on DNA
d) down regulation
e) protein kinase C
16. The following elements in the testicular-hypothalamic-gonadotrope
system may vary from hour to hour.
a) serum testosterone levels
b) LHRH levels in portal circulation
c) receptor numbers for LH on the Leydig cells
d) the level of positive feedback of testosterone on gonadotropes
e) transducer activity levels in Sertoli cells
f) LH receptor affinities (Ka) for LH
g) gene transcription activity in neuroendocrine cells of the medial
basal hypothalamus
h) concentrations of androgen binding protein
i) circulating luteinizing hormone levels
j) gonadotrope secretion of LH
17. The definition of a hormone is:
a) an historical accident
b) based on interactions with antibodies
c) always "a substance produced by one cell and secreted into the bloodstream
to act on a distant cell of a second type"
d) "something that stimulates"
e) empirical and must include description of the molecule and the effects
of its absence
f) always very different from the definition of a nutrient
g) virtually identical to the definition of a chemical regulator produced
by one bacterium to alter the function of another bacterium
h) distinct from the definition of a neurotransmitter
i) ultimately dependent on the existence of a specific cellular transduction
system
j) the reason bioassays are required in endocrine science
18. Prolactin, thyrotopin and somatotropin are:
a) all produced in the neurohypophysis
b) all share similar alpha subunits
c) all controlled by somatostatin and TRH
d) all help maintain processes essential to mammalian growth
e) all controlled by somatostatin, GRH and serotonin
19. Luteinizing hormone, follicle-stimulating hormone and chorionic
gonadotropin:
a) each act on distinct cell types.
b) all are glycoproteins.
c) all act via cyclic-3',5'-adenosine monophosphate mediated mechanisms.
d) all stimulate gametogenesis in both the male and female.
e) all possess the same beta subunit within a species.
20. The hypothalamus
a) produces both stimulatory and inhibitory peptides.
b) lies at the base of the brain and surrounds part of the second ventricle.
c) supplies factors to the pituitary via the portal plexus.
d) contains several different groupings (nuclei) of neuroendocrine cells.
e) receives inputs from the both the thalamus and the cortex of the
brain.
21. If a biological response to an organ extract requires seconds to
minutes to occur, what group of hormones would you attempt to purify last
to identify the hormone responsible?
a) amino acid derivative neurotransmitters
b) prostaglandins
c) small peptides
d) steroids
e) proteins
22. The mechanisms of action of PRL and GH:
a) involve membrane-bound receptors
b) are probably related
c) involve activation of adenylate cyclase
d) are very much like those of thyroxine and corticotropin
e) are well known
23. ACTH levels are controlled by:
a) negative stimulation of corticotropes by CRH from the basal hypothalamus
b) negative feedback of mineralocorticoids on corticotropes
c) positive stimulation of corticotropes by TRH from the neurohypophysis
d) clearance rate of circulating ACTH
e) neural stimuli that result in production of endogenous opioids
4. T/F Briefly, defend your answer. 30 points, 3 points each; 1 point for T/F, 2 points for defense.
T F a) All hormones are proteins.
T F b) Immunoassays provide the same information as bioassays.
T F c) Hormone secretion never occurs without a stimulating agonist.
T F d) Endocrinology as a science absolutely requires bioassays.
T F e) All endocrine stimuli result from secretions within the body.
T F f) Responses to a given hormone stimulus are always the same.
T F g) Female gamete production depends only on LH levels.
T F h) The major control of PRL is somatostatin.
T F i) Hormone receptors must be specific for a single hormone but need
not bind tightly less they unduly prolong hormonal actions.
T F j) Responses to hormones, e.g., rise in blood glucose, result only
from changes in hormone breakdown or receptor "down-regulation."
T F a) Cells that produce hormones release these hormones at constant
levels over time.
T F b) Receptors for a specific hormone are found in only limited numbers
on target cells.
T F d) Hormones can be classified in one of three groups: proteins,
lipids, or gases.
T F e) Circulating hormone levels are only determined by the rate of
hormone synthesis.
T F g) Heat shock proteins are mostly involved in moving Ca++
around the cell cytoplasm.
T F h) A hormone can only be defined in the presence of the isolated
and purified hormone receptor.
T F i) Endocrinology could not exist if chemical assays were the only
means by which to identify hormonal molecules.
T F j) An endocrine disease condition (endocrinopathy) can be induced
only by loss of circulating hormone.
3. The definition of a hormone:
T F a) is an historical accident
T F b) is based on interactions with antibodies
T F c) is always "a substance produced by one cell and secreted into
the blood to act on a distant cell of a second type"
T F d) is simply "something that stimulates"
T F e) must include description of the molecule and the effects of itsabsence
T F f) is always very different from the definition of a nutrient
T F g) is not possible without reference to a biological system
T F h) is distinct from the definition of a neurotransmitter
T F i) is dependent on the existence of a specific cellular transduction
system
T F j) applies to all those chemicals that circulate in the body at
concentrations below microgram levels
Essay. (15 points) Choose one of the three given.
4. The ratio of biological potency per unit mass of FSH over immunological
reactivity per unit mass of FSH changes over the course of a man's lifetime.
The ratio changes during aging when the testes cease optimal function in
the production of steroids and gametes. What would you expect the pattern
of FSH secretion to do during old age in terms of both immunological and
bioassayable FSH? Provide a reason for the difference between the two measures
of FSH in this situation.
7. A patient walks in to a physician's office complaining of chronic
hyperexcitability, inability to adapt to changes in room temperature, loss
of weight in spite of a voracious appetite, and of a swelling near the
base of the throat. The physician suggests there is probably a hyperfunction
in the "thyroid-axis" resulting in elevated responses by thyroid sensitive
tissues. He orders measurements of serum thyrotropin (TSH, the pituitary
hormone that stimulates the thyroid), serum thyroxine (the hormonal product
of the thyroid), serum thyroxine-binding globulin (TBG, the protein that
binds most thyroxine in circulation and determines the amounts of free
hormone available to cells), and serum "reverse" triiodothyronine (a compound
formed during breakdown of thyroxine) on each of four blood samples taken
at four different times of day. Why (other than legal protection for himself
in making the diagnosis) does the physician order each of these tests?
What major source of the patient's problems could he miss using only these
tests?
8. In New Guinea we have found a population of humans that demonstrates
high levels of thyroxine-binding globulin and high levels of albumin in
serum in addition to normal total thyroxine levels in serum. Sex hormone
binding globulin (SHBG) can be used as an in vivo bioassay or "index" for
free thyroxine in serum; SHBG goes up when free thyroxine is high and SHBG
goes down when free thyroxine is low. From the above comments should we
expect SHBG levels to be high or low in our New Guineans? If we found the
levels of SHBG and free thyroxine to also be normal, what could we say
about biochemical properties of which serum binding protein(s)?
3. It has been known for some time that estrogens have a stimulatory
effect on ovarian follicular growth and oocyte maturation. Indeed, their
presence is absolutely required for ovarian gametogenesis in all animal
species thus far examined. Only recently, however, have antibodies become
available that are directed against the isolated, purified estrogen receptor
protein which is normally isolated from chickens or cattle. These antibodies
have been used to successfully localize estrogen receptors within the nuclei
of cells in uterine endometrium from a wide variety of species including
humans and other primates. Interestingly, however, localization experiments
performed using these same antibodies on ovarian follicular cells under
a broad variety of conditions proved negative. These cells appear in these
experiments to be devoid of estrogen receptors. Suggest at least one plausible
explanation for these findings.
4. The ratio of biological potency per unit mass of LH over immunological
reactivity per unit mass of LH changes over the course of a woman's ovarian
cycle. Likewise, the ratio also changes during the course of menopause
during which the ovaries cease to function in the production of steroids
and gametes. What would you expect the pattern of LH secretion to do during
the menopause in terms of both immunological and bioassayable LH? Provide
a reason for the difference between the two measures of LH in this situation.
4. What are the basic elements of a chemical communication system and
why are each of them necessary? Provide examples of each element.
5. What difference does it make if a hormone is measured by a physico-chemical
method or by a bioassay, aren't the results equivalent? If so why, if not,
why not? Include examples in your discussion whenever possible.
6. What is the importance to the whole organism of the anatomical positioning
and organization of the hypothalamus and its vascular supply to the anterior
pituitary? How would you go about proving that a hormone is produced in
the hypothalamus and acts in the pituitary rather than the other way around?
2. What is the definition of a hormone and what does that imply about
the role of bioassays in endocrinology?
3. Describe and illustrate one simple negative feedback system and one
more complex set of overlapping control systems. What would elimination
of a single hormone do to the rest of the system in each case? How might
such an elimination be useful in evaluating the function of each system?
5. What is (are) the intra- and extracellular source(s) of variability
in biological potency of protein hormones? What physiological or evolutionary
role(s) might such variability have, if any?
4. Steroids, retinoic acid and ________________ act via intracellular
receptors. In the case of the steroids all but the _______________________
appear to bind to receptors that are exclusively located in the nucleus
of the target cells. The receptors of this "super-gene" family share structural
similarities in that the receptors all have ________________ functional
domains. The closest similarities among the receptors occur in the ___________________
domain which contains a "______________-finger" motif. Some similarities
also occur in the _____________________ domain so the cross-reactivities
among some steroids for each other's receptors is not entirely surprizing.
Binding of the specific ligand by the receptor is accompanied by the release
of a ________________ ______________ ______________ that appears to function
in maintaining the receptor in an inactive state in the absence of ligand.
Reversal of the binding of the occupied receptor to the DNA hormonal recognition
element(s) for which it is specific is apparently stimulated by ____________________
of the bound hormonal ligand.
Biology 317/319 Endocrinology Exam I [Date B]
Name______________________________
Instructions: There are 100 points on this exam. The exam has
8 pages. Everyone must answer questions #1-#9. You have a choice:
answer 2 of the 5 essays, #10-#14. Budget your time and good luck.
Multiple Choice: circle all that are true/correct. 65 points, 1.5 points
for each response.
1. Hormones are always
a) proteins that have carbohydrates on their surfaces
b) specific chemical compounds that can be isolated
c) bound to serum carrier proteins
d) produced by one cell and carried via blood serum to act on another cell
e) present in serum in concentrations above 10 micromolar
f) capable of generating responses within milliseconds of binding to cell receptors
g) involved when tissues respond at the cell level
h) absolutely specific in their binding to receptors
i) unique to the species from which come, they cannot act in other species.
2. All the transduction mechanisms (hormone action mechanisms) encountered thus far directly involve ATP during the activation of cellular response except
a) the adenylate cyclase pathway
b) the tyrosine kinase mechanism
c) the nuclear ("steroid") receptor mechanism
d) the opening of membrane Na+ ion channels by acetylcholine.
3. The hypothalamus
a) lies at the base of the brain and surrounds part of the third ventricle.
b) produces both stimulatory and inhibitory peptides.
c) contains several different groupings (nuclei) of neuroendocrine cells.
d) supplies factors to the pituitary via the portal plexus.
e) does not receive inputs from the thalamus or cortex of the brain.
4. The definition of a hormone is:
a) an historical accident
b) based on interactions with antibodies
c) "something that stimulates"
d) empirical and must include description of the molecule and the effects of its absence
e) distinct from the definition of a neurotransmitter
5. Hormone receptors
a) exist in only limited numbers on target cells.
b) are always proteins.
c) are highly specific for a given hormone.
d) for multiple proteins can coexist on the membrane of the same cell.
e) remain at constant levels on single target cells at all times.
6. Changes in the levels of circulating hormones
a) closely reflect alterations in hormone receptor turnover rates.
b) occur on a time scale of seconds to hours depending on the hormone.
c) only result from gradual shifts in hormone clearance by the liver.
d) never occur without the action of a stimulating chemical agonist.
e) are only determined by the rate of hormone synthesis.
7. If a biological response to an organ extract requires seconds to minutes to occur, what group of hormones would you attempt to purify last to identify the hormone responsible?
a) amino acid derivative neurotransmitters
b) gases
c) small peptides
d) lipids
e) proteins
8. Previously uncharacterized hormone receptors might be purified from among the proteins generated in a broken-cell RNA translation experiment. They could be identified unequivocally as specific hormone receptors by:
a) their molecular size.
b) their ability to bind one specific radioactively labeled hormone in the absence, but not in the presence, of lots of the same non-radiolabeled hormone.
c) their tendency to become radiolabeled with phosphate in the presence of hormone; and ADP-O-32PO3 (-phosphate labeled ATP)
d) their tendency to be removed from solution by surfaces to which hormone agonists have covalently attached
e) their ionic charge (isoelectric point).
9. T/F Briefly, defend your answer. 15 points, 3 points each
(1 T/F, 2 defense).
T F a) Immunoassays provide the same information as bioassays.
T F b) Endocrinology as a science absolutely requires bioassays.
T F c) All endocrine stimuli result from secretions within the body.
T F d) Responses by a given target tissue to a given hormone stimulus
(same hormone and dose) are always the same.
T F e) An endocrine disease condition (endocrinopathy) can be induced
only by loss of circulating hormone.
Essay. (20 points) Choose any two of the five given.
10. Describe and illustrate one simple negative feedback system and
one positive feedback system. What would elimination of a single hormone
do to the rest of the system in each case? How might such an elimination
be useful in evaluating the function of each system?
11. In New Guinea we have found a population of humans that demonstrates
high levels of thyroxine-binding globulin (TBG) in serum in addition to
normal total thyroxine levels in serum. Another protein (SHBG) can be used
as an in vivo bioassay or "index" for free thyroxine in serum; SHBG goes
up when free thyroxine is high and SHBG goes down when free thyroxine is
low. From the above comments should we expect SHBG levels to be high or
low in our New Guineans? If we found the levels of SHBG and free thyroxine
to be normal, what could we say about the biochemical properties of TBG?
12. It has been known for some time that estrogens have a stimulatory
effect on ovarian follicular growth and oocyte maturation. Indeed, their
presence is absolutely required for ovarian gametogenesis in all animal
species thus far examined. Only recently, however, have antibodies become
available that are directed against the isolated (from chickens or cattle),
purified estrogen receptor protein. These antibodies have been used to
successfully localize estrogen receptors within the nuclei of cells in
uterine endometrium from a wide variety of species including humans and
other primates. Interestingly, however, localization experiments performed
using these same antibodies on ovarian follicular cells under a broad variety
of conditions proved negative. These cells appear in these experiments
to be devoid of estrogen receptors. Suggest at least one plausible explanation
for these findings.
13. What difference does it make if a hormone is measured by a physico-chemical
method or by a bioassay, aren't the results equivalent? If so why, if not,
why not? Include examples in your discussion whenever possible.
14. The ratio of biological potency per unit mass of FSH over immunological
reactivity per unit mass of FSH (B/I) decreases at very high and very low
FSH secretion rates because the secreted vesicles contain hormone molecules
that are either "immature" or "overmatured/aged," respectively. The B/I
ratio changes over the course of a man's lifetime. The ratio changes during
aging when the testes cease optimal function in the production of steroids
involved in negative feedback control of FSH, such as testosterone, and
of gametes. What would you expect the pattern of FSH secretion to do during
old age in terms of both immunological and bioassayable FSH? Provide a
reason for the difference between the two measures of FSH in this situation.