Fall Test 1.1 Flashcards
1
Q
Three chemical classes of hormones
A
Peptide
Steroid
Amine
2
Q
Which of the three types of hormones have something in common with the other ones
A
Peptide and NE, E, and DA are hydrophilic and polar like peptide hormones
Catecholamines (amines) can act as NTM’s like peptide hormones
Steroid and amines are small
Cortisol (cortex) and NE and E (medulla) are made in the kidneys
3
Q
What are the precursors for the three classes of hormones
A
Peptide - preprohormone (AA’s and foldings)
Steroid - cholesterol
Amine - tyrosine
4
Q
General pathway for steroid synthesis
A
Peptide hormone
G protein coupled receptor activated
Adenyl cyclase activated
Increase cAMP
PKA activated
Cholesterol esterases stimulated
Cholesterol released from intracellular stores
StAR transports cytoplasmic cholesterol to mitochondria
Cholesterol is converted to steroids by P450 enzymes
5
Q
General pathway for peptide hormone synthesis
A
- Preprohormone (AA/foldings)
- Prohormone (in vesicles)
- Hormone (after 2nd cleavage)
6
Q
How are hydrophilic hormones stored, and where?
Lipophilic hormones
A
Secretory vesicles in Golgi apparatus
7
Q
Cellular location of receptors for peptide hormones and catecholamines?
How is this different than that of steroid and thyroid hormone receptor
A
P/C: hydrophilic receptors are on cell surface/in plasma membrane
S/T: intracellular/nuclear receptors
8
Q
Three general types of inputs that control hormone secretion by an endocrine cell, and example of each
A
- Plasma concentrations of nutrient
- GH and glucose, Ca regulating hormone
- Neural Control
- Psychological stress responses
- Hormonal control
- GnRH -> LH - > T
9
Q
Tropic hormone:
A
Hormone that has another endocrine gland as its target. Most are made by ant. Pit
10
Q
Large polar or hydrophilic hormones are transported how
Lipophilic hormones require what
A
In the blood dissolved in plasma
Carrier proteins
11
Q
How are small, nonpolar or lipophilic hormones transported in the blood
A
Bound to binding/carrier proteins
12
Q
Organs most important for metabolism or hormones, how?
A
Liver/kidneys
Have enzymes that break down hormones by hydrolysis or sulfation
13
Q
Organs most important for excretion of hormones
A
Liver/kidney
14
Q
Other mechanisms by which some hormones are removed from the blood or inactivated,
depends on what
A
Circulating enzymes degrade some,
depends on molecular size and association with binding proteins
15
Q
How do binding proteins decrease the rate at which bound hormones are cleared from the blood
A
Steroid and thyroid hormones are less susceptible to degradation because they attach to binding proteins.
16
Q
Anatomical relationship b/t hypothalamus and pituitary
A
Pituitary is just below in the sella turcica
Infundibulum connects hypothalamus to post. Pit
17
Q
Importance of pituitary portal vasculature
A
It’s how the hypothalamus talks to the anterior pituitary
18
Q
Anterior pituitary vs. posterior pituitary
Tissues developed from
Nature of connections to the hypothalamus
A
Ant: from outpocketing of oral ectoderm
Connected to hypothalamus by portal veins
Post: buds off from floor of hypothalamus
Connected by hypothalamus
19
Q
Two posterior pituitary hormones
Site of synthesis
Mechanism of release
Actions on target tissues
A
Oxytocin/vasopressin
Made in supraoptic and paraventricular nuclei
Oxytocin stimulates smooth muscle contraction
Vasopressin regulates BP in kidney and blood vessels
20
Q
6 hormones secreted by anterior pituitary
Which hypophysiotropic or hypothalamic hormones control their release
Target tissues?
Effect of hormone on target tissue?
A
GnRH -> FSH -> Gonads
GnRH -> LH -> Gonads ( Germ cell/hormones)
Somatostatin -> GH -> Liver/other (protein synth., secrete IGF-1)
TRH -> TSH -> Thyroid (thyroid hormones)
Dopamine blocks -> Prolactin -> Breasts (milk)
CRH -> ACTH -> Adrenal Cortex (secretes cortisol)
21
Q
Inputs that control secretion of hypophysiotropic hormones from hypothalamus
A
Controlled by neural signals (stimulatory/inhibitory)
Controlled by other hormones via feedback mechanisms (long loop and short loop)
22
Q
Negative vs. positive feedback mechanisms in endocrine system
A
Positive finish responses
Negative return hormone conc’s to normal
23
Q
Long loop negative feedback vs.
Short loop negative feedback
A
Long loop is self-regulation by product/hormone of ULTIMATE target tissue
E.g. cortisol/ACTH
Short-loop is when hormone from 2nd gland in axis affects the action of the 1st gland
E.g. LH/GnRH
24
Q
Thyroid hormones are made from _ and are a _ hormone
A
Iodination of tyrosine
Amine hormone
25
How is cholesterol stored
It isn’t, but pieces are stored In LDL's, stored in lipid droplets due to low water solubility
26
Location of thyroid gland?
Inf. To larynx, across trachea
27
Importance of thyroid follicles and colloid in function of the gland
Follicle cells regulate production of two iodine containing thyroid hormones
Thyroid hormone is synthesized extracellularly in colloid, can be stored in colloid
28
Organs and hormones of thyroid axis
Hypothalamus - TRH
Anterior pituitary - TSH
Thyroid - thyroid hormones
29
T3 vs. T4
More common in circulation?
Functionally most important
T4 more common
| T3 functionally most important
30
Major steps in synthesis of thyroid hormones
1. Iodide across basal side of follicle cells via Na/I transporter
2. Iodide diffuses down conc gradient across apical membrane into colloid of follicle
3. Follicle cells synthesis TG and thyroid peroxidase. Both exocytose across apical membrane into colloid
4. Iodide is oxidized by Thy. Per. In colloid (ECF) and linked to TG. (1 is MIT, 2 is DIT) This maintains conc. Gradient needed to continuously sequester I in colloid
5. DIT + DIT = T4, DIT + MIT = T3. T3/T4 remain attached to TG, stored in Colloid.
31
Importance of iodine and thyroglobulin in the synthetic process
TG binds I to maintain conc gradient so more I will diffuse down conc gradient
32
Where do the steps of synthesis of thyroid hormones take place (intra/extracellularly)
Synthesized extracellularly in colloid. Can be stored in colloid.
33
Once synthesized, thyroid hormone is stored to bound thyroglobulin in follicular colloid.
Why is this storage mechanism necessary to regulate the release of the hormone?
How does it facilitate continued uptake of iodide into the colloid?
It maintains conc. Gradient of I so that I can move down its conc gradient into colloid to facilitate more TH production
34
Major steps in secretion of thyroid hormone
How secretion is stimulated
What are the processes involved in getting thyroid hormone from the colloid into the blood?
1. TSH causes TG + T3/T4 to be pinocytosed into follicle cells
2. Droplet fuses with lysosome with enzymes to cleave TG from T3/T4
3. T3/T4 released in cytoplasm by lysosomal hydrolysis
4. T3/T4 diffuse into capillaries. TG AAs are recycled to new TG
35
T/F most of the hormone secreted is T3 but most T4 is converted to the more physiologically important T3 form of hormone
FALSE
Most secreted is T4
Most T4 IS converted to more important T3
36
TSH also stimulates _
Thyroid hormone exerts _ on secretion of TRH and TSH
Follicle cell metabolism and replication
Negative feedback effects
37
Which cells, and where in the cells is the location of the thyroid hormone receptor? Cellular response to activation?
TH receptors are in the nuclei of most cells of the body.
TH -> Receptor -> dimerize, form DNA binding protein that regulates gene transcription
38
Primary effect of thyroid hormone is to _
Which 5 cellular responses cause, support, or are a consequence of increased metabolic rate?
Stimulate cellular metabolism
Increased metabolic rate:
⬆️ Na/K ATPase activity
⬆️ synthesis of respiratory enzymes
⬆️ substrate availability
⬆️ cellular heat production
Effects on mitochondria
39
What is the permissive effect that thyroid hormone has on catecholaminergic responses?
What is the role of thyroid hormone on growth, nervous sys. Development and function of the adult nervous system?
TH increases sensitivity to catecholamines in endocrine and nervous system
TH causes synthesis of new proteins that aid in maturation of CNS
40
What are the major causes of hypothyroidism and hyperthyroidism?
What are the symptoms associated with each?
How are they typically treated?
Hypo - caused by primary defect in thyroid. 95% involve iodine deficiency or damage to gland.
Treated with exogenous TH
Hyper - too much TH (tumor, autoimmune (graves))
Treated by removing/destroying gland
Antithyroid drugs
41
How can either hypo/hyperthyroidism result in a goiter?
Hypo - no iodine (not enough TH, no negative feedback, increase TRH/TSH)
Hyper - hyperstimulation of TSH receptor
42
What plasma concentrations of thyroid hormone and TSH would be observed in hypothyroidism due to iodine deficiency and why?
Graves’ disease?
Hyperthyroidism?
Hypo: low TH, high TSH
Graves: High TH, low TSH
Hyper: High TH, low TSH (antibodies stimulate receptors)
43
Concerns that dentists have in treating hypothyroid patient (5)
Hyperthyroid patient? (4)
Hypo:
1. Cretinism - max prognathism
2. Adults - exaggerated response to narcotics and barbiturates (not enough counteracting from symp. Nervous sys)
3. Myxedema - swelling of lips and tongue
4. Diminished cardiac/respiratory function
5. Susceptible to hypothermia and hypotension
Hyper:
1. Early eruption of teeth (malocclusion)
2. Hypersensitivity to catecholaminergic drugs (epinephrine)
3. Thyroid storm
4. Inc. susceptibility to caries/perio
44
Location of adrenal medulla vs. cortex?
Part of which nervous system?
Formed from what?
Medulla - Inner, from neural crest cells, part of SNS
Cortex - outer, from mesothelioma cells in intermediate mesoderm, not part of nervous system.
45
How does the a medulla work as a modified sympathetic ganglion?
What are the stimuli that result in release of hormones from adrenal medulla?
The gland is the ganglion. No postsynaptic neurons, instead postganglionic/chromaffin cells release epinephrine (80) and norepinephrine (20) into blood.
Stimuli from preganglionic SNS neurons
46
List the hormones secreted by the adrenal medulla, and know why the adrenal medulla secretes more epinephrine than norepinephrine
Epinephrine (80)/ Norepinephrine (20)
Medulla contains phenyl-N-methyltransferase which changes NE to E
47
Describe the organization of the three zones of the adrenal cortex.
Which of the steroid hormones are the principle products of each zone?
What is their general position in the steroid biosynthetic pathway (e.g. cholesterol to pregnenolone to cortisol/corticosterone or aldosterone or androgens).
Glomerulosa - outer
-makes aldosterone
Fasciculata - middle
-makes cortisol, corticosterone
Reticularis - inner
-DHEA/androstenedione
GFR
ACCDA
48
T/F which steroid is secreted is a consequence of the steroidogenic enzymes that are present in cells of a given zone.
TRUE
49
Describe the target tissue and actions of aldosterone to maintain blood pressure and mineral balance.
Stimulates Na and H2O retention by kidney to maintain BP and BV
Results in increased urinary excretion of K and H+
50
List the various factors that regulate aldosterone secretion, and understand how a change (increase or decrease) in each of these factors is stabilized by the action of aldosterone.
```
Stimulated by:
Increase in plasma angiotensin II
Increase in plasma K+
Decrease in plasma pH
Drop in systemic BP
```
Inhibited by:
Increased Na+ intake
Review what aldosterone does. Basically counters all these things.
51
Describe the general function of glucocorticoids (cortisol and corticosterone).
Describe the factors that control glucocorticoid secretion, including the negative feedback mechanism between cortisol and CRH/ACTH.
Increase metabolic fuel availability and use in tissues
Synthesis and secretion is stimulated by ACTH.
Cortisol has negative feedback on both CRH and ACTH
52
List the two principle androgens secreted by the adrenal gland, and know how their secretion is regulated.
Examples of effects of adrenal androgens on target tissues.
DHEA and androstenedione
Synthesis and secretion stimulated by ACTH
NOT GnRH or LH (like other sex steroids)
DHEA is weak, precursor to other sex steroids
Androstenedione is converted DHEA, non-gonadal source of testosterone and estradiol.
They both are regulators of mood, libido, hair growth, erythropoiesis and acne.
53
T/F Adrenal androgens can be converted to other steroids in males only.
FALSE, in both males and females
54
Why is the stress response considered to be a physiological adaptation that provides an organism with the ability to maintain homeostasis?
Describe the organization and regulation of the stress axis, and provide examples of stimuli that can generate a stress response.
Stress helps body respond to deviations from normal.
Axis: cortisol -> metabolic fuel
Hypothalamus
Anterior pituitary
Adrenal cortex
Stressors:
psychiatric illness
Family dysfunction
Exams
55
List the three major goals of the stress response, and describe how and where glucocorticoids act to support these goals.
Which are non-essential (inhibited by glucocorticoids)?
Maintain BP
-GCs have permissive action on B adrenergic receptors in smooth muscle to regulate blood pressure
Mobilize and increase availability of metabolic fuel
-⬆️ gluconeogenesis, proteolysis, lipolysis
Inhibit non-essential functions
-⬇️ glucose uptake in muscle/fat, ⬇️ immune responses, growth/reproduction
56
Describe the role of the sympathetic nervous system in a stress response.
Explain why chronic stress is maladaptive, often leading to conditions such as hypertension and atherosclerosis.
SNS activation causes specific organ responses and increased circulating epinephrine
Cortisol is catabolic on substrates used to produce glucose
Mobilization of fuel increases lipids in blood which, combined with ⬆️ BP from SNS, leads to atherosclerosis and hypertension
57
Explain why glucocorticoids are essential for survival.
List the various causes of adrenal insufficiency, describe some of the symptoms associated with adrenal insufficiency (including plasma concentrations of ACTH and cortisol), and explain how the condition can be treated.
Critical in maintenance of homeostasis. Body can’t always respond to deviations from normal without it.
Causes of insufficiency:
Disease
Congenital disorder
Autoimmune disorder
Pituitary problem
Glucocorticoid therapy
```
Symptoms of insufficiency:
Low cortisol, high ACTH
Weakness, lethargy, decreased appetite
Low BP
Low fasting glucose
Hyperpigmentation
```
Treat with exogenous glucocorticoids and/or dietary control
58
Describe how secondary adrenal insufficiency can be a problem for patients with ongoing corticosteroid therapy.
What are the complications that might arise due to the additional stress of dental treatment?
There may be complications with maintaining BP during anesthesia and diminished immune and inflammatory responses.
Immune suppression, hypertension, osteoporosis, increased bleeding
59
Describe the typical cause and symptoms of hypercortisolinemia or Cushing’s syndrome, including how the symptoms relate to elevated plasma concentrations of cortisol.
Explain why you might encounter an increase in periodontitis or other oral infections in hypercortisolinemic patients
Usually due to a pituitary tumor (or too much exogenous)
Excessive tissue catabolism (bone, skin, muscle)
Diabetes like symptoms (⬆️ circulating glucose)
Impaired immune function
Hypertension
Impaired immune function
60
Primary sex hormone of male/ primary sex hormone of female
Where in biosynthetic pathway are they?
Male: Testosterone
Female: progesterone and Estradiol
Progesterone -> -> androstenedione -> Testosterone -> estradiol
61
Which enzymes convert
testosterone to dihydrotestosterone
testosterone to estradiol
androstenedione to estrone
T to DHT: 5alpha reductase
T to estradiol: aromatase
Androstenedione to estrone: aromatase
62
Reproductive or HPG axis
Hypothalamus: GnRH
Anterior pit: FSH, LH
Gonads: sex hormones, make gametes
63
Where are leydig cells in testes?
What do they do?
What stimulates testosterone secretion?
What is testosterone used for? Including feedback
Outside seminiferous tubules
Make Testosterone
LH stimulates T prod.
T regulates spermatogenesis, sexual behavior, secondary sex characteristics
Negative feedback on hypothalamus and ant. Pit
64
Where are Sertoli cells in testes?
How does spermatogenesis work there?
Androgen binding protein:
Hormone secretion, including negative feedback on FSH by ant pit
Epithelial cells lining seminiferous tubules
Regulate spermatogenesis, make pep. Hormone inhibin
ABP: helps sequester T in the testis so spermatogenesis is continuous
Inhibin has negative feedback actions on FSH by ant pit
65
What are the effects of testosterone within reproductive system?
How does T affect bone, muscle, and erythropoiesis?
Regulates spermatogenesis
Regs bone growth
Stimulates muscle growth and erythropoiesis in females and males
66
T/F some of the effects of testosterone are due to its conversion to DHT or estradiol by target tissues
TRUE
67
Where are theca cells compared to an ovarian follicle?
How do they produce steroids?
- what stimulates androgen synthesis and secretion
- what are androgens used for
Surround each follicle
LH stimulates androstenedione synthesis and diffusion into granulosa cells
Androstenedione is converted to estrone and estradiol in granulosa cells
68
Where are granulosa cells in the ovary?
How do they affect oogenesis, follicular growth, and hormone secretion?
Feedback effects of estradiol and inhibin
Epithelial cells of the follicle
FSH makes granulosa cells convert androstenedione to estrone which is converted to estradiol.
Estradiol:
Stimulates granulosa cell funct. And replication
Regulates oocyte dev.
Regulates female secondary sex charact.
Regulates bone turnover and arterial funct.
Inhibits GnRH/LH secretion
Estradiol neg. feedbacks hypothalamus
Estradiol and inhibin neg feedback ant. Pit.
69
How and when does the corpus luteum form?
Which hormones are secreted by corpus luteum?
How is their production and secretion regulated?
After ovulation, theca and granulosa cells from follicle transform into cells of corpus luteum
CL secretes E2 and p
LH causes synthesis of androstenedione
FSH causes E2 formation and inhibin
Inhibin and E2 neg feedback to turn off FSH, LH, GnRH
70
Endocrine changes and events in an ovarian cycle?
Which structures or cells are producing ovarian steroids at which points of the cycle?
When and why is gonadotropin secretion inhibited?
1/2: gonadotropin rise, follicular development
3/4/5: E2 and Inhibin increase
6/7/8: FSH decreases, E2 peaks, LH surges
9/10/11: meiosis 1 done, ovulation, CL formation
12/13: increase E2 and P, inhibit gonadotropins
14/15/16: CL regression, decrease steroids, gonadotropins rise again
71
What hormone stimulates the preovulatory surges of GnRH and LH?
Which endocrine event results in menstruation?
E2 has positive feedback on GnRH and LH
Steroid support for uterine endometrium is lost
72
Follicular and luteal phases of ovarian cycle
Vs.
Proliferative, secretory, and menstrual phases of uterine cycle
Menstrual + proliferative of uterine = follicular
Secretory = luteal
73
What effects are the ovarian steroids having on the endometrium?
E2 stimulates proliferation of endometrium
74
What is the source of the endocrine signal that prevents regression of the corpus luteum during early pregnancy, where does it come from?
Placenta makes human chorionic gonadotropin (similar to LH) to maintain luteal steroid production until placenta develops
75
What is the cause of ovarian failure leading to menopause?
What are the endocrine consequences?
Loss of ovarian follicles due to atresia
Lose ovarian steroids
Gonadotropin and inhibin secretion very high
Increase reliance on adrenal steroids
76
How does genetic sex determine gonadal development?
Why does differentiation of the genitalia depend on production of hormones by the fetal testes?
Y chromosome encodes for SRY protein
SRY directs the indifferent gonad to become a testis
Fetal testis makes T and Mullerian inhibiting substance
T stimulates proliferation of wolffian ducts, absence of T causes regression of wolffian system
77
What are the endocrine defects and resulting genotype/phenotype mismatches that are associated with congenital adrenal hyperplasia?
With 5-alpha reductase deficiency?
Androgen insensitivity?
CAH: adrenal enzyme deficiency, excess adrenal androgens. Genotype XX, phenotype if virilized (more male than female)
Effects on gonad and internal genitalia
5ar def.:no DHT, no penis, scrotum or prostate gland, XY
Phenotype is female at birth until early puberty
Effects on gonads and internal genitalia
AI: lack functional androgen receptor (used by T/DHT)
No differentiation of genitalia
XY genotype
Phenotype is female, effects gonads and int. Genitalia
78
Why are pregnant women susceptible to gingivitis and periodontal disease?
Elevated steroid hormones
