Physiology - Endocrine / Reproductive Block Flashcards
(295 cards)
1
Q
Describe some of the classifications of hormones based on their starting point and mode of travel.
A
2
Q
Endocrine cells typically release peptide hormones in response to increased intracellular concentrations of what substance?
Does this increase or decrease protein phosphorylation and microtubule action?
A
[cAMP] + [Ca2+]
(and the associated fusion of vesicles with the cell membrane);
increase
3
Q
Peptide hormone -coding mRNA is translated on the ER to ____________ and then processed via signal peptide cleavage in the ER to ____________.
What happens next?
A
Preprohormones,
prohormones;
post-translational modifications (e.g. phosphorylation, glycosylation) in the Golgi
4
Q
Where are preprohormones synthesized from mRNA?
Where are prohormones then produced? How?
What happens next?
A
ER,
signal peptide cleavage;
post-translational modifications and processing in the Golgi
5
Q
Thyroid hormones are synthesized from what precursors?
Steroid hormones are synthesized from what precursors?
A
Tyrosine + iodide;
cholesterol
6
Q
In which glands are steroid hormones stored?
A
They are not stored in any appreciable quantity.
7
Q
Which is more common, genetic causes of peptide hormone disorders or steroid hormone disorders?
A
Steroid hormone disorders
(usually defects in the enzyme pathyway from cholesterol to the specific hormone)
8
Q
How do most genetic steroid hormone disorders occur?
How do most genetic peptide hormone disorders occur?
A
Mutations in the enzymes in the synthetic pathways;
mutations in the hormones themselves
9
Q
__________ hormones are released from cells via exocytosis.
A
Peptide
10
Q
What cytoskeletal structures in particular are necessary for peptide hormone secretion (via exocytosis)?
A
Microtubules,
microfilaments
11
Q
An increase in what cellular content(s) will cause exocytosis of peptide hormones from endocrine organs?
A
cAMP,
Ca2+
12
Q
Peptide hormones are released from endocrine organs directly into:
A
The interstitial space
13
Q
How does an increase in intracellular Ca2+ and cAMP cause increased peptide secretion from endocrine cells?
A
Increased protein phosphorylation and microtubule activation
(Ca2+ also activates myosin light-chain kinase, promoting granule movement)
14
Q
Describe how intracellular Ca2+ increases peptide hormone exocytosis in endocrine tissues via its interactions with MLCK.
A
15
Q
True/False.
Both negative and positive feedback systems are involved in virtually all levels of endocrine cell functions.
A
True
(i.e. transcription, translation, secretion)
16
Q
At steady state, what is a hormone’s metabolic clearance rate?
A
The mass of hormone removed per unit time
/
plasma concentration of the hormone
17
Q
What is the equation for metabolic clearance rate?
A
18
Q
What organs are the main locations of hormone degradation?
A
Liver;
kidneys
19
Q
True/False.
Virtually all peptide hormone degradation is via proteolysis.
A
False.
Example processes include: proteolysis, oxidation, reduction, hydroxylation, decarboxylation, methylation, etc.
20
Q
In hormone kinetics, what are meant by H, R, and HR?
A
H - free hormone
R - free receptor
HR - hormone-bound receptor
21
Q
At equilibrium (in hormone kinetics), KAssoc =
A
KAssoc = [HR] / [H][R]
(also = 1 / Kdissoc)
22
Q
In hormone kinetics, what is represented by R0?
A
Initial receptor capacity
(R + HR)
23
Q
What is a Scatchard plot?
What shape does it display?
A
A graph representing the ratio of bound hormone to free hormone;
theoretically, a straight line —
— in practice, an exponential curve
24
Q
The slope of the line in a Scatchard plot is:
The intercept of the line in a Scatchard plot is:
A
- KAssociation
(i. e. Kd)
R0 (receptor number)
25
**True/False**.
A small amount of membrane receptors can often yield the maximum response offered by a peptide hormonal system.
True.
(Limits are in place as to how high the maximal effect can be.)
26
Which is limited in effect by receptor number? (I.e. more receptors = more effect)
Which is fully activated at a low receptor occupancy? (I.e. more hormone won't make a difference)
Steroid hormones;
peptide hormones
27
Which has spare receptors that aren't being used, peptide or steroid hormones?
Which is limited by the number of spare receptors that are available for use, peptide or steroid hormones?
**Peptide** (fully activated system at low hormone-receptor occupancy);
**steroid** (more receptors = more effect)
28
List some of the major intracellular secondary messengers induced by hormonal action.
cAMP
cGMP
Ca2+
IP3
diacylglycerol
29
What might occur if a tissue is chronically overstimulated by hormone input?
Downregulation of receptors
| (desensitization)
30
What intracellular secondary messenger is increased by ANP binding?
cGMP
| (via guanylyl cyclase)
31
What intracellular secondary messenger is increased by nitric oxide binding?
cGMP
| (via guanylyl cyclase)
32
What GPCR increases intracellular cGMP?
What does cGMP then activate?
Guanylyl cyclase;
cGMP-dependent protein kinase
33
What are the two main ways in which hormone response curves can change?
How does the curve change in either option?
Changes in:
**sensitivity** (left- or right-shift)
or
**maximal responsiveness** (shifts Vmax up or down)
34
What two tests are very sensitive for amounts of hormone?
What is the drawback to these tests?
Radioimmunoassays, ELISA;
both measure antigenic amount of hormone, not necessarily biologically active hormone
35
Are radioimmunoassay and ELISA testing more likely to underestimate or overestimate biologically active hormone concentrations?
Overestimate
## Footnote
*(because it measures non-active with active)*
36
What is the specific drawback of radioimmunoassays in measuring hormone levels?
What test avoids this drawback with no loss in sensitivity?
Radiation;
ELISA
37
What are the three portions of the adenohypophysis?
Describe where they are.
Pars distalis
Pars tuberalis
Pars intermedia
38
What are the three portions of the neurohypophysis?
Median eminence
Infundibulum
Pars nervosa
39
What three portions of the hypothalamus release corticotropic hormones?
The paraventricular nucleus,
medial preoptic nucleus,
and arcuate nucleus
40
What two portions of the hypothalamus send hormones to the neurohypophysis?
The paraventricular nucleus,
the supraoptic nucleus
41
What is found within the median eminence of the pituitary?
The neurovascular region connecting the hypothalamus to the adenohypophysis
42
What type of circulation connects the adenohypophysis to the median eminence?
A portal system
## Footnote
*(capillary bed draining into capillary bed)*
43
Describe the hypothalamic-hypophyseal portal system.
44
List the hormonal release triggered by each of the following:
**GnRH**
**TRH**
**CRH**
**GHRH**
**GnRH**: LH, FSH;
**TRH**: TSH, prolactin;
**CRH**: ACTH;
**GHRH**: GH
45
List the corticotropic hormone that causes the release of each of the following:
## Footnote
**LH**
**GH**
**Prolactin**
**TSH**
**ACTH**
**FSH**
**LH**: GnRH
**GH**: GHRH
**Prolactin**: TRH
**TSH**: TRH
**ACTH**: CRH
**FSH**: GnRH
46
Release of what hormone(s) of the anterior pituitary is inhibited by somatostatin?
GH;
TSH
47
Release of what hormone(s) of the anterior pituitary is inhibited by dopamine?
Prolactin
(dopamine also known as prolactin-inhibiting factor)
48
What are the five cell types of the adenohypophysis (in order of decreasing quantity)?
Somatotrophs
Mammotrophs
Corticotrophs
Gonadotrophs
Thyrotrophs
49
Cellular differentiation in the anterior pituitary is mediated by what transcription factor?
Pit-1
50
**True/False**.
Anterior pituitary secretion is near-continuous to meet the body's continous basal metabolic needs.
**False**.
Anterior pituitary secretion is pulsatile.
51
The pituitary gland sits within what bony structure of the _________ bone?
Sella turcica;
sphenoid
52
**True/False**.
The anterior pituitary is derived from the fetal neuroectoderm.
**False**.
The anterior pituitary is derived from the fetal foregut.
53
What cell type of the adenohypophysis secretes LH and FSH?
Gonadotrophs
54
What cell type of the adenohypophysis secretes thyrotropin (TSH)?
Thyrotrophs
55
What cell type of the adenohypophysis secretes growth hormone and somatotropin?
Somatotrophs
56
What cell type of the adenohypophysis secretes prolactin?
Mammotrophs
57
What cell type of the adenohypophysis secretes adrenocorticotropin (ACTH)?
Corticotrophs
58
What type of cell in the adenohypophysis is most abundant? What proportion does it make up?
What three types of cell are next most abundant?
What type of cell in the adenohypophysis is least abundant?
**Somatotrophs** (50%)
**gonadotrophs, corticotrophs, mammotrophs** (15% each)
**thyrotrophs** (5%)
59
What substances stimulate ACTH secretion from the adenohypophysis?
What are a few positive modulators for this process?
CRH, ADH;
norepinephrine, acetylcholine, and 5-HT
60
What substances inhibit ACTH secretion from the adenohypophysis?
What are a few negative modulators for ACTH release?
Cortisol, brain natriuretic peptide;
ACTH, endorphins, GABA
61
Cortisol inhibits which portions of the hypothalamic-pituitary axis?
CRH and ACTH release
62
What disease is characterized by primary adrenal insufficiency?
Addison's disease
63
CRH and ACTH both increase intracellular levels of what enzyme (leading to all other downstream effects)?
PKA
64
Growth hormone shares homology with what other pituitary hormone?
Prolactin
65
**True/False**.
Most of the cells of the adenohypophysis secrete some level of GH.
True.
66
Pulsatile ______ increases GH release from the adenohypophysis.
Pulsatile ______ decreases GH release from the adenohypophysis.
\_\_\_\_\_\_ also decreases GH release from the adenohypophysis.
**GHRH**;
**somatostatin**;
**IGF-1** (increases somatostatin release)
67
What is the main effect of growth hormone?
Stimulation of postnatal growth
68
Prolactin release from the adenohypophysis is mostly _stimulated_ by what substance?
Prolactin release from the adenohypophysis is mostly _inhibited_ by what substance?
**TRH**;
**dopamine** (PIF)
69
Which adenohypophyseal hormones are all members of the glycoprotein hormone family?
FSH, LH, TSH, β-HCG
70
TSH, LH, FSH, and β-HCG are each made of ___ subunits.
Which gives the specificity?
2;
β
71
Which hormone produced by the follicular cells of the thyroid inhibits TRH and TSH release?
T3
72
**True/False**.
FSH and LH decrease after menopause.
**False**.
They increase.
73
Name the precusor to ACTH.
What else does this precursor become?
Proopiomelanocortin;
β-endorphins, α-melanocyte-stimulating hormone
74
How many pulses of GnRH per hour are required to maintain baseline levels of both LH and FSH?
1 per hour
75
Less frequent GnRH pulses (1 per 3 hours) stimulates what?
More frequent GnRH pulses stimulates what?
FSH secretion;
LH secretion
76
What substance selectively inihibits FSH secretion?
Inhibin
77
LH secretion is mediated by _______ GnRH pulses.
FSH secretion is mediated by _______ GnRH pulses.
Fast;
slow
78
Name the respective tropic hormone responsible for increasing release of each of the following:
Prolactin
LH
TSH
GH
FSH
ACTH
TRH
GnRH
TRH
GHRH
GnRH
CRH
79
Name the respective adenohypophyseal hormones released by stimulation from the following tropic hormones:
TRH
GnRH
GHRH
CRH
TSH, prolactin
FSH, LH
GH
ACTH
80
What transport protein(s) carry oxytocin and ADH from the hypothalamus to the neurohypophysis?
Neurophysin I (oxytocin)
neurophysin II (ADH)
81
ADH and oxytocin secretion is mainly mediated via:
Neuronal input
82
Is transport from the hypothalamus to the neurohypophysis slow or fast transport?
Fast
| (mm / hour)
83
**True/False**.
The paraventricular nucleus produces only oxytocin and the supraoptic nucleus produces only ADH.
**False**.
The paraventricular nucleus produces *mainly* oxytocin and the supraoptic nucleus produces *mainly* ADH, but both produce a small quantity of the alternate hormone.
84
**True/False**.
Both the paraventricular and supraoptic nuclei each produce _both_ ADH and oxytocin.
**True**.
| (at least in small amounts)
85
ADH and oxytocin are released from what portion of the neurohypophysis?
The pars nervosa
86
What are pituicytes?
Glial cells of the neurohypophysis
87
Are the axons found in the pars nervosa of the neurohypophysis myelinated or unmyelinated?
Unmyelinated
88
What are the main functions of ADH?
Increased renal H2O reabsorption;
systemic vasoconstriction (at pharmacological doses)
89
What are the main functions of oxytocin?
Uterine contraction;
mammary gland myoepithelial contraction;
bonding
90
ADH and oxytocin are both ___ amino acids in length.
They only differ in ___ amino acid residues.
9;
2
91
The similarity in structure between ADH and oxytocin means what?
They may have overlapping effects
92
What are some examples of the types of injury can disrupt the neuronal tracts that transport ADH and oxytocin?
Is regeneration of these axons possible?
Trauma, tumor, surgery;
yes
93
ADH binds what two receptors?
| (What does each do?)
**V1** (vasoconstriction)
**V2** (vasodilation; renal H2O reabsorption)
94
What renal effects does ADH cause via the V2 receptor?
1) Reabsorption of NaCl via stimulation of **Na/K/2Cl** co-transport in the thick ascendening limb
2) Increase the permeability of the collecting duct to **urea**
3) Increase permeability of the collecting ducts to **H2O**
95
What effect does ADH have on cortisol levels?
ADH stimulates release of ACTH
96
The supraoptic nucleus mainly secretes:
The paraventricular nucleus mainly secretes:
ADH
oxytocin
97
What is the main stimulus for ADH secretion?
What are two others?
Increased plasma osmolarity
hypovolemia, increased CSF [Na+]
*(also, nausea, angiotensin II, temperature increase, nicotene, histamine, bradykinin)*
98
What is the main inhibitory stimulus preventing ADH secretion?
What are two others?
Decreased plasma osmolarity
normo- or hypervolemia, decreased CSF [Na+]
*(also, EtOH, ANP, temperature decrease, norepinephrine)*
99
What effect does EtOH ingestion have on ADH secretion?
Inhibition
100
What are the primary S/Sy of diabetes insipidus?
What are some others?
**Polyuria** (5-15 L/day), **polydipsia**;
hypernatremia, increased serum osmolality (290 - 295 mOsm/Kg), muscle weakness, fever, hypoosmotic urine
101
What are the main electrolyte and osmolality changes seen in diabetes insipidus?
Hypernatremia;
increased serum osmolality (290 - 295 mOsm/Kg)
102
What are the two types of diabetes insipidus?
Central;
nephrogenic
103
A patient presents with a 2-week history of polyuria and polydipsia. You suspect diabetes insipidus. This needs to be differentiated from what other potential causes?
Diabetes mellitus,
psychogenic polydipsia/polyuria
104
What are some potential causes of central diabetes inspidus?
**Destruction of hypothalamic nuclei**
(tumors, trauma, surgery);
**inherited**
(neurophysin mutation)
105
What are some potential causes of nephrogenic diabetes insipidus?
**Chronic** **kidney** **disease**,
ADH receptor or aquaporin2 **deficiency**,
**drugs** (lithium)
106
What test results can be used to diagnose _central_ diabetes insipidus?
**Water deprivation test** (urine osmolality will not increase);
**desmopressin test** (urine osmolality will increase)
107
What is the main therapy for central diabetes insipidus?
**Desmopressin**
| (vasopressin analog)
108
What are the S/Sy of syndrome of inappropriate antidiuretic hormone secretion (SIADH)?
**Most patients have no signs** (no peripheral edema, no signs of dehydration);
hyponatremia below 110 mmol/l --\> weakness, lethargy (leading to coma)
109
What are some potential causes of syndrome of inappropriate antidiuretic hormone secretion (SIADH)?
**Para-neoplastic syndromes** (lungs, pancreas, lymphoma);
**non-neoplastic lung disease** (COPD, pneumonia, TB);
**brain disorders** (tumors, encephalitis, meningitis, hemorrhage);
**certain drugs** (antidepressants, diuretics, narcotics)
110
Describe the expected lab results in a patient with SIADH.
Hypervolemia,
low Serum osmolality (\<270 mOsm/kg),
hyponatremia (\<130 mmol/l),
hypertonic urine (\>300 mOsm/kg),
increased urine [Na+] (\>20mmol/l)
111
What are the main treatment options for SIADH?
Water restriction;
medications to block V2 receptors
112
On routine labwork in an asymptomatic patient, you notice that they are hyponatremic and their urine is hypertonic. What do you suspect?
SIADH
113
Oxytocin causes contraction of smooth muscle in what two locations in particular?
Breast myoepithelial cells;
the uterus
114
What clinical uses does pitocin (oxytocin) have in the peripartum period?
To induce labor;
to stop uterine bleeding after labor
115
The actions of oxytocin are augmented by what endogenous substance and blocked by what other endogenous substance?
Estrogen;
catecholamines
116
Which is involved in the let-down reflex in breastfeeding, oxytocin or prolactin?
Oxytocin
117
Is milk ejection during breastfeeding by positive or negative pressure or both?
(I.e. does the breast use positive pressure to eject the milk or does the infant create negative pressure and draw it out?)
Positive pressure
(myoepithelial cell contraction in response to suckling)
118
**True/False**.
Milk ejection from the breast is psychogenic.
True.
119
After the completion of childhood and puberty, what effect/role does GH still have?
Modulating metabolism
120
**True/False**.
Patients with acromegaly or those being treated with GH are at an increased risk of tumor development (and cardiovascular hemorrhage at higher doses).
True.
121
Is GH a steroid or peptide or other type of hormone?
Peptide
122
What organ secretes IGF-1?
What effect does this substance have on the adenohypophysis?
The liver;
inhibit GH release (along with somatostatin)
*(IGF-1 is also known as somatomedin)*
123
What stimuli increase GHRH secretion?
What stimuli decrease GHRH secretion?
Sleep, stress, fasting;
glucose, free fatty acids, GHRH
124
GHRH increases what intracellular secondary messengers in somatotrophs?
Ca2+, cAMP, IP3
125
**True/False**.
Thyroid hormones, cortisol, estrogen, and testosterone all synergistically decrease GH synthesis and release.
**False**.
Thyroid hormones, cortisol, estrogen, and testosterone all synergistically *_increase_* GH synthesis and release.
126
What two factors increase somatostatin release from the adenohypophysis?
GH;
somatomedin (IGF-1)
127
What generic growth types are increased by GH action?
Linear growth,
organ size,
lean body mass
128
What effect does GH have on IGF-1 secretion by the liver?
An increase
129
**True/False**.
An amino acid-rich meal increases GH release.
True.
130
**True/False**.
GH levels are higher in children and adolescents than adults.
**True**.
| (Peak during puberty)
131
Name some of the effects of GH on adipose tissue, muscle, and the liver.
132
Name some of the diverse effects of GH and IGFs on tissues besides the liver, muscle, and adipose tissues.
133
Is somatostatin a steroid or peptide hormone?
Peptide
134
What effect does somatostatin have on GHRH-secreting cells of the hypothalamus?
Decreased intracellular cAMP and Ca2+;
decreased frequency/amplitude of GHRH pulses
135
What is the main stimulating substance for GH release?
What is the main inhibiting substance for GH release?
GHRH;
somatostatin
136
What effect does obesity have on GH levels?
A **reduction in GH responses to all stimuli**, including GHRH
137
Name a few stressors that can increase GH release.
Exercise, trauma, surgery, anesthesia, fever
138
**True/False**.
A morning surge in GH occurs at 1-2 hours after waking.
**False**.
A nocturnal surge in GH occurs at 1-2 hours after the onset of deep sleep.
139
What are two signs of a childhood GH deficiency?
Short stature, moderate obesity
140
**True/False**.
All of the following are effects of administration of GH to GH-deficient children:
Enhance positive nitrogen balance
Decrease urea production
Redistribute fats
Reduce carbohydrate utilization
(does not increase the incidence of diabetes mellitus)
True.
141
What effect does GH replacement for GH-deficient children have on adiposity?
Decreased
142
GH activates what receptor type?
**JAK-STAT** tyrosine kinases
143
Insulin-like growth factors (a class of peptide hormone) are also known as what?
Somatomedins
144
GH promotes the synthesis of what two substances in many tissues?
Where do most protein-bound, circulating IGFs originate?
**IGF-1**, **IGF-2**;
the liver
145
**True/False**.
IGFs inhibit tissue growth.
**False**.
IGFs mediate the process of growth.
146
GH stimulates the transformation of ____________ into chondrocytes, which then start secreting \_\_\_\_\_.
Prechondrocytes,
IGF-1
147
How does GH influence longitudinal bone growth?
It increases chondrocyte maturation;
the chondrocytes secrete IGF-1;
stimulates clonal expansion in endochondral growth plates
148
Administration of IGFs to GH-deficient children or adults decreases plasma amino acid levels due to enhanced \_\_\_\_\_\_\_\_\_\_\_\_\_\_.
Protein synthesis
149
What effect do GH and IGF have on body composition?
Lean body mass increases,
fat mass decreases,
bone formation is enhanced
150
What effect do GH and IGF have on body metabolism and function?
Increased:
BMR, exercise capacity, sense of well-being
151
GH and IGF increase the secretion of what two ECM substances in particular?
Collagen, chondroitin sulfate
152
GH stimulates synthesis of what substances in almost all cell types?
DNA, RNA, protein
153
**True/False**.
GH and insulin work synergistically.
**False**.
GH increases insulin expression but opposes insulin action.
154
GH decreases glucose uptake by what tissue types?
GH increases catabolism of what macronutrient type?
Muscle, adipose;
lipids
155
What effect does GH have on adipose tissue and free fatty acids?
Free fatty acids (and ketones) increase;
adipose tissue decreases
156
GH can be considered a \_\_\_\_\_\_\_\_genic hormone.
Diabeto-
157
While GH and insulin have many opposing effects, what effect do they share?
_Increased IGF production_, leading to **increased lean body mass**
158
What vital role does GH play in opposing insulin?
Preventing hypoglycemia
159
If [GH] is high and [insulin] is low, what will IGF be?
Low
| (requires both)
160
**True/False**.
Acromegaly diagnosis can be delayed 15 - 20 years until onset of clinically noticable S/Sy.
True.
161
**True/False**.
Prolactin is glycosylated in the Golgi and then deglycosylated in the ER.
**False**.
Prolactin is glycosylated in the _ER_ and then deglycosylated in the _Golgi_.
162
Besides dopamine, what other two factors inhibits prolactin secretion?
Somatostatin,
GnRH
163
**True/False**.
Prolactin secretion is only possible when the hypothalamus is closely connected to the adenohypophysis.
**False**.
Disruption of pituitary connections to the hypothalamus leads to a *great increase in prolactin secretion*
164
What effect does prolactin have on hypothalamic function?
It inhibits GnRH secretion
165
A 46 year old African-American male presents himself to a primary care physician for evaluation of sudden weight loss. He complains of palpitations and racing heart beats. He always feels warm and nervous with shaky hands. He is irritable, fatigued, apprehensive, and unable to concentrate.
## Footnote
**Make the diagnosis.**
Hyperthyroidism
166
Describe the general histology of thyroid follicles.
Cuboidal, single-layered circular follicles;
the follicular lumen contains colloid material (hormone storage)
167
What is the main hormone secreted from the thyroid?
What is secreted in smaller quantities?
Tetraiodothyronine (T4);
triiodothyronine (T3)
168
Which thyroid hormone is biologically active?
T3
169
What are the two main substrates for thyroid hormone synthesis?
Tyrosine + iodide
170
What are the main steps of thyroid hormone synthesis?
1. Uptake / concentration of iodide
2. Oxidation of tyrosine residues with iodide
3. Coupling of two iodinated tyrosine residues
171
Where does thyroid hormone synthesis occur?
The thyroid follicles
172
The tyrosine residues to be iodinated in thyroid hormone synthesis are held as links of what peptide?
Thyroglobulin
173
What enzyme iodinates thyroglobulin during thyroid hormone synthesis?
Thyroid peroxidase
174
After thyroglobulin is iodinated in thyroid follicles, what occurs next?
Proteolytic cleavage of thyroid hormones from thyroglobulin
175
Where is the majority of T3 produced?
Target tissues
(converted from T4)
176
Via what mechanism is iodide transported into follicular cells of the thyroid?
Na+-cotransport
| (secondary active)
177
What is the chemical formula for iodide?
I-
178
Na+-I- cotransport (secondary active transport) into thyroid follicular cells is known as:
Iodide trap
179
**True/False**.
The iodide trap (sodium-iodide cotransport into thyroid follicular cells) leaves a larger concentration of iodide in the plasma than the follicular cells.
**False**.
The iodide trap (sodium-iodide cotransport into thyroid follicular cells) leaves a **much** larger concentration of iodide *_in the follicular cells than in the plasma_*.
180
What two tyrosine residues are produced from thyroid peroxidase activity acting on thyroglobulin?
Monoiodotyrosine;
diiodotyrosine
181
What enzyme found in the thyroid contains heme?
Thyroid peroxidase
182
One molecule of T3 is made from a molecule of ____________ being coupled to a molecule of \_\_\_\_\_\_\_\_\_\_\_\_.
One molecule of T4 is made from a molecule of ____________ being coupled to a molecule of \_\_\_\_\_\_\_\_\_\_\_\_.
Diiodotyrosine + monoiodotyrosine;
diiodotyrosine + diiodotyrosine
183
What is the ratio of T4 to T3 in the thyroid?
10:1
184
Where are iodinated thyroglobulin stored?
The thyroid colloid
185
How do iodinated thyroglobulin leave the thyroid follicular lumen?
Via what receptor?
Endocytosis;
megalin
186
Once iodinated thyroglobulin is reabsorbed into thyroid follicular cells from the thyroid colloid, what happens next?
Lysosomal enzymes release T4 and T3 from thyroglobulin
## Footnote
*(T4 and T3 are then released from the cells into the capillary blood)*
187
What happens to unused monoiodotyrosine and diiodotyrosine in the thyroid?
Deiodinase removes the iodide for reuse
188
What type of drug blocks thyroid peroxidase?
Thiouracils
189
What type of drug is used to treat hyperthyroidism?
Via what mechanism?
Thiouracils;
inhibition of thyroid peroxidase
190
**True/False**.
Iodine can be used to treat hyperthyroidism.
**True**.
(Both as radioactive iodine and to inhibit T3 and T4 release.)
191
Describe how iodide is absorbed / thyroid hormones formed / thyroid hormones secreted in thyroid follicular cells.
192
Describe if each of the following occur within the thyroid follicular cell or at the interface of the apical membrane and colloid:
## Footnote
**Iodide Trap**
**Thyroglobulin Synthesis**
**Iodination**
**Coupling**
**Proteolytic Cleavage**
Iodide Trap - **Intracellular**
Thyroglobulin Synthesis - **Intracellular**
Iodination - **Colloid**
Coupling - **Colloid**
Proteolytic Cleavage - **Intracellular**
*(See image for clarification.)*
193
**True/False**.
Iodide is coupled to free tyrosine residues in the colloid to form monoiodotyrosine and diiodotyrosine.
**True/False**.
Iodide is coupled to _thyroglobulin tyrosine residues_ in the colloid to form monoiodotyrosine and diiodotyrosine.
194
Thyroglobulin tyrosine + one iodide atom =
Thyroglobulin tyrosine + two iodide atoms =
Thyroglobulin tyrosine + one iodide atom = **Monoiodotyrosine**
Thyroglobulin tyrosine + two iodide atoms = **Diiodotyrosine**
195
What two products can result from one monoiodotyrosine molecule being coupled with one diiodotyrosine molecule in the thyroid colloid?
T3;
reverse T3
196
The TRH gene codes for the amino acid sequence *glutamine-histidine-proline-glycine*. How is this peptide turned into TRH?
Removal of the glycine
| (TRH = glutamine-histidine-proline)
197
**True/False**.
Plasma TRH desensitizes / down-regulates its receptor to diminish its effectiveness on thyrotrophs.
True.
198
Which actions of the thyroid follicular cells are controlled by TSH?
Virtually all of them
## Footnote
***i.** Iodide trapping*
***ii.** T4 and T3 synthesis*
***iii.** Colloidal endocytosis*
***iv.** Proteolytic release of T4 and T3 from the gland.*
***iv.** Metabolism and growth of thyroid cells*
199
An iodine deficiency or defect in thyroid hormone production lead to what effect as a result of chronically elevated TSH levels?
**Goiter**
*(TSH stimulates follicular cell growth and replication as well as hormone production)*
200
Why does hypothyroidisim result in increased thyroid size (goiter) if thyroid function is decreased?
Elevated TSH --\>
stimulates follicular cell growth and replication as well as hormone production
201
**True/False**.
Primary hypothyroidism can lead to a diminished size adenohypophysis even as it leads to an enlarged thyroid (goiter).
**False**.
Primary hypothyroidism can lead to an _enlarged adenohypophysis (increased number of thyrotrophs)_ as it leads to an enlarged thyroid (goiter).
202
Besides thyroid hormones, what are some other substances that decrease TSH release from the adenohypophysis thyrotrophs?
Dopamine, somatostatin, cortisol, growth hormone
203
**True/False**.
T3 and T4 circulate freely in the bloodstream.
**False**.
They circulate bound to _thyroxine-binding globulin (TBG) (20%), albumin, and transthyretin_.
204
T3 and T4 circulate in the bloodstream bound to what substances?
Thyroxine-binding globulin (TBG) (20%),
albumin,
transthyretin
205
How does the body buffer against acute changes in thyroid function?
**Excess T4** **circulates as a reservoir** bound to thyroxine-binding globulin and transthyretin
206
Free T4 / Bound T4 =
Free T4 / Bound T4 = **1 / KEq [TBG]**
207
**True/False**.
About 3% of total T4 and T3 are in the free state and available for use.
**False**.
About **0.03%** of T4 and **0.3%** of T3 are in the free state and available for use.
208
What are some examples of disorders that can affect thyroid function by changing [thyroxine-binding globulin]?
Acute hepatic disease;
pregnancies, estrogen therapy;
kidney disease
209
T4 has only \_\_\_% of the hormonally activity of T3.
What enzyme converts T4 to T3?
25%
5-monodeiodinase
210
What are the three _major_ target tissues of thyroid hormone?
Liver,
kidney,
skeletal muscle
211
Does cellular uptake of T3 and T4 require energy expenditure?
Where in the cell do these hormones exert their effects?
Yes;
the nucleus (affecting gene expression)
212
Describe the effects of thyroid hormone on metabolism.
213
Describe the effects that increased thyroid hormone has on each of the following:
## Footnote
**Thermogenesis**
**Sweating**
**Blood flow**
**BMR**
**Ventilation**
**O2 consumption**
Increased
Increased
Increased
Increased
Increased
Increased
214
Thyroid hormone is especially important in the fetal development of what two organ systems?
Brain,
bone
215
What effect does thyroid hormone have on cardiac activity?
Increased cardiac stroke volume, heart rate, systolic blood pressure;
decreased diastolic blood pressure
216
What is the main mechanism by which thyroid hormone increases mitochondrial O2 consumption?
Increased Na+/K+ ATPases
217
What is the effect of thyroid hormone on the kidneys?
Increased kidney size, renal plasma flow (RPF), glomerular filtration rate (GFR), and transport in kidney tubules
218
**True/False**.
Thyroid hormone increases catabolism of vitamins, steroid hormones, and many drugs.
True.
219
What are the general S/Sy of hyperthyroidism?
Elevated heart rate,
sweating,
heat intolerance,
thirst,
increased thirst,
muscle weakness,
osteoporosis
220
List a few causes of hyperthyroidism.
**1.** Grave's disease (autoantibodies stimulate TSH receptors)
**2.** Benign thyroid neoplasm
**3.** Thyroid inflammation
**4.** Ingestion of thyroid hormone or excess iodide
**5.** Elevated TSH
221
List a few treatments for hyperthyroidism.
**Surgery**,
β-blockers,
short-term iodine excess,
thiouracils,
radioactive iodine
222
Describe some general S/Sy of hypothyroidism seen in either adults or children.
Cold intolerance,
decreased sweating,
dry skin,
low cardiac output,
weight gain
223
Describe the clinical S/Sy of cretinism.
Mental retardation, delayed body development;
lethargy, growth retardation, and poor performance
224
What is the most common cause of goiterous hypothyroidism?
Hashimoto's thyroiditis
225
What antibody is the main cause of Hashimoto's thyroiditis?
Anti- (thyroid peroxidase) antibodies
226
**True/False**.
Mutations in thyroid hormone signal transduction can result in clinical hypothyroidism.
True.
227
From external to internal, what are the three layers of the adrenal cortex?
\*Which is largest?
Zona glomerulosa
Zona fasciculata\*
Zona reticularis
228
What is the main product of the zona glomerulosa?
What is the main product of the zona fasciculata?
What is the main product of the zona reticularis?
**Aldosterone** (mineralocorticoids)
**Cortisol** (glucocorticoids)
**DHEA** (androgens)
229
**True/False**.
Fetal adrenal glands are very functional, and the glands grows rapidly after birth.
**False**.
Fetal adrenal glands are _very large, and the glands reduce_ in size rapidly after birth.
230
The functional cells of the adrenal medulla are known as what?
Pheochromocytes (chromaffin cells)
231
How much of the adrenal gland is made up by the cortex?
What is the epinephrine-to-norepinephrine ratio secreted by the medulla?
80%
80:20
232
Where are steroid hormones stored in the adrenal glands?
They are not
233
What substance(s) increase(s) zona glomerulosa secretions?
What substance(s) increase(s) zona fasciculata secretions?
What substance(s) increase(s) zona reticularis secretions?
**Angiotensin II** (to a small degree, ACTH);
**ACTH**;
**ACTH**
234
What three substances are necessary to cytochrome P450 function in steroid hormone synthesis from cholesterol?
**O2**;
**NADPH**;
**adrenoxin** (iron-containing protein)
235
What is the most common cause of excessive secretion of cortisol and adrenal androgens?
**ACTH hypersecretion** by the adenohypophysis
236
The _direct_ precursor to aldosterone is:
The _direct_ precursor to cortisol is:
18-OH corticosterone;
11-deoxycortisol
237
Which cholesterol carbons must be hydroxylated in creating cortisol?
C-17, C-21, and C-11
238
Synthesis of aldosterone requires addition of an _______ group in case of the C-\_\_ methyl group/
Aldehyde;
18
239
Upon being released from the adrenal zona reticularis, what happens to the androgen precursors (e.g. DHEA)?
Peripheral conversion to testosterone or estradiol
240
What are three precursor androgens released by the adrenal zona reticularis?
Androstenedione
DHEA
DHEA-S
241
Adrenal androgen precursors supply a larger proportion of the androgenic demand in which sex?
Females
(most male androgens come from the testes)
242
**True/False**.
ADH has a strong stimulatory effect on ACTH secretion.
**False**.
ADH has a _weak_ stimulatory effect on ACTH secretion.
243
What effect does cortisol have on either the hypothalamus or adenohypophysis?
Inhibition of both CRH and ACTH secretion
244
\_\_\_\_\_\_\_\_\_\_\_\_-induced analgesia inhibits cortisol release.
Endorphins
245
**True/False**.
Cortisol directly stimulates many processes such as glycogenolysis.
**False**.
Cortisol is _a *permissive* hormone_ and enhances these processes when stimulated.
246
What is the main purpose of cortisol in the stress response?
Gluconeogensis
| (increased plasma glucose)
247
What are three tissue types upon which excessive cortisol has deleterious effects?
Bones, skin and muscle
248
What hormone of the adrenal cortex decreases bodily insulin sensitivity?
Cortisol
| (a diabetogenic hormone)
249
**True/False**.
Cortisol stimulates protein conversion to glucose AND glucose conversion to hepatic glycogen.
True.
250
Cortisol permits maximum growth hormone and epinephrine stimulation of \_\_\_\_\_\_\_\_\_\_.
Lipolysis
251
What effect does cortisol have on adipose distribution?
**Central** adiposity increases
252
Name the effect of cortisol on each of the following tissues' growth/function:
## Footnote
**Skeletal muscle**
**Cardiac function**
**Arteriolar tone**
**Bone**
**Connective tissue**
**Fetal maturation**
**GFR**
Decrease
Maintain
Increase
Decrease
Decrease
Increase
Increase
253
What are a few examples of conditions that might indicate an individual should not be administered glucocorticoids?
Infections, diabetes, osteoporosis
254
What are the clinical S/Sy of Cushing's syndrome?
Thin skin, easy brusing (capillary weakness);
muscle weakness, osteoporosis, fatigue;
central obesity
255
What are the two main effects of aldosterone?
Maintaining **ECF volume**;
maintaining normal plasma **[K+]**
256
ANP and BNP inhibit \_\_\_\_\_\_\_\_\_\_\_'s effects on the nephron tubules.
Aldosterone
257
What effect does dopamine have on aldosterone?
Decreased synthesis / secretion
258
What are the main categories of the S/Sy seen in Addison's disease?
**Hypoaldosteronism**: natriuresis, hypotension
**Hypocortisolism**: weakness, stress intolerance, weight loss
**Androgen** **loss**: anemia, loss of body hair
259
What percentage of pancreatic islet cells are β cells?
And α cells?
And δ cells?
70%
20%
10%
260
What do pancreatic β cells secrete?
And α cells?
And δ cells?
And PP cells?
Insulin;
glucagon;
somatostatin, gastrin;
pancreatic polypeptide
261
**True/False**.
Insulin promotes a catabolic state, and glucagon promotes an anabolic state.
**False**.
Insulin promotes _an anabolic state_, and glucagon promotes _a catabolic state_.
262
Describe insulin's structure.
An **A peptide chain** (21 amino acids) and a **B peptide chain** (30 amino acids) connected by **2 disulfide bonds**
263
Describe the synthesis and modification of insulin from its gene.
Gene --\> mRNA --\>
preproinsulin --\> proinsulin + N-terminus --\>
insulin + C-peptide
264
Describe the structure of proinsulin.
The A and B chains connected by C-peptide in addition to their disulfide bonds.
265
What happens to proinsulin after C-peptide is cleaved off and it becomes insulin?
It is packaged in storage granules until release
266
What transporter allows uptake of glucose into pancreatic β cells?
What happens next?
**GLUT2**;
## Footnote
*they enter glycolysis --\> [ATP] increases --\> KATP channels close --\> cell depolarization --\> insulin release*
267
Influx of ___ allows for exocytosis of ___ from pancreatic β cells.
Ca2+;
insulin
268
When graphed, the relationship between plasma glucose and plasma insulin is _________ (shape of the curve).
Sigmoidal
269
Virtually no insulin is secreted below a plasma glucose threshold of ≈ ___ mg/dl.
A half-maximal insulin secretory response occurs at a plasma glucose level of ≈ ___ mg/dl.
Maximal insulin response occurs at a level of ≈ ___ mg/dl.
50
150
300
270
Describe the insulin response to continous glucose stimulus.
**Biphasic**:
pulse peaking at 1 min.
---
long-term pulse starting at 10 min. and peaking over several hours
271
Fasting and prolonged exercise _________ plasma insulin levels.
Obesity markedly _________ insulin secretion.
Sustained physical conditioning _________ insulin secretion.
Decrease;
increases
decreases
272
**True/False**.
Insulin secretion is stimulated by all of the following: certain amino acids (arginine and lysine), free fatty acids, triglycerides, potassium, calcium, and vitamin D.
True.
273
Early type II diabetes mellitus is characterized by a complete loss of recognition of ________ as a stimulus for ________ secretion.
Glucose;
insulin
274
Insulin circulates bound to what protein?
How long is insulin's half-life?
None;
5 - 8 minutes
275
An increase in intracellular ____ and ____ are the usual secondary messengers for hormone release from peripheral endocrine tissues.
Ca2+; cAMP
276
What feedback process regulates oxytocin secretion during childbirth?
**Positive** feedback
(uterine contraction / cervical stretching --\> increased oxytocin secretion until the baby is ejected and the cervical stretching stops)
277
Are the overall effects of GH anabolic or catabolic?
Anabolic
278
When are GH levels highest?
Adolescence
| (decreases with age)
279
GH acts through which specific receptor-associated tyrosine kinase system?
JAK-STAT
280
Describe the effects of GH on each of the following (increased/decreased):
## Footnote
**Lean body mass**
**Fat mass**
**Blood sugar**
**Protein synthesis**
**Lipolysis**
**Resting BMR**
Increased
Decreased
Increased
Increased
Increased
Increased
281
Name a few diabetogenic hormones that have antagonistic effects towards insulin (typically via phosphorylation of intracellular insulin receptor substrates).
Glucagon,
epinephrine,
growth hormone,
cortisol
282
What hormone is mainly anabolic but also acts to increase lipolysis and blood glucose?
Growth hormone
283
Via what action does aldosterone synthase convert corticosterone to aldosterone?
**Oxidation** of the **C18** methyl group
284
Describe the insulin-mediated mechanism of GLUT4 expression on skeletal muscle and adipose cells.
Insulin --\> extracellular alpha receptor --\> intracellular beta subunit --\> tyrosine kinase activity on insulin receptor substrate 1 --\> **PI3 kinase activity** --\> GLUT4 brought to membrane
285
**True/False**.
Insulin up-regulates insulin receptors.
**False**.
Insulin downregulates insulin receptors.
286
How do many diabetogenic hormones (cortisol, epinephrine, GH, glucagon) act to down-regulate insulin's effects?
**Phosphorylation of insulin receptor substrate 1 (IRS1)**
(inhibited GLUT4 membrane fusion --\> increased insulin --\> insulin receptor down-regulation)
287
**True/False**.
Glucagon inhibits insulin release.
**False**.
Glucagon *stimulates* insulin release.
288
What is the ratio of insulin:glucagon when fasting?
What is the ratio of insulin:glucagon for a few hours after eating?
1: 2
2: 1
289
**True/False**.
Insulin stimulates glucagon secretion.
**False**.
Insulin *inhibits* glucagon secretion.
290
If blood sugar is above __ mM, a person is said to be **_hyper_**glycemic.
If blood sugar is below __ mM, a person is said to be **_hypo_**glycemic.
6.7;
2
291
Pancreatic polypeptide inhibits what?
Exocrine secretion
292
Elevated pancreatic polypeptide is indicative of what?
An islet cell tumor
293
What pancreatic cell type secretes gastrin?
Islet G cells
294
What hormones are produced by pancreatic islet cells?
**Insulin** (+C-peptide),
**glucagon**,
**somatostatin**,
**gastrin**,
**pancreatic polypeptide**,
**VIP** (non-beta islet cells)
295
What are the two important substrates activated by insulin receptors?
IRS1,
PI3 kinase
