BRS Flashcards
1
Q
What organelle does preprohormone synthesis take place in?
A
ER
2
Q
in what organelle does a prohormone become a hormone?
A
Golgi
3
Q
Amine hormone are derivatives of what AA?
A
tyrosine
4
Q
In what two ways are hormone secretion regulated?
A
- Negative feedback
2. Positive feedback
5
Q
Hormones can regulate the sensitivity of the target tissue by regulating the _.
A
number or sensitivity of receptors.
6
Q
what is the most common method of regulating hormone secretion?
A
Negative feedback
7
Q
What is an example of a negative feedback system?
A
Insulin is secreted by the pancreatic beta cells in response to an increase in blood glucose. In turn, insulin causes an icnrease in glucose uptake into cells that results in the decreased blood glucose concentration. the decrease in blood glucose concentration then decreases further secretion of insulin
8
Q
What is an example of a positive feedback system?
A
The surge of LH that occurs just before ovulation is a result of positive feedback of estrogen on the anterior pituitary. LH then acts on the ovaries and causes more secretion of estrogen.
9
Q
What is an example of a down-regulation of receptors?
A
In the uterus, progesterone down-regulates its own receptor and the receptor for estrogen.
10
Q
How does a hormone down regulate it’s receptor?
A
by decreasing the number or affinity of receptors for itself or for another hormone.
11
Q
What is an example of up-regulation of receptors?
A
In the ovary, estrogen up-regulates its own receptors and the receptor for LH.
12
Q
Describe the series of steps in the adenylate cyclase mechanism of signaling.
A
- hormone binds to a receptor in the cell membrane.
- GDP is released from the G rpotein and replaced by GTP which activates the G protein. the G protein then activates or inhibits AC. If the G protein is stimulatory (Gs) then AC will be activated. If the G protein is inhibitory (Gi), then it will inhibit AC.
- Activated adenylate cyclase then catalyzes the conversion of the ATP to cAMP
- cAMP activates protein kinase A which phosphorylates specific protein producing highly specific physiologic action
- cAMP is degraded to 5-AMP by phosphodiesterase, which is inhibited by caffeine. therefore, phosphodiesterase inhibitors would be expected to augment the physiologic actions of cAMP.
13
Q
Describe the steps in the IP3 signaling mechanism.
A
- Hormone binds to a receptor in the cell membrane and via a G protein, activates phospholipase C
- Phospholipase C liberates diacylglycerol and IP3 from membrane lipids.
IP3 mobilizes Ca from the ER. together C and DAG activates protein kinase C which phosphorylates proteins and causes specific physiologic action.
14
Q
Describe the Ca-Calmodulin signaling mechanism.
A
- Hormone binds to a receptor in the cell membrane and via a G protein, has two actions: it opens cell membrane Ca channels and it releases Ca from the ER. Together these two actions produce an increase in intracellular Ca.
- Ca binds to calmodulin and Ca calmodulin complex produces physiologic action
15
Q
Steroid hormone and thyroid hormones acts via a similar signaling mechanism. Describe the signaling pathway.
A
- Steroid (or thyroid) hormone diffuses across the cell membrane binds to its receptor
- the hormone-receptor complex enters the nucleus and dimerizes
- the hormone-receptor dimers are transcription factors that bind to steroi-responsive elements (SREs) of DNA and initiate DNA transcription
- New messenger RNA is produced, leaves the nucleus, and is translated to synthesize new proteins
- the new proteins that are synthesized have specific physiologic actions. For example, 1,25 dihydroxycholecalciferol induces the synthesis of calbindin D-28K, a Ca binding protein in the intestine, aldosterone induce the synthesis of Na channels in the renal principal cells.
16
Q
How is the anterior lobe of the pituitary gland linked to the hypothalamus?
A
via the hypothalamic-hypothysial protal system. Hormones from the hypothamus is thus delivered directly to the anterior pituitary. Hypothalamic hormone can then stimulate or inhibit anterior pituitary hormones.
17
Q
How is the posterior lobe of the pituitary gland linked to the hypothalamus?
A
The nerve cell bodies of posterior pituitary are located in the hypothalamic nuclei. Posterior pituitary hormnes are synthesized in the nerve cell bodies packaged in secretoyr granules and transported down the axons to the posterior pituitary for release into the circulation
18
Q
List the hormones of the anterior pituitary gland.
A
- GH
- Prolectin
- TSH
- LH
- FSH
- ACTH
19
Q
Which three anterior pituitary hormones belong to the same glycoprotein family and all have an alpha and beta subunit with the alpha subunit being similar in all three but the beta is different in each and gives the hormones it’s biological activity.
A
TSH, LH, and FSH
20
Q
Which hormones are derived from the precursor POMC (pro-opiomelanocortin)?
A
ACTH, MSH, beta-lipotropins and beta-endorphins
21
Q
alpha and beta MSH are produced in which lobe of the pituitary (which is rudimentary in adult human)
A
intermediary lobe
22
Q
This peptide hormone is homologous with prolactin human placental lactogen, and is most important for normal growth to adult size
A
GH (somatotropin)
23
Q
In what conditions is GH secretion increased?
A
GH is released in pulsatile fashion and secretion is increased by sleep, stress, hormones related to puberty, starvation, exercise, and hypoglycemia.
24
Q
In what conditions is GH secretion decreased?
A
Decreased by somatostatin, somatomedin, obesity, hyperglycemia, and pregnancy.
25
Which hormone stimulates the synthesis and secretion of growth hormone?
GHRH
26
As part of the hypothalamic control, Somatostatin inhibits secretion of GH by?
By blocking the response of the anterior pituitary to GHRH.
27
As part of the negative feedback control, somatomedins are produced by_when _, and it then inhibit the secretion of GH by_.
Produced by liver. Somatomedins are produced when GH acts on target tissues and inhibits GH by 1. acting directly on the anterior pituitary and 2. by stimulating the secretion of somatostatin from the hypothalamus.
28
Besides the negative feedback by somatomedin, what else can negative feedback to control GH?
1. GHRH inhibits its own secretion from the hypothalamus.
| 2. GH also inhibits its own secretion by stimulating the secretion of somatostatin from the hypothalamus.
29
One of the action of GH is on the liver to generate the production of _ which is insulin-like growth factors (IGF), which serve as intermediaries of several physiologic actions.
Somatomedins
30
Somatomedians are insulin-like growth factor because they have similar_
Receptors which has tyrosine kinase activity.
31
GH performs its function both directly and indirectly. Directly GH does what?
1. decrease glucose uptake into cells (diabetogenic)
2. increase lipolysis
3. increase protein synthesis in muscle and increase lean body mass
4. production of IGF
32
What are the actions of GH via IGF?
1. increase protein synthesis in chondrocytes and increase linear growth (puberty growth spurt)
2. increase synthesis in muscle and increase lean body mass
3. increase protein synthesis in most organs and increase organ size
33
What are the consequence of GH deficiency in children?
1. failure to grow
2. short stature
3. mild obesity
4. delayed puberty
34
what can cause a GH deficiency?
1. Lack of anterior pituitary GH
2. Hypothalamic dysfunction thus decreased GHRH
3. Failure to generate IGF in the liver
4. GH receptor deficiency
35
Acromegaly is excess of which hormone?
GH
36
Before puberty, excess GH causes _
increased linear growth (gigantism)
37
After puberty, excess GH causes _
increased periosteal bone growth, increased organ size, and glucose intolerance
38
Which hormone is responsible for lactogenesis, particpates with estrogen in breast development, is strucurally homologous to GH
prolactin
39
What is responsible for the hypothalamic control of prolactin?
domapine, and thyrotropin-releasing hormone.
40
What action does dopamine have on prolactin secretion?
Prolactin secretion is tonically inhibited by dopamine (prolactin-inhibiting factor, PIF) secreted by the hypothalamus.
41
What happens to prolactin secretion when the hypothalamic-pituitary tract is interrupted?
Causes increased secretion of prolactin and sustained lactation.
42
What action does thyrotropin-releasing hormone have on prolactin secretion?
increases prolactin secretion
43
In the the negative feedback control of prolactin, what inhibits prolactin secretion?
Prolactin inhibits its own secretion by stimulating the hypothalamic release of dopamine.
44
What are some factors that will increase prolactin secretion?
1. estrogen (pregnancy)
2. breast-feeding
3. sleep
4. stress
5. TRH
6. dopamine antagonist?
45
What are some factors that will decrease prolactin secretion?
1. Dopamine
2. Bromocriptine (dopamine agonist)
3. Somatostain
4. prolactin ( by negative feedback)
46
What are some actions of prolactin?
1. stimulates milk production in the breast (casein, lactalbumin)
2. stimulates breast development (in a supportive role with estrogen)
3. inhibits ovulation by decreasing synthesis and release of GnRH
4. inhibits spermatogenesis ( by decreasing GnRH)
47
Prolectin deficiency can be caused by?
destruction of the anterior pituitary resulting in the failure to lactate
48
Prolactin excess can result from_.
1. hypothalamic destruction (due to loss of the tonic inhibitory control by dopamine, or
2. from prolactin-secreting tumors (prolactinomas)
49
What are some consequences of prolactin excess?
1. galactorrhea
2. failure to ovulate
3. amenorrhea because prolactin inhibits GnRH secretion
4. can
50
How can GH excess be treated?
With somatostatin analogs (e.g. octreotide)
51
How can excess prolactin be treated?
with bromocritine, which reduces prolactin secretion by acting as a dopamine agonist
52
what are the hormones of the posterior pituitary?
ADH and oxytocin
53
From which nuclei does ADH primarily originate?
from the supraoptic nuclei of the hypothalamus
54
What is the primary action of ADH?
regulates serum osmolarity by increasing the H20 permeability of the late distal tubules and collecting duct
55
What are some factors that will increase ADH secretion?
1. serum osmolarity
2. volume contraction
3. pain
4. nausea
5. hypoglycemia.
56
what are some factors that will decrease ADH secretion?
1. decrease serum osmolarity
2. ethanol
3. alpha - agonists
4. ANP
57
ADH works to increase permeability (aquaporin 2) of the principal cells of the late distal tubule and collecting duct via which receptor and which signaling pathway?
V2 receptor and AC-cAMP mechanism
58
ADH works to constrict vascular smooth muscle via which receptor and signaling pathway?
Via V1 receptor and IP3/Ca2 mechanism.
59
From which nucleus does oxytocin originate from/
Paraventricular nuclei of the hypothalamus
60
what is the action of oxytocin?
Causes ejection of milk when stimulated by suckling.
61
what is the suckling effect?
it's the stimulus for oxytocin secretin where afferent fibers carrying impulses from the nipple to the spinal cord, relays in the hypothalamaus trigger the release of oxytocin from he posterior pituitary.
62
During dilation of the cervix and orgasm, oxytocin secretion levels _.
increase.
63
which cells in the breast do oxytocin contract?
myoepithelial cells in the breast. which forces milk to be released from mammary alveoli into the ducts and delivered to the infant
64
How does oxytocin help with parturition?
During pregnancy oxytocin receptors in the uterus are up regulated as partutrition approaches, although the role of oxytocin in normal labor is uncertain. Oxytocin can be used to induce labor and reduce postpartum bleeding
65
What stimulates virtually every step of thyroid hormone synthesis?
TSH
66
In step 1 of thyroid hormone synthesis, _1_ is synthesized from _2_ in the _3_, packaged in secretory vesicles, and extruded into the follicular lumen.
1. Thyroglobulin
2. tyrosine
3. thyroid follicular cells.
67
In step 2 of thyroid hormone synthesis, what pump is used to transport I- into the thyroid follicular cells for subsequent incorporation in to the thyroid hormone?
Iodine pump, or Na-I- cotransport
68
What inhibits the Iodine pump or the Na-I cotransporter?
Thiocyanate and percholorate anions.
69
In step 3, I- is oxydized by what enzyme into I2 and what is the importance of this step?
peroxidase enzyme in the follicular cell membrane. I2 is the reactive form and will be organified by combination with tyrosine on thyroglobulin.
70
What can inhibit peroxidase and is used therapeutically to reduce thryoid hormone synthesis for the tx of hyperthyroidism.
Propylthiouracil
71
Where does organizfication of I2 take place?
follicular lumen
72
At the junction of the follicular cells and follicular lumen, tyrosine residues of thyrogolubin react with I2 to form what two intermediates.
Monoiodotryrosine (MIT) and diiodotyrosine (DIT)
73
What is the Wolff-Chaikoff effect?
High levels of I- inhibit organificatin and therefore, inhibit synthesis of thryoid hormone
74
When two molecules of DIT combine hat is formed?
Thyroxine (T4)
75
When one molecule of DIT and one molecule of MIT combine, what is formed?
triiodothyronine (T3)
76
which is synthesized more and which one is the active form, (T3, or T4)
More T4 is synthesized but T3 is the more active form.
77
where is iodinated thyroglobulin stored until the thyroid gland is stimulated to secrete thyroid hormones?
Stored in follicular lumen.
78
Describe the process that takes place when thyroid cells are stimulated by TSH.
When stimulated by tSH, iodinated thryoglobulin is taken back into the follicular cells by endocytosis. Lysosomal enzymes then digest thryglobulin, releasing T4 and T3 into the circulation.. the left over MIT and DIT are deiodinated by thryoid deiodinease. The I2 that is released is reutilized to syntehsize more thryoid hormones. Therefore deficiency of thryoid deiodinase mimics I2 deficiency.
79
T3 and T4 cannot free-float in the blood. It is bound to what?
Thyroxine-binding globulin (TBG).
80
What happens to TBG levels in hepatic failure, in pregnancy?
In hepatic failure: TBG level decrease, leading to a decrease in total thyroid hormone but normal free hormone levels.
In pregnancy, TBG levels increase leading to total thyroid hormone level but normal levels of free hormone.
81
In peripheral tissue, T4 is converted to T3 which is the more active form by what enzyme?
5'-iodinase. T3 is active. T4 can also be converted to rT3 which is the inactive form.
82
What stimulates the secretion of TSH?
TRH from hypothalamus stimulates the secretion of TSH by the anterior pituitary
83
Via what signaling pathway does TSH increase both the synthesis and secretion of thyroid hormones by the follicular cells?
Adenylate cylcase - cAMP mechanism.
84
How does T3 inhibit TSH secretion?
T3 down regulates TRH receptors in the anterior pituitary.
85
Which Ig is able to stimulate T3 and T4 release?
IgG, components of which binds to TSH reeptor and stimulates the thryoid gland to secrete T3 and T4.
86
In patients with Grave's disease, there is a (high or low) levels of thyroid hormones and accordingly theres low concentration TSH (feedback inhibition)
In graves disease there's high circulating levels of thyroid hormone
87
Attainment of adult stature requires thyroid hormone. It works synergistically with which other hormones to promote bone formation?
Growth hormone and somatomedins
88
Why is perinatal hypothyroidism screening mandatory?
Maturation of the CNS requires hormone in the perinatal period. Thyroid hormone deficiency causes irreversible mental retardation. Because there is only a brief perinatal period when thyroid hormone replacement therapy is helpful, screening is mandatory.
89
in adulthood, what does hypo and hyperthyroidism cause?
Hyperthyroidism causes hyperexcitability and irritability
| Hypothyroidism causes listlessness, slowed speech, somnolence, impaired memory, and decreased mental capacity.
90
What is the role of thyroid hormone in the autonomic NS/
Same function as sympathetic NS, because it upregulates beta-adrenergic receptors in the heart.
91
A useful adjunct therapy for hyperthryroidsim is treatment with _ because of the affect it has on the heart.
beta-adrenergic blocking agent like propranolol.
92
What effect does thyroid hormone have on basal metabolic rate?
Increases both BMR and O2 consumption, in all tissues except Brain, gonads, and spleen.
93
How does thyroid hormone regulate body temp?
thyroid hormone increases BMR and O2 consumption and this increased metabolic activity increases tamp.
94
Thyroid hormone increase the synthesis of what primary pump system and consequently increases O2 consumption related to Na-K pump activity.
Na/K ATPase
95
What effect does thyroid hormone have on heart and the lungs?
heart: Increase HR and SV = increase CO
lungs: increase ventilation rate
96
What metabolic effects does thyroid hormone have?
1. overal metabolism is icnreased to meet the demand for substrate associated with increased rate of O2 consumption
2. glucose absorption from the GI is increase
3. Glycogenolysis, gluconeogenesis, and glucose oxidation are all increased
4. lipolysis increased
d. protein synthesis and degradation are increased.
overball effect of thyroid hormone is catabolic.
97
What are some symptoms associated with hyperthyroidism?
1. increased metabolic rate
2. weight loss
3. negative nitrogen balance
4. increased heat production (sweating)
5. increased CO
6. Dyspnea
7. tremor, weakness
8. exopthlmos
9. Goiter
98
What are some symptoms associated with hypothyroidism?
1. decreased metabolic rate,
2. weight gain
3. positive nitrogen balance
4. decreased heat production (cold sensitivity)
5. decreased CO
6. hypoventilation
7. Lethary, mental slowness,
8. drooping eyelids
9. myxedema
10. growth and mental retardation (perinatal)
11. Goiter
99
What are some causes of hyperthyroidism?
1. Graves disease (antibodies to TSH receptor)
| 2. Thyroid neoplasm
100
What are some causes of hypothyroidism?
1. thyroiditis (autoimmune thryroidisi; Hashimoto's thryoidisiti)
2. surgical removal of thyroid
3. I- deficiency
4. Cretinism (congenital)
5. decreased TRH or TSH
101
How can hypothyroidism be treated?
Thryoid hormone replacement
102
How can hyperthyroidism be treated?
Propylthiourocil
Thryoidectomy
131-I
beta-blockers *adjunct therapy
103
Where is aldosterone produced?
Zona glomerulosa in the adrenal cortex
104
Where is glucocorticoids produced?
In the zona fasciculata in the adrenal cortex
105
The zona reticularis produces mostly which hormones?
dehyroepiandrosterone and androstenedione)
106
The 21-carbon steroids include_
progesterone (precursor for the others listed here), deoxycorticosterone, aldosterone, and cortisol
107
Hydroxylation at C21 leads to production of _ which has mineralocortioid activity but not glucocorticoid activity
deoxycorticosterone
108
Hydroxylation at C-17 leads to production of _
glucocorticoids (cortisol).
109
19-C steroids produces which type of hormones?
Produces androgen (has androgenic activity) and are precursor to the estrogens.
110
If the steroid has been previously hydroxylated C 17, the C20,21 side chain can be cleaved to yield which 19-Carbon steroids?
dehyroepiandrosteone and androstenedione int he adrenal cortex.
111
In the testes, androstenedione is converted to what hormone?
testosterone
112
19 carbon steroids have androgenic activity, whereas 18-carbon steroid have _
estrogenic activity
113
Oxidation of the A ring (aromatization to produce estrogens occurs where?
In ovaries and placenta (NOT in the adrenalc cortex or testes)
114
one of the function of glucocorticoids is to regulate circadian. For who who sleep at night, cortisol levels are _ just before waking in the morning and _ in the evening around midnight.
Highest in the morning
| lowest at night.
115
in hypothalamic control - corticotropin-releasing hormones are located where?
paraventricular nuclei of the hypothalamus.
116
Describe the hypothalamic control of glucocorticoid secretion.
CRH-containing neurons in the paraventricular nuclei and when stimulated, CRH is released into hypothalamic-hypophysial protal blood and delivered to the anterior pituitary. CRH binds to receptors on corticotrophs of the anterior pituitary and directs them to synthesize POMC (the precursor to ACTH) and secrete ACTH.
117
What second messenger does CRH use?
cAMP
118
ACTH increases steroid synthesis in which zone of the adrenal cortex?
in all zones.
119
ACTH stimulates what hormone and thus increases the conversion of cholesterol to pregnenolone
Cholesterol demsolase
120
What second messenger does ACTH use?
cAMP
121
Chronic increasing levels of ACTH will cause hypertrophy of what?
adrenal cortex.
122
In negative feedback control, cortisol can be inhibited by what?
Cortisol inhibits the secretion of CRH from the hypothalamus and secretion of ACTH from the anterior pituitary.
123
Dexamethosone suppression test is used in what situations and what does it test?
Dexamethosone is a synthetic glucocorticoid to inhibit ACTH secretion. In normal person, low dose dexamethasone inhibits or supresses ACTH and consequently cortisol secretion. It is used to test for either ACTH secreting tumors or adrenal cortical tumors.
124
Patients with ACTH-secreting tumors, what dose (high or low) is needed to get a positive dexamethosone suppression test?
High dose.
125
In patients with adrenal cortical tumors, what dose of dexamethasone is needed to get a positive test?
Neither. these tumors do not respond to dexamethasone.
126
Ang II acts on which zone of the adrenal cortex?
Zona glomerulosa to increase the conversion of corticosterone to aldosterone
127
What effect does hyperkalemia have on aldosterone secretion?
increases
128
Overall, glucocorticoids are essential in the response to stress. What role does cortisol play during stress on a) gluconeogenesis, b) Inflammation, C) Immune response, and d) vascular response to cetecholamines
A. Increase gluconeogenesis
B. induce the synthesis of lipocrotin and inhibitor of phospholipase A and together have anti-infammatory effects
C. Supression of immune response by inhibiting production of IL2 and T lymphocytes -- prevent rejection of transplanted organs
D. Maintains vascular responsiveness to catecholamines by up regulating a1 receptors on arterioles.
129
By what mechanism do cortisol increase gluconeogenesis?
1. increase protein catabolism in muscle and decrease protein synthesis, --> provide more aa for gluconeogenesis
2. decrease glucose tulization and insulin sensitivity of adipose tissue
3. increase lipolysis which provides more glycerol to the liver for gluconeogenesis
130
What are three ways cortisol have anti-inflammatory effects.
1. induce the synthesis of lipocortin and inhibit phospholipase A which thus inhibits formatin of the precursor arachidonate which is needed for production of prostaglandin and leukotriene.
2. inhibit production of IL-2 and inhibit proliferation of T lymphocytes
3. inhibit the release of histamine and serotonin from mast cells and platelets
131
What would happen to arterial blood pressure with cortisol deficiency?
arterial blood pressure decreases. opposite happens with cortisol excess.
132
What is addison's disease?
primary adrenocortical insufficiency where adrenal glands do not produce sufficient steroid hormones like cortisol and aldosterone. Most commonly caused by autoimmune adrenalitis causing destruction of the adrenal cortex and causes acute adrenal crisis.
133
what are some clinical features of addison's disease?
- hypoglycemia
- anorexia, weight loss, nausea, vomitting
- weakness
- hypotension
- hyperkalemia
- metabolic acidosis
- decreased pubic and axillary hair in women
- hyperpigmentation (low cortisol levels stimulate ACTH secretion; ACTH contains the MSH fragment)
134
Would you see increased or decreased level of ACTH with addison's disease?
Increased cuz the negative feedback is decreased.
135
What is Cushing's syndrome and is it caused by?
It's a primary adrenal hyperplasia caused by both external and internal causes. External could be due to taking too much as prescribed to treat some other disease. In endogenous causes it can be due to benign pituitary adenoma, adrenal gland tumors, or tumors in other places that which effects the adrenal glands.
136
what are some clinical signs of Cushing's syndrome?
- hyperglyceia
- muscle wasting
- central obesity
- round face, supraclavicular fat, buffalo hump
- osteoporosis
- striae
- viriluzation and menstrual disorders
- hypertension
137
What is Cushion's disease?
Excess ACTH
138
In Cushings syndrome would you see increased or decerased ACTH?
decreased. cuz the negative feedback o increased cortisol.
139
What is Conn's syndrome?
aldosterone secreting tumor common cause of which is due to enlargement of both adrenal glands
140
What are some clinical signs of Conn's syndrome?
hypertension,
- hypokalemia
- metabolic alkalosis
- decreased renin
141
What does 21-beta-hydroxylase deficiency lead to?
leads to decreased glucocorticoids and mineralocorticoids; and increased adrenal androgens. It is the most common biochem abnormality of the steroidogenic pathway.
142
What are some clinical signs of 21-beta-hydroxylase deficiency?
-virilization of woman
-early acceleration of linear growth
-early appearance of pubic and axillary hair
symptoms of glucocorticoid and minerlocorticoid dificiency
143
what does 17alpha-hydroxylase deficiency lead to?
decreased adrenal androgens and glucocorticoids (cuz the enzyme block prevents the production of 17-hydroxypregnnenolone and 17-hyrroxyprogesterone); increased mineralocorticoids (cuz intermediates accumulate to the left of the block and are shunted towards the production of mineralocorticoids
144
what are some clinical signs of 17alpha-hydroxylase deficiency?
- lack of pubic and axillary hair in woman
- symptoms of glucocorticoid deficiency
- symptoms of mineralocorticoid excess
145
With 17a-hydrolase deficiency would you expect ACTH to be elevated or decreased? with about 21beta hydroxylase deficiency?
increased in both.
146
How does secondary adrenocrotical insufficiency present?
It's caused by primary deficiency of ACTH. So you do not get hyperpigmentaiton, and no not exhibit volume contraction, hyperkalemia, or metabolic acidosis ( cuz aldosterone levels are normal). Symptoms are otherwise similar to those of Addison's disease.
147
with 21-beta hyroxylase deficiency, which precursors are not formed and thus cortisol and aldosterone levels are low.
11-deoxycortisol, and 11-deoxycorticosterone
148
why do you see increased androgens with 21beta-hydoryxlase deficiency?
Because of accumulation of intermediates above the enzyme block leading to increased 17hyroxyprogesterone
149
In 21-beta-hydroxylase theres hyperplasia of zona fasciulata and zona reticularis, why?
Due to high levels of ACTH.
150
The beta cells, alpha cells, are linked to each other via _ for rapid communication
gap junctions
151
Via what second messenger does glucagon work?
cAMP
152
how does glucagon increase blood glucose?
1. increase glycogenolysis and prevents the recycling of glucose into glycogen
2. it increases gluconeognesis which increases 2.6 bisphosphate deceasing phosphofructokinase activity; in effect, substrate is directed toward glucose formation rather than toward glucose breakdown.
153
what are the main actions of glucagon?
1. increase blood glucose concentraiton
2. increase blood fatty acid and ketoacid concentration by increasing lipolysis.
3. increase urea production
154
Explain how insulin is synthesized.
Insulin contains an A and a B chain, joined by two disulfide bridges. Proinsulin is synthesized as a single-chain peptide. within storage granules, a connecting peptide (C peptide) is removed by proteases to yield insulin. The C peptide is packaged and secreted along with insulin and its concentration is used to monitor beta cell function in diabetic patients who are receiving exogenous insulin.
155
what are some factors that increase glucagon secretion?
- decreased blood glucose
- increased amino acid (especially arginine)
- CCK (alerts alpha cells to a protein meal)
- ACh
156
What are some factors that decrease glucagon secretion?
- increased blood glucose
- insulin
- somatostatin
- fatty acids, ketoacids
157
what are some factors that increase insulin secretion?
- increased blood glucose
- increased amino acids (arg, lys, leu)
- increased fatty acids
- glucagon
- GIP
- Ach
158
what are some factors that decrease insulin secretion?
- decreased blood glucose
- somatostatin
- NE or E
159
Explain the mechanism of insulin secretion.
- Glucose, the stimulant for insulin secretion, binds to glut2 receptor on the beta cells.
- inside the beta cells, glucose is oxidized to ATP, which closes K channels in the cell membrane and leads to depolarization of the beta cells. similar to the action of ATP, sulfonylurea drugs (e.g. tolbutamine, glyburide) stimulate insulin secretion by closing these K channels
- depolarization opens Ca channels, which leads to an increase in intracellular Ca and then to secretion of insulin.
160
The insulin receptor a tetramer composed of _
2 alpha and 2 beta subunits
161
which of the insulin receptor subunits have tyrosine kinase activity?
the beta subunits.
162
What causes the autophosphorylation of beta subunits of insulin receptors?
When insulin binds to the receptor it autophosphorylates the beta subunits. the phosphorylated receptor then phosphorylates intracellular proteins.
163
The number of insulin receptors is increased in _ and decreased in _
increased in starvation. decreased in obesity
164
what are the general actions of insulin?
1. decrease blood glucose concentration
2. decrease blood fatty acid and ketoacid concentration
3. decrease blood amino acid concentration
4. decrease blood K concentration
165
via which mechanisms do insulin decrease blood glucose concentration?
1. increase uptake of glucose into target cells by directing the insertion of glucose transporters into the cell membrane. As glucose enters the cells, the blood glucose concentration decrease.
2. Promote formation of glycogen form glucose in muscle and liver, and simultaneously inhibits glycogenolysis.
3. it decreases gluconeogenesis. Insulin increases the production of fructose 2,6bis phosphate, increasing phosphofructokinase activity. in effect, substrate is directed away from glucose formation
166
How does insulin decrase blood fatty acid and ketoacid concentration?
In adipose tissue, insulin stimulates fat deposition and inhibits lipolysis. It also inhibits ketoacid formation in the lvier becuase fatty acid degradation provides less acetyl CoA substrate for keotacid formation
167
Overall, insulin is anabolic or catabolic?
anabolic.
168
```
A woman shows up to the ED with hypotension and tachypnea, breath has the odor of ketones. Analysis of her blood shows severe hyperglycemia, hyperkalmeia, and blood gas values are consistant with metabolic acidosis. What is the explanation for a. hyperglycemia
b. hypotension
c. metabolic acidosis,
d. hyperkalmeia.
What is the likely diagnosis?
```
A. hyperglycemia due to insulin deficiency thus glucose cannot be taken into cells or stored as glycogen.
B. Hypotension - due to ECF volume contraction. The high blood glucose concentration results in a high filtered load of glucose that exceeds the reabsrptive capacity (Tm) of the kidney. The unreabsorbed glucose acts as an osmotic diuretic in the urine and causes ECF volume contraction.
C. Metabolic acidosis, caused by overproduction of ketoacids
D. hyperkalemia due to lack of insulin which normally promotes K uptake into cells.
Diagnosis: diabetes mellitus.
169
Secretion of insulin, glucagon, and gastrin can be inhibited by which pancreatic hormone?
Somatostatin
170
what is the source of Ca and phosphate to ECF for bone mineralization?
Vitamin D
171
What does vitamin D deficiency cause in children? in adults?
rickets in children. Osteomalacia in adults.
172
What is the active form of vitamin D?
1,25 dihydroxycholecalciferol.
173
what production of 1,25 dihyroxycholecalciferol in the kidney is catalyzed by what enzyme?
1a-hydroxylase
174
what factors increases 1a-hydroxylase activity?
1. decreased serum Ca
2. Increased PTH levels
3. decreased serum phosphate
175
1,25 dihyroxycholecalciferol is is coordinated to increase _1_ and _2_, in ECF to do what?
1. [Ca2+]
2. [Phosphate]
To mineralize new bone.
176
In what ways does 1,25 dihydroxycholecalciferol increase Ca and phosphate concentration in ECF?
1. increases intestinal Ca absorption.
2. increase intesinal phosphate absorption
3. increase renal reabsorption of ca and phosphate
4. increase bone resorption which provides Ca and phosphate from old bone to mineralize new bone
177
What is calbindin D-28K?
It is a Ca binding protein which is induced by 1,25-dihyroxycholecalciferol.
178
how does PTH increase intestinal Ca absorption?
It does it indirectly by stimulating 1a-hydroxylase and increasing production of the active form of vitamin D.
179
Where is calcitonin syntehsized and secreted from?
parafollicular cells of the thyroid
180
What simulates the secretion of calcitonin?
increase in serum Ca
181
What is the primary function of calcitonin?
it acts to inhibit bone resorption
182
```
A 41-year-old woman has hypocalcemia, hyperphosphatemia, and decreased urinary phosphate excretion. Injection of parathy- roid hormone (PTH) causes an increase in urinary cyclic adenosine monophosphate (cAMP). The most likely diagnosis is
(A) primary hyperparathyroidism
(B) vitamin D intoxication
(C) vitamin D deficiency
(D) hypoparathyroidism after thyroid
surgery
(E) pseudohypoparathyroidism
```
D
183
Which of the following hormones acts on its target tissues by a steroid hormone mechanism of action?
(A) Thyroid hormone
(B) Parathyroid hormone (PTH)
(C) Antidiuretic hormone (ADH) on the col-
lecting duct
(D) β1 adrenergic agonists
(E) Glucagon
A
184
A 38-year-old man who has galactorrhea is found to have a prolactinoma. His physician treats him with bromocriptine, which eliminates the galactorrhea. The basis for the therapeutic action of bromocriptine is that it
(A) antagonizes the action of prolactin on the breast
(B) enhances the action of prolactin on the breast
(C) inhibits prolactin release from the ante- rior pituitary
(D) inhibits prolactin release from the hypothalamus
(E) enhances the action of dopamine on the anterior pituitary
C.
185
```
Which of the following hormones originates in the anterior pituitary?
(A) Dopamine
(B) Growth hormone–releasing hormone
(GHRH)
(C) Somatostatin
(D) Gonadotropin-releasing hormone
(GnRH)
(E) Thyroid-stimulating hormone ( TSH)
(F) Oxytocin
(G) Testosterone
```
E.
186
Which of the following functions of the Sertoli cells mediates negative feedback control of follicle-stimulating hormone (FSH) secretion?
(A) Synthesis of inhibin
(B) Synthesis of testosterone
(C) Aromatization of testosterone
(D) Maintenance of the blood–testes barrier
A
187
```
Which of the following substances is derived from pro-opiomelanocortin (POMC)?
(A) Adrenocorticotropic hormone (ACTH)
(B) Follicle-stimulating hormone (FSH)
(C) Melatonin
(D) Cortisol
(E) Dehydroepiandrosterone
```
A.
188
```
Which of the following inhibits the secretion of growth hormone by the anterior pituitary?
(A) Sleep
(B) Stress
C. puberty
D. stomatomedins
E. Starvation
F. Hypoglycemia.
```
D.
189
Selective destruction of the zona glomerulosa of the adrenal cortex would produce a deficiency of which hormone?
(A) Aldosterone
(B) Androstenedione
(C) Cortisol
(D) Dehydroepiandrosterone (E) Testosterone
A.
190
Which of the following explains the sup- pression of lactation during pregnancy?
(A) Blood prolactin levels are too low for milk production to occur
(B) Human placental lactogen levels are too low for milk production to occur
(C) The fetal adrenal gland does not pro- duce sufficient estriol
(D) Blood levels of estrogen and proges- terone are high
(E) The maternal anterior pituitary is sup- pressed
D.
191
Which step in steroid hormone biosynthesis, if inhibited, blocks the production of all androgenic compounds but does not block the production of glucocorticoids?
(A) Cholesterol → pregnenolone
(B) Progesterone → 11-deoxycorticosterone
(C) 17-Hydroxypregnenolone → dehy-
droepiandrosterone
(D) Testosterone → estradiol
(E) Testosterone → dihydrotestosterone
C
192
```
A 46-year-old woman has hirsutism, hyperglycemia, obesity, muscle wasting, and increased circulating levels of adrenocorti- cotropic hormone (ACTH). The most likely cause of her symptoms is
(A) primary adrenocortical insufficiency (Addison’s disease)
(B) pheochromocytoma
(C) primary overproduction of ACTH
(Cushing’s disease)
(D) treatment with exogenous glucocorti-
coids
(E) hypophysectomy
```
C
193
```
Which of the following decreases the conversion of 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol?
(A) A diet low in Ca2+
(B) Hypocalcemia
(C) Hyperparathyroidism
(D) Hypophosphatemia
(E) Chronic renal failure
```
E.
194
Increased adrenocorticotropic hormone (ACTH) secretion would be expected in patients
(A) with chronic adrenocortical insufficien- cy (Addison’s disease)
(B) with primary adrenocortical hyperplasia
(C) who are receiving glucocorticoid for
immunosuppression after a renal trans-
plant
(D) with elevated levels of angiotensin II
A.
195
Which of the following would be expected in a patient with Graves’ disease?
(A) Cold sensitivity
(B) Weight gain
(C) Decreased O2 consumption
(D) Decreased cardiac output
(E) Drooping eyelids
(F) Atrophy of the thyroid gland
(G) Increased thyroid-stimulating hormone
(TSH) levels
(H) Increased triiodothyronine (T3) levels
H
196
```
Blood levels of which of the following substances is decreased in Graves’ disease?
(A) Triiodothyronine (T3)
(B) Thyroxine (T4)
(C) Diiodotyrosine (DIT)
(D) Thyroid-stimulating hormone (TSH)
(E) Iodide (I–)
```
D
197
```
Which of the following hormones acts by an inositol 1,4,5-triphosphate (IP3)–Ca2+ mechanism of action?
(A) 1,25-Dihydroxycholecalciferol
(B) Progesterone
(C) Insulin
(D) Parathyroid hormone (PTH)
(E) Gonadotropin-releasing hormone
(GnRH)
```
E
198
Which step in steroid hormone biosynthesis is stimulated by adrenocorticotropic hormone (ACTH)?
(A) Cholesterol → pregnenolone
(B) Progesterone → 11-deoxycorticosterone
(C) 17-Hydroxypregnenolone → dehy-droepiandrosterone
(D) Testosterone → estradiol
(E) Testosterone → dihydrotestosterone
A
199
```
Which of the following causes increased aldosterone secretion?
(A) Decreased blood volume
(B) Administration of an inhibitor of
angiotensin-converting enzyme (ACE)
(C) Hyperosmolarity
(D) Hypokalemia
```
A.
200
```
Secretion of oxytocin is increased by
(A) milk ejection
(B) dilation of the cervix
(C) increased prolactin levels
(D) increased extracellular fluid (ECF) volume
(E) increased serum osmolarity
```
B
201
```
Propylthiouracil can be used to reduce the synthesis of thyroid hormones in hyper- thyroidism because it inhibits oxidation of
(A) Triiodothyronine (T3)
(B) Thyroxine (T4)
(C) Diiodotyrosine (DIT)
(D) Thyroid-stimulating hormone (TSH)
(E) Iodide (I–)
```
E.
202
```
A 39-year-old man with untreated diabetes mellitus type I is brought to the emergency room. An injection of insulin would be expected to cause an increase in his
(A) urine glucose concentration
(B) blood glucose concentration
(C) blood K+ concentration
(D) blood pH
(E) breathing rate
```
D
203
Which of the following results from the action of parathyroid hormone (PTH) on the renal tubule?
(A) inhibition of 1a-hydroxylase
B. stimulation of Ca2+ reabsorption in the distal tubule
C Stimulation of phosphate reabsorption in the proximal tubule
D. interaction with receptors on the luminal membrane of the proximal tubular cells
D. decreased urinary excretion of cAMP
B
204
Which step in steroid hormone biosynthesis occurs in the accessory sex target tissues of the male and is catalyzed by 5α-reductase?
(A) Cholesterol → pregnenolone
(B) Progesterone → 11-deoxycorticosterone
(C) 17-Hydroxypregnenolone → dehy-
droepiandrosterone
(D) Testosterone → estradiol
(E) Testosterone → dihydrotestosterone
E.
205
```
Which of the following pancreatic secretions has a receptor with four subunits, two of which have tyrosine kinase activity?
(A) Insulin
(B) Glucagon
(C) Somatostatin
(D) Pancreatic lipase
```
A
