1
Q
2 functions of endocrine system
A
- coordination of physiological processes
- long distance communication
2
Q
which 2 system are in charge of coordination of physiological processes
A
CNS and endocrine
3
Q
endocrine signaling
A
involves hormone secretion into the blood by an endocrine gland, transported to a distant target site
4
Q
neuroendocrine signaling
A
involves hormone secretion into the blood by a nerve cell, transported to a distant target site
5
Q
2 types of systemic signaling (involving cascades)
A
endocrine and neuroendocrine signaling
6
Q
local signaling
A
hormone does not have to enter systemic circulation
7
Q
2 types of local signaling
A
paracrine and autocrine
8
Q
paracrine signaling
A
substance released from 1 cell type interacts with neighbouring type 2 target cell
9
Q
autocrine signaling
A
cell produces the hormone and has the corresponding receptor so will bind to itself
10
Q
example of autocrine signaling
A
growth factor
11
Q
6 steps of communication by hormones
*all applies to neurohormones too
A
- synthesis of hormone by endocrine cells
- release of hormone by endocrine cells
- transport of hormone to target site by bloodstream
- detection of hormone by specific receptor protein on target cells
- change in cellular metabolism triggered by hormone-receptor interactions
- removal of the hormone, which often terminates the cellular response
12
Q
what is important about the 6 steps of communication by hormones
A
they can each be a point of control
13
Q
9 classical endocrine organs
A
- ovaries
- testes
- hypothalamus
- anterior + posterior pituitary
- thyroid gland
- parathyroid gland
- heart
- adrenal gland
- pancreas
14
Q
how does hypothalamic-pituitary signaling occur
A
via blood vessels of pituitary stalk
15
Q
hypothalamic-hypophyseal portal system
A
from hypothalamus to adenohypophysis (anterior pituitary)
16
Q
how many hormone-producing cells in the anterior pituitary do hypothalamic neurohormones activate/inhibit
A
1/6
17
Q
releasing hormones/factors
A
induce release of other hormones from pituitary
18
Q
inhibiting hormones/factors
A
inhibit release of other hormones from pituitary
19
Q
peptide and protein hormones (glycoproteins and polypeptides)
A
we have a gene in genome to build that hormone
20
Q
steroid, amine and ionic calcium hormones
A
we have a gene that encodes enzymes that are necessary for biosynthesis of that hormone
21
Q
why is ionic calcium considered a hormone
A
because we have a calcium-sensing receptor
22
Q
where are protein hormones synthesized
A
on ribosomes as preprohormones
23
Q
what characterizes preprohormones
A
extended N-terminal sequences
24
Q
what is the purpose of the extended end-terminal sequences
A
directs them into secretory system
25
when is preprohormone sequence removed & why
removed during secretion, allows for mature hormone release
26
structure of steroid hormone
4 carbon ring structure
27
4 examples of steroid hormone
cortisol, aldosterone, testosterone, estradiol
28
what is a precursor for estradiol and how does it become that way
testosterone; aromatase burns off methyl group to turn it into an alcohol
29
where are thyroid hormones produced and what do they bind to
produced by thyroid, bind to thyroid hormone receptor
30
2 thyroid hormones
3,5,3',5'-tetraiodothyronine (T4)
3,5,3'-triiodothyronine (T3)
31
why is 3,3',5'-triiodothyronine (rT3) not considered a thyroid hormone
because it cannot bind to the thyroid receptor
32
what does T4/T3 refer to
the number of iodines on the thyroid hormone
33
percentage of T4 vs T3
T4 = ~90%
T3 = ~9%
34
lock and key mechanism
receptors are specific to the binding of only their corresponding hormone
35
4 properties of hormone receptors
- specificity
- affinity
- saturability
- measurable biological effect
36
specificity of hormone receptor
recognition of single hormone / family
37
affinity of hormone receptor
binding hormone at its physiological concentration
38
why is affinity crucial
because we need less binding when there is less hormone
39
saturability of hormone receptor
should have finite number of receptors
40
measurable biological effect of hormone receptor
measurable response due to interaction of hormone with its receptor
41
receptor upregulation
increased signaling/activity
42
how to upregulate a receptor (2)
increasing activity/responsiveness
increasing synthesis (no. of receptors)
43
receptor downregulation
decreased signalling/activity
44
how to downregulate a receptor (2)
decrease activity/responsiveness
decrease synthesis (no. of receptors)
45
3 ways for hormone to exert effects
- direct effects on function at cell membrane
- signalling via intracellular second messenger
- intracellular genomic action
46
example of hormone having direct effects on function at cell membrane
insulin and glucose
47
which of the 3 ways of hormones exerting effects is least common
direct effects on function at cell membrane
48
which of the 3 ways of hormones exerting effects is most common and why
signalling via intracellular second messenger because so many G proteins
49
example of signalling via intracellular second messenger
G protein activation turns ATP into cAMP (secondary messenger) to activate protein kinase
50
what are the effects of signalling via intracellular second messenger
biological effects on protein transcription
51
intracellular genomic action
signalling by nuclear receptors, includes receptors for steroid hormones
52
how does intracellular genomic action work
steroids can enter cells (unlike glucose) and enter nucleus/cytoplasm directly to regulate transcription of specific genes
53
effect of intracellular genomic action
change cell protein content and the way the cell functions
54
what is hormone secretion regulated by
feedback mechanisms
55
what does excess of hormone lead to
diminution of hormone secretion
56
what does hormone deficiency lead to
increase of hormone secretion
57
2 examples of negative hormone feedback loops
- Ca++ acts in negative feedback loop to regulate plasma calcium
- CRH and ACTH work in negative feedback loop to regulate plasma cortisol levels
58
CRH name
corticotropin-releasing hormone
59
ACTH name and function
adrenocorticotropic hormone (stimulates cortisol release)
60
2 distinct tissues of pituitary gland
adenohypophysis and neurohypophysis
61
adenohypophysis
anterior pituitary/pars distalis = endocrine tissue
62
neurohypophysis
posterior pituitary/pars nervosa = neural tissue
63
what is pituitary gland protected by
bone
64
which of the pituitary hormones is different from the others and why
PIH/dopamine because it is an amine (we don't have a gene for it)
65
what class do all pituitary hormones belong to except 1
peptides
66
2 posterior pituitary hormones
arginine vasopressin
oxytocin
67
what do the posterior pituitary hormones have in common
involved in smooth muscle tone but for physiologically diff conditions
68
arginine vasopressin
maintains BP
69
oxytocin
reproductive endocrinology
70
what is the posterior pituitary gland
outgrowth of hypothalamus connected by pituitary stalk
71
antidiuretic hormone (ADH) / vasopressin function
increases BP, leads to fluid retention and less peeing
72
where are oxytocin and ADH synthesized
supraoptic nucleus and paraventricular nucleus
73
where do the axons of the supraoptic nucleus and periventricular nucleus run down and terminate
axons run down pituitary stalk and terminate in posterior pituitary close to capillaries
74
when and where are the prohormones of oxytocin and ADH processed
processed in secretory granules during axonal transport
75
where are the mature forms of oxytocin and ADH liberated from
carrier molecules (neurophysins)
76
what are the circulating half lives of ADH and oxytocin
1-3 mins
77
3 functions of oxytocin in women
parturition
milk ejection
behavioural effects
78
oxytocin function in parturition
uterus sensitive to oxytocin at end of pregnancy; dilation of uterine cervix by fetal head causes oxytocin release to allow for uterine contraction
79
oxytocin function in milk ejection
infant suckling stimulates oxytocin production, causes milk filled ducts to contract and squeeze milk out
80
oxytocin function in behavioural effects
'love hormone'; local release in brain reduces anxiety and enhances bonding and prosocial behaviour
81
2 functions of oxytocin in men
ejaculation
behavioral effects
82
oxytocin function ejaculation
oxytocin surge during sexual activity assists epidimial passage of sperm
83
typical thyroid gland size
15-20g
84
why does size of thyroid gland vary with (4)
sex, age, diet, reproductive state
85
how much thyroid do we really need to maintain euthyroid state
3g
86
who has larger thyroids
females
87
colloid
viscous fluid in the central cavity of thyroid follicles containing thyroglobulin
88
thyroglobulin
glycoprotein that contains tyrosine
89
what stores T3 and T4 prior to release
colloid
90
what happens to T3 and T4 once they leave colloid
split off thyroglobulin and enter blood where they bind to special plasma proteins
91
what controls synthesis of thyroglobulin
TSH
92
why can rT3 not bind to the thyroid hormone receptor
because it does not have the diiodination of proximal benzene ring
93
what is necessary for binding to thyroid receptor
iodine
94
what traps idodie and actively transports it across the cell against chemical gradient
thyroid follicular cells
95
why is it necessary to store iodide
the supply is limited to terrestrial vertebrates
96
what happens to iodide once in the thyroid (&how)
oxidized to iodine (I2) using ATP inside follicular cells
97
what happens to iodine once it is produced
binds to tyrosine of thyroglobulin
98
1 iodine + tyrosine =
MIT (monoiodotyrosine)
99
2 iodines + tyrosine =
DIT (diiodotyrosine)
100
oxidative coupling of 2 DIT =
T4
101
oxidative coupling of 1 DIT + 1 MIT =
T3
102
what happens when there is an increase in TSH
there is an increased rate of all the steps involved in T3 + T4 formation
103
what does low TSH mean
low turnover of thyroid homones
104
what is the synthesis and release of TSH controlled by
hypothalamic thyrotropin releasing hormone (TRH)
105
result of increased T3 + T4 in blood =
double negative feedback at hypothalamic and pituitary levels to decrease TRH and TSH release, and decrease T3 and T4 production
106
result of decreased T3 and T4 in blood =
TSH interacts with specific receptors located on follicular cells to increase T3 and T4 production
107
2 effects of iodine deficiency
- decreased thyroid hormone synthesis (lower conc of T3 and T4 in circulation)
- increased TSH release
108
result of increased TSH release
constant stimulation of thyroid follicular cells, leads to enlarged thyroid (may form goiter)
109
non toxic goiter
enlarged thyroid unable to synthesize biological active thyroid hormones due to iodine deficiency
110
3 effects of thyroid hormones on calorigenesis
increased cardiac output
increased blood oxygenation
increased breathing rate and number of circulating red blood cells
111
2 effects of thyroid hormones on carb metabolism
promotes glycogen formation in liver
increased glucose uptake into muscle and adipose tissue
112
effect of thyroid hormone on lipid turnover
increase lipid synthesis, mobilization and oxidation
113
effect of thyroid hormone on protein metabolism
stimulates protein synthesis
114
3 effects of thyroid hormones on normal growth
promotes normal branching and nerve myelination
promotes nervous system development and maturation
stimulates GH secretion, bone growth and IGF-1 production
115
lack of normal growth due to thyroid deficiency =
cretinism
116
2 most important thyroid hormone functions
increase basic metabolic rate
normal linear growth
117
what are 90% of molecular mechanisms of action of thyroid hormone
analogous to steroid hormones = T3 and T4 enter cell nucleus, bind to cognate nuclear receptor and alter specific gene transcription
118
2 other molecular mechanisms of action of thyroid hormone
- may induce some effects by interactions with plasma membrane and mitochondria (specific T3/T4 receptor located in inner mitochondrial membrane)
- act directly at plasma membrane and increase amino acid uptake
119
what do the 2 other molecular mechanisms of action of thyroid hormone have in common
they are independent of protein synthesis
120
how to protect yourself from nuclear power plant
excess stable iodine (127I) is used to protect thyroid gland from radioactive isotopes by saturating iodine transport system (isotopically dilutes amount of radioactive iodine entering gland)
121
what is used to treat thyroid cancer
radioactive iodine
122
hypothyroidism
low levels of thyroid hormones
123
primary hypothyroidism (myxedema)
inability to synthesize active thyroid hormones (thyroid level)
124
who is primary hypothyroidism more common in
women 40-60y
125
3 causes of primary hypothyroidism
- thyroid atrophy (idiopathic)
- autoimmune thyroiditis / Hashimoto's disease
- goitrous hypothyroidism / non-toxic goiter
126
autoimmune thyroiditis / Hashimoto's disease
destruction by antibodies against cellular components of thyroid (more common in women, most common cause)
127
goitrous hypothyroidism / non-toxic goiter
blockage in a step of T3/T4 synthesis leading to growth of thyroid gland (decreased T3/T4, increased TRH and TSH)
128
secondary hypothyroidism
synthesis of little to no TSH (pituitary level)
129
tertiary hypothyroidism
synthesis of little to no TRH (hypothalamus level)
130
infantile hypothyroidism
absence of thyroid gland/ incomplete development of thyroid gland at birth
131
why are some babies normal at birth when they have infantile hypothyroidism
use mother's T3/T4 but once born, can no longer produce their own therefore exhibit less physical growth and mental development
132
why does infantile hypothyroidism require immediate treatment
will exhibit dwarfism and cretinism
133
what can all forms of hypothyroidism be treated with
administration of thyroid hormones
134
hyperthyroidism
high levels of thyroid hormones
135
primary hyperthyroidism
at thyroid gland level
136
2 causes of primary hyperthyroidism
toxic diffuse goiter (Graves disease) and thyroid adenoma / thyroid cancer
137
toxic diffuse goiter (Graves disease)
autoimmune disease characterized by presence of substance produced by lymphocytes (LATS)
138
long acting thyroid stimulator / LATS
antibody that mimics TSH action, stimulates T3+T4 release
139
what does constant stimulation by LATS lead to (primary hyperthyroidism)
increased thyroid mass and toxic goiter formation
140
what makes a goiter toxic
in continues to synthesize biologically active T3/T4
141
does the negative feedback loop work in Graves disease
yes, the increase in thyroid hormones leads to less TRH and TSH, but LATS prevents reduction in T3/T4 synthesis
142
thyroid adenoma / thyroid cancer
synthesis of thyroid hormones independent of TSH stimulation (very curable)
143
secondary hyperthyroidism
no negative feedback from increased T3 and T4 (hormones synthesize independently of TSH (anterior pituitary level)
144
what is the most common cause of secondary hyperthyroidism
pituitary tumor
145
tertiary hyperthyroidism
no negative feedback of increased T3 and T4 to decreased TRH secretion (hypothalamus level)
146
what is the most common cause of tertiary hyperthyroidism
hypothalamic tumor
147
3 treatments for hyperthyroidism
- surgery and administration of thyroid hormones
- administration of radioactive iodide (131I) to destroy hormone-producing cells
- administration of antithyroid drugs like propylthiouracil to block addition of iodine to thyroglobulin (block hormone synthesis)
148
what determines which hyperthyroidism treatment you pick
severity of disease
149
abnormalities of thyroid gland can be ...
congenital or acquired
150
6 roles of calcium ions
- skeletal structure
- blood clotting
- maintain transmembrane potentials
- excitability of nervous tissue
- muscle contraction
- hormone and neurotransmitter release
151
where is 99% of our calcium found
loosely bound in bone
152
what is normal conc of calcium in cellular and extracellular fluid
~10mg/100 mL
153
what is the distribution of free calcium to calcium bound to albumin
50-50
154
where is calcium obtained
diet (dairy)
155
where is calcium absorbed from digestive tract into plasma
duodenum and upper jejunum
156
what 2 things increase absorption of calcium in intestine
vitamin D and PTH
157
where is some calcium excreted directly
feces
158
calcitonin function
deposits calcium in bone or tissue cells when concentration high
159
where does calcitonin cause some calcium to be lost
moves through kidney, lost in urine
160
what is the effect if calcitonin
decreased circulating calcium
161
what happens if calcium conc is less than 10mg/100mL (2)
PTH stimulates reabsorption of calcium from kidney and removal of calcium from bone and tissues (resorption)
162
what is calcium conc maintenance determined by
exchange between bone and plasms under hormonal influence
163
parathyroid hormone (PTH)
protein produced by parathyroid gland, increases circulating calcium
164
calcitonin
protein produced by thyroid gland C cells, lowers circulating calcium
165
vitamin D function
stimulates calcium uptake from digestive tract to increase circulating calcium conc
166
where is parathyroid hormone secreted from
parathyroid chief cells embedded in thyroid surface
167
how many parathyroid glands glands do we have and where are they
4 glands on back side of thyroid
168
what does removing the parathyroids do (2)
decrease plasma calcium levels, leading to tetanic convulsions and death
169
how big is PTH
84 amino acid polypeptide
170
how much of PTH do we need for full activity and why
N-terminal 34 amino acids (it is the receptor binding portion)
171
what is PTH synthesized as a part of, and how does it become PTH
preproparathyroid hormone undergoes proteolytic cleavage to produce PTH
172
what is PTH half life
3-18 min
173
PTH function
increase plasma Ca++ conc
174
4 ways PTH increases plasma Ca++
- bone resorption (increase bone demineralization)
- kidney (increase reabsorption of Ca in proximal convoluted tubule)
- vitamin D synthesis (stimulates conversion of 25-hydroxy D3 to 1,25 D3)
- gut (facilitate absorption of Ca from gut to blood)
175
what is PTH release controlled by
circulating Ca++ conc
176
what does PTH bind to (&where)
cognate receptors on target cell exerts
177
hypoparathyroidism
decreased levels of PTH in circ
178
4 symptoms of hypoparathyroidism
- hypocalcemia
- decreased 1,25 D3 production
- tetany/convulsions
- if Ca++ < 7mg/100mL = increased neural overexcitability and muscle spasms
179
why is severe hypoparathyroidism very dangerous
laryngeal muscle spasms can lead to death by asphyxiation
180
hypoparathyroidism treatment
1,25D3 administration and calcium supplements
181
hyperparathyroidism
increased levels of PTH in circ
182
what is hyperparathyroidism often caused by
parathyroid adenoma of parathyroid. producing too much PTH
183
3 effects of hyperparathyroidism
- increased 1,25D3 production = calcium absorption from intestines
- bone resorption & calcium reabsorption from kidney
- kidney stones
184
3 symptoms of severe hyperparathyroidism
- cardiac arrhythmias
- depressed neuromuscular excitability
- calcium deposition on walls of blood vessels
185
hyperparathyroidism treatment
removal of affected parathyroids and replacement therapy of 1,25D3 and Ca++
186
where do we get vitamin D from (2)
limited dietary sources (cod liver oil, fatty fish) and can be synthesized from cholesterol metabolite (therefore not strictly a vitamin)
187
when is vitamin D high
when Ca++ is low and PTH is high
188
what is vitamin D depressed by
increased Ca++
189
4 steps to vitamin D synthesis
- UVB light + 7-dehydrocholesterol in skin
- 25-hydroxylation in liver
- 1-hydroxylation in kidney and tissues
- 1,25D3
190
3 physiological functions of vitamin D
- increase Ca++ absorption from intestine
- regulate immune system
- anticancer properties
191
why do northern countries have deficient bone mineralization
absence of UVB leads to vitamin D deficiency
192
vitamin D deficiency in growing individuals
rickets
193
who is more likely to be vitamin D deficient and why
dark-skinned individuals because make less vitamin D from given sun exposure
194
vitamin D deficiency in adults
osteomalacia (soft bone)
195
hereditary vitamin D-resistance rickets
due to inactivating mutation in vitamin D receptor
196
3 symptoms ofhereditary vitamin D-resistance rickets
shortened clavicle
shortened ribcage
baldness
197
which symptoms will be different in someone who lacks the enzyme for vitamin D, not the receptor
no baldness
198
calcitonin structure
32 amino acid polypeptide (all 32 necessary)
199
where is calcitonin produced
parafollicular / "C" cells of thyroid gland
200
what controls calcitonin release
high plasma calcium = high calcitonin
low plasma calcium = low calcitonin release
201
how do we know calcitonin is less important than PTH. and1,25 D3 for calcium regulation
can remove thyroid gland and maintain calcium homeostasis
202
where are adrenal glands located
adjacent to upper surface of kidneys
203
who has bigger adrenal glands
males
204
2 distinct tissue types of adrenal glands
cortex and medulla
205
what is adrenal cortex made of
large lipid-containing epithelial cells derived from mesoderm
206
what does adrenal cortex produce
steroid hormones
207
3 zones of adrenal cortex and their hormones
- zona glomerulosa = mineralocorticoids (aldosterone)
- zone fasciculata = glucocorticoids (cortisol)
- zona reticularis = glucocorticoids, progestins, androgens and estrogens
208
what is the adrenal medulla made of
chromaffin cells (fine brown granules when fixed with potassium bichromate) derived from neural crest
209
what does adrenal medulla produce (2)
catecholamines (epinephrine and norepinephrine) and peptide hormones (enkephalins, dynorphins, atrial natriuretic peptides)
210
what is the synthesis of adrenal steroids controlled by
adrenocorticotropin (ACTH)
211
what produces ACTH
pituitary
212
why is zona glomerulosa the only one that can synthesize mineralocorticoids
because it is the only zone with 18-hydroxylase
213
why can zona glomerulosa no produce glucocorticoids
because it doesn't have 17a-hydroxylase
214
how big is ACTH
39 amino acid polypeptide
215
2 ACTH functions
- stimulates adenylyl cyclase to increase cAMP production
- activates steroidogenic enzymes to increase synthesis and release of steroid hormones
216
what 2 substances have circadian pattern and what does this mean for them
plasma cortisol and ACTH
have a built-in feedback loop delay
(lowest at midnight, max in morning but independent of sleep)
217
what abolishes plasma cortisol and ACTH circadian pattern (2)
stress and Cushing's disease
218
steroid hormones
regulate the transcription of hormones or receptor-specific target genese
219
2 adrenal hormones
aldosterone and glucocorticoids
220
aldosterone function
sodium metabolism (increases reabsorption of Na+ by kidney)
221
what must happen for aldosterone to affect sodium metabolism
coupled with Cl- during removal or replaced by K+/H+
222
4 glucocorticoid functions
- salt retention
- protein and carb metabolism (PRIMARY FUNCTION)
- lipid metabolism
- anti-inflammatory and immunosuppressive actions
223
which adrenal hormone is more effective at salt retention
aldosterone
224
how are glucocorticoids involved in protein and carb metabolism (2)
- stimulate synthesis of enzymes that break down tissue protein
- decrease glucose uptake by muscle and adipose tissue and decrease glycolysis
225
what happens when glucocorticoids stimulate synthesis of enzymes that break down tissue protein (2)
- amino acids are converted to glucose and glycogen (gluconeogenesis) when they enter. the liver
- can decrease protein matrix and lead to osteoporosis
226
what happens when glucocorticoids decrease glucose uptake by muscle and adipose tissue and decrease glycolysis (3)
- conserve glucose for other tissues
- causes increased blood glucose (adrenal diabetes)
- prolonged adrenal diabetes can lead to destruction of beta cells in pancreas and diabetes mellitus
227
2 glucocorticoid effects on lipid metabolism
- maintain or increase lipolitic enzyme levels in adipose tissue
- increase lipolytic action of other hormones
228
what does glucocorticoid excess lead to in terms of lipids (2)
hyperlipidemia and hypercholesterolemia
229
3 glucocorticoid anti-inflammatory and immunosuppressive effects
- decreased inflammatory response
- atrophy of lymphatic system
- decreased histamine formation = less allergic reactions
230
why are glucoccorticoids used in organ transplantation
because decreases number of circulating lymphocytes and antiboy formation, therefore helps avoid organ rejection
231
what is glucocorticoid secretion controlled by
ACTH
232
what does the cortisol double negative feedback loop connect
hypothalamus (CRH) and anterior pituitary (ACTH)
233
congenital adrenal hyperplasia
enzyme deficiency that leads to cortisol not being produced and ACTH secretion is unchecked
234
congenital adrenal hyperplasia treatment
administer cortisol to correct deficiency and normalize ACTH secretion
235
what does psychological and physical stress lead to
increased CRH, ACTH and cortisol synthesis and release
236
advantage of increased cortisol
more energy and amino acids by tissue protein breakdown
237
disadvantage of increased cortisol
inhibits wound healing
238
Addison's disease
hypofunction of adrenal cortex (failure to produce adrenocortical hormones cortisol and aldosterone)
239
what is Addison's disease mainly caused by
autoimmune attack on adrenal glands (or tuberculosis)
- may involve total gland destruction
240
symptoms of cortisol/glucocorticoid deficiency (Addison's disease) (6)
low blood sugar, low lipolysis, low gluconeogenesis
lack of energy, muscular weakness, inability to take stress
241
treatment for cortisol/glucocorticoid deficiency (Addison's disease)
cortisol to help carbohydrate metabolism
242
symptoms of aldosterone/mineralocorticoid deficiency (Addison's disease) (7)
low Na+, Cl-, H2O
low extracellular fluid, low cardiac output
increased K+, H+
243
what happens after 7 day complete absence of mineralocorticoids
die
244
treatment for aldosterone/mineralocorticoid deficiency (Addison's disease)
aldosterone to control electrolyte blood levels
245
Cushing's disease
hyperfunction of adrenal cortex (increased production of glucocorticoids and mineralocorticoids)
246
what is the cause of Cushing's disease
increased circulating ACTH levels (pituitary/adrenal tumor), leads to hyperplasia/growth
247
effects of increased glucocorticoid production (Cushing's disease) (4)
increased blood glucose (adrenal diabetes), insulin secretion, protein breakdown = osteoporosis
248
effects of increased mineralocorticoid production (Cushing's disease) (6)
increased Na+, Cl-, H2O, plasma volume, extracellular fluid, hypertension
249
why can Cushing's disease lead to masculinization
increased sex hormones and androgens
250
Cushing's disease diagnosis (6)
puffy face, masculinization, hypertension that does not respond to BP medication, high blood glucose and steroid metabolites in urine, undetectable ACTH, high circulating cortisol
251
Cushing's disease treatment
subtotal removal of adrenal cortex
252
what can sometimes happen after removing adrenal tumor
atrophy of other adrenal because loss of circulating ACTH (Addison's diseasE)
253
treatment after removing adrenal tumor
synthetic glucocorticoids and mineralocorticoids
254
where is pancreas
behind stomach
255
what is 99% of pancreas
exocrine = secretes digestive enzymes
256
what is 1% of pancreas
islets of Langerhans
257
islets of Langerhans
endocrine structure; compact cells with good vascularization
258
60% islets of Langerhans
beta cells = synthesize insulin
259
25% islets of Langerhans
alpha cells = synthesize glucagon
260
insulin
only hormone that acts primarily to decrease blood glucose (IMPORTANT)
261
fasting glucose level
80mg/100mL (always present in blood)
262
why must glucose be transported into cells by membrane proteins
because it is hydrophilic
263
what does stimulation of insulin receptors lead to
inserts glucose transport protein onto cell surfaces to increase glucose uptake
264
what happens as we eat to induce insulin secretion before blood glucose increases
release of gastrin and vagal impulses to beta cells
265
what does glucose become in liver and muscle cells
glycogen
266
what does glucose become in adipose tissue
fat
267
what does glucose become in other body cells
oxidized to produce ATP
268
insulin deficiency
destruction of beta cells leads to diabetes mellitus
269
diabetes mellitus
most tissues cannot take up glucose efficiently, glucose accumulates in circ
270
will glucose accumulate in circ even if not ingested
yes because increased gluconeogenesis will occur (protein breakdown)
271
what becomes main energy source in insulin deficiency
free fatty acids (FFA), but inefficently used
272
what does incomplete FFA oxidation lead to (3)
increased circulating acetoacetic acid and metabolic acidosis, and acetone
273
what is one way to tell someone has extreme untreated diabetes
smell acetone in breath
274
what are consequences of incomplete FFA oxidation (3)
decreased blood pH, diabetic coma and death
275
glucose >180mg% (3)
glucose in urine
loss of water in urine
dehydration and increased thirst
276
treatment for diabetes mellitus
insulin administration (may also need to correct acidosis and electrolyte imbalance if extreme)
277
type 1/insulin-dependent diabetes mellitus
insulin deficient
278
2 causes of type 1 diabetes
beta cella destruction (no insulin synthesis) and defective insulin release
279
treatment for beta cell destruction
insulin administration and proper diet
280
treatment for defective insulin release
drugs stimulating insulin release and proper diet and exercise
281
what is considered to be low blood glucose and why
20-30mg/100mL (not enough for brain use = insulin shock/hypoglycemic coma)
282
type 2/insulin-independent diabetes mellitus
hypo-responsiveness of target cells to insulin
283
what are insulin levels like in type 2 diabetes
normal to abnormally high
284
what is insulin resistance in type 2 diabetes often due to
decreased no. of insulin receptors on target cells (downregulation)
285
what is type 2 diabetes associated with
overeating / obesity
286
treatment for type 2 diabetes
proper diet and exercise
287
juvenile diabetes mellitus
insulin-dependent; beta cells don't produce insulin
288
treatment for juvenile diabetes mellitus
insulin administration
289
glucose tolerance test
after overnight fast, administer 0.75-1.5g glucose per kg body weight, measure glucose before and every 30-60 mins for 3-4 hours
- glucose tolerance lower in diabetes, higher in hyperinsulinism
290
how does blood glucose change in normal individual
from 80mg/100mL to 130mg/mL and after 2-3 hours, returns to normal
291
how does blood glucose change in diabetic individual
increase in blood glucose is greater and returns to normal more slowly
292
what type of hormone is glucagon
peptide hormone
293
what synthesizes and releases glucagon
alpha cells of pancreas
294
2 ways glucagon raises blood sugar
glycogenolysis (breakdown of glycogen) and gluconeogenesis (glucose synthesis)
295
glucagon function in adipose tissue
increases rate of lipolysis -> increases FFA conc
296
why is it less important than insulin
other hormones can have same function e.g. cortisol, epinephrine, norepinephrine
297
what kind of hormone is growth hormone / somatotropin / STH
single chain polypeptide
298
what produces growth hormone / somatotropin / STH
anterior lobe of pituitary
299
2 growth hormone functions
- increases protein synthesis in bone, muscle, kidney, liver (enhances amino acid uptake, accelerates transcription and translation of mRNA)
- increases rate of lipolysis and utilisation of FFA as energy source
300
what is growth hormone release controlled by
hypothalamic neurohormones:
- GRH = stimulates
- somatostatin = inhibits
301
when and where are somatomedins produced
produced by liver under GH stimulation
302
what are somatomedins structurally similar to
insulin, therefore called isunlin-like growth factors 1 and 2 (IGF-1 and IGF-2)
303
somatomedin function
increase protein synthesis and stimulate growth
304
GH deficiency
leads to decreased physical growth in the young
305
excess GH in young individuals
gigantism
306
excess GH in adults
acromegaly
307
acromegaly
many bones (particularly cartilaginous regions) get longer a heavier, increased frontal bossing, brow furrow, enlargement of nose base, thickening of lips
308
where do somatomedins act in their double negative feedback loop
hypothalamus and anterior pituitary
309
primary reproductive organs
gonads
(testes = male)
(ovaries = female)
310
2 gonad functions
- gametogenesis (production of gametes - spermatozoa and ova)
- secretion of sex hormones testosterone, estrogen and progesterone (male and female)
311
where do females produce androgens (2)
ovaries and adrenals**
312
role os estrogen in males
maintains bone density
313
where is estrogen produced in males and how
testes; conversion by aromatase of testosterone to estradiol
314
estrogen deficiency in males (2)
- leads to decreased body fat
- contributes to sexual desire and erectile function
315
what secretes gonodotropin releasing hormone (GnRH)
hypothalamus
316
where does GnRH travel to and how once secreted
travels to anterior pituitary via hypothalamo-pituitary portal vessels
317
what does GnRH stimulate the release of
pituitary gonadotropins (follicle-stimulating hormone/FSH and luteinizing hormone/LH)
318
what do FSH and LH do once secreted from anterior pituitary
stimulate development of spermatozoa/ova, and secretion of sex steroids (estrogens and androgens)
319
2 locations sex steroids exert effects
- gonads
- other parts of reproductive system and body
320
what do gonads produce, and what does it do
inhibin - feeds back on anterior pituitary
321
spermatogenesis
production of mature germ cells
322
where does spermatogenesis take place
seminiferous tubules
323
testes principal functions (2)
spermatogenesis and steroidogenesis
324
how long does the process of maturation from immature spermatogonia to mature spermatozoon take in humans
approx 60 days
325
how come men have relatively constant supply of sperm throughout life
can renew pool of precursor germ cells (spermatogonia)
326
what condition is spermatogenesis dependent on
androgen concentration in seminiferous tubules being 10x greater than in circulation
327
what ensures the high androgen concentrations in seminiferous tubules
ABP synthesized by Sertoli cells
328
2 types of cells involved for maturation of spermatozoa
Leydig cells and Sertoli cells
329
where are Leydig cells located
outside seminiferous tubules
330
Leydig cell function
synthesize androgens in response to LH binding to surface receptors
331
where are Sertoli cells located
within seminiferous tubules
332
Sertoli cell functions (2)
- synthesize ABP and inhibin in response to FSH
- envelop germ cells during maturation process
333
2 negative feedback loop of testicular androgen regulation
- hypothalamic-pituitary-Leydig cell axis
- hypothalamic-pituitary-seminiferous-tubules-axis
334
hypothalamic-pituitary-Leydig cell axis (4) DOUBLE NEGATIVE
- GnRH stimulates release of LH and FSH
- LH and FSH stimulate Leydig cells and Sertoli cells
- Leydig cells produce androgens
- Androgen inhibit release of GnRH (hypothalamus), LH and FSH (anterior pituitary)
335
hypothalamic-pituitary-seminiferous-tubules axis
- GnRH stimulates release of LH and FSH
- LH and FSH stimulate Leydig cells and Sertoli cells
- Sertoli cells secrete non steroidal inhibin
- inhibin inhibits FSH release
336
2 principal functions of ovary
production of mature eggs and steroid hormones
337
function of steroid hormones in women (2)
regulate reproductive tract and influence sexual behaviour
338
how many oocytes do women have at birth
2 mil (lifetime supply)
339
how many oocytes are left at puberty
400,000 ova
340
primordial follicles
oocyte surrounded by layer of granulosa cells and basement membrane
341
what triggers development of primordial follicles into primary follicles
unsure
342
what controls the growth of primary follicles once started (2)
gonadotropins and steroid hormones
343
2 possible outcomes for primary follicle
ovulation or degeneration (atresia)
344
first step of follicular growth
primordial follicle grows and develops zona pellucida
345
zona pellucida
acellular layer rich in glycoproteins surrounding the oocyte
346
what happens once primordial follicle has developed zona pellucida
granulosa cells divide and increase in layers to become primary follicles
347
what influences primary follicle development
FSH and estrogens
348
what is important for expression of LH receptors on granulosa cells
estrogens
349
what happens after primary follicle is developed, and what influences it
FSH and LH cause primary follicle to develop into a secondary follicle that expresses receptors for FSH, estrogen and LH
350
what happens after secondary follicle is developed
appearance of follicular antrum which contains secretions from granulosa cells
351
what happens after appearance of follicular antrum and what influences it
FSH and LH cause granulosa cells to elaborate follicular fluid (large portion of preovulatory follicle)
352
what also happens as follicle matures from primary to secondary follicle
cells from ovarian stroma surrounding follicle differentiate and become theca cells (steroid producing cells)
353
what do theca and granulosa cells contribute towards
synthesis of higher amounts of estrogen
354
what does the ruptured follicle transform into
corpus luteum
355
what does corpus luteum secrete
progesterone
356
what contributes to formation of corpus luteum (2)
theca and granulosa cells
357
2 things corpus luteum synthesizes, and how much
progesterone and estrogens
- large amounts for few days following ovulation, then drop off unless implantation of fertilized ovum
358
luteolysis
corpus luteum degenerates without implantation
359
what can induce luteal regression and what effect may this have
prostaglandins; decrease LH binding and therefore steroidogenesis
360
what may be the trigger for initiation of next reproductive cycle
decrease of plasma progesterone and estrogen
361
what happens to corpus luteum upon implantation
transforms into corpus luteum of pregnancy
362
what is corpus luteum of pregnancy responsible for
synthesis of progesterone and estrogen and creation of proper endocrine environment until placenta is established
363
what causes endometrium to thicken prior to day 1 of menstrual cycle
estradiol
364
what induces appearance of specialized glycogen-secreting glands
progesterone
365
day 1 of menstrual cycle
1st day of detectable vaginal bleeding (deterioration of uterine endometrium)
366
what causes menses/bleeding to begin on day 1
low estradiol and progesterone in circ; blood vessels supplying endometrium constrict to reduce blood supply
367
what is the bleeding of menstrual cycle
endometrium deteriorates, flows through cervix into vagina
368
how long does bleeding typically last
5 days (ovaries endocrinologically inactive)
369
what leads to increased pituitary FSH secretion (2)
- low estradiol and progesterone (lack of negative feedback loop)
- decrease in inhibin
370
what does the high FSH concentration lead to (days 1-7)
cohort of ovarian follicles develops and stimulates granulosa cells of follicles to proliferate
371
what is another contributing factor of granulosa cell proliferation
granulosa cells produce estrogen
372
what happens on day 8 of cycle
1 follicle becomes dominant and committed to further development, rest degenerate
373
how does 1 follicle become dominant in humans
unknown
374
what does the dominant follicle do
produces increasingly more estradiol to stimulate uterine endometrium proliferation
375
what happens by day 13 of cycle
endometrium very thick, estradiol induces production of endometrial progesterone receptors
376
3 sections of menstrual cycle (from day 1)
menstrual, proliferative, secretory
377
2 phases of menstrual cycle
follicular and luteal
378
3 effects of moderate estradiol concentrations
- negative feedback on FSH
- stimulates synthesis of LH by pituitary
- increase sensitivity of pituitary to GnRH
379
why does LH accumulate in pituitary at moderate estradiol concs
because it stimulates synthesis but inhibits release of LH
380
what causes estrogen concentration to continue to build
developing follicle
381
what do high estrogen concs do (and when)
stimulate LH release (LH surge) on day 14
382
estrogen positive feedback control mechanism
stimulation of LH synthesis by estradiol + increased sensitivity of anterior pituitary to GnRH = increased LH synthesis
383
what does LH surge do
causes follicle to rupture (mechanism unclear) and ovum is ejected
384
what do oral contraceptive pills contain (2)
estrogen and progesterone
385
why do oral contraceptives work
maintain moderate circulating levels of estrogen and progesterone to suppress release of LH and FSH from pituitary -> prevents ovarian follicles from maturing and being ovulated
386
oral contraceptive success rate when taken correctly
99%
387
luteal phase (& duration)
steroids produced by corpus luteum dominate (lasts 14 days)
388
what happens after 14 days with no implantation and corpus luteum degenerates (4)
- steroid levels drop
- uterine endometrium degenerates
- menstruation begins
- pituitary starts to increase FSH secretion
389
where is unfertilised egg taken to at ovulation
fallopian tube, propelled towards lumen of uterus
390
up to what point will spermatozoa travel to fertilize the egg
oviduct
391
when/where does egg start dividing into blastocyst
during its transport down the oviduct into uterine lumen
392
what does blastocyst differentiate into (2)
trophoblast and inner cell mass
393
what does trophoblast become
placenta
394
what does inner cell mass become
embryo
395
what does trophoblast do to embed developing embryo in endometrium
invades uterine mucosa
396
what does trophoblast start to synthesize around the time of implantation
human chorionic gonadotropin (hCG)
397
human chorionic gonadotropin (HCG) (2)
has LH-like properties, stimulates corpus luteum to continue secreting gonadal steroids
398
what happens at 12th week of pregnancy
placenta takes over the endocrine function of corpus luteum
399
what quickly appears in blood and urine, and what is this basis for
HCG; basis for immunological pregnancy test
400
lactation
secretion of milk by breast (mammary glands)
401
what is required for lactation
normal mammary development
402
what happens for mature non-pregnant mammary gland (ductal) development
with puberty and increasing estrogen levels, duct growth enhancement and duct branching
403
what stimulates growth of alveoli in mature non-pregnant mammary glands
alveoli
404
what is most breast enlargement due to in mature non-pregnant mammary glands
fat deposition under glandular tissue
405
what allows ductal and alveoli structures to fully develop (4)
estrogen, progesterone, prolactin and human placental lactogen
406
what controls milk production during pregnancy
prolactin
407
what inhibits milk secretion
high estrogen levels
408
what happens to prolactin and estrogen levels after parturition
estrogen levels decrease, prolactin levels remain high
409
what do the low estrogen and high prolactin levels allow for
milk synthesis, then alveoli secrete it to fill the ducts
410
nursing
under action of oxytocin, ducts contract to cause milk ejection
411
prolactin (what produces it & function)
anterior pituitary - milk production
412
oxytocin (what produces it & function)
posterior pituitary - milk ejection
413
what is milk made of (5)
water, protein, fat, carbohydrate lactose and antibodies
414
lactational amenorrhea
maintained nursing stimulates prolactin production which inhibits the secretion of FSH and LH - blocks resumption of reproductive cycle therefore can be used as contraception
415
menopause
loss of ovarian steroid production
416
why can ovaries no longer produce estrogen and progesterone
most follicles depleted / disappeared through atresia
417
4 symptoms of lack of estrogen
hot flashes, dry vagina, restlessness and bone loss
418
what is indicative of menopause and why
high FSH conc; cessation of ovarian steroid hormone production eliminates negative feedback loop
419
how to cure estrogen deficiency symptoms (but what is limitation)
estrogen replacement threapy, but fertility cannot be restored
420
what is similar in structure to cholesterol
provitamin D3 (sensitive to UVB radiation)
421
what is provitamin D3 converted to
vitamin D3
422
what is vitamin D3 then converted to (& what does the conversion)
liver converts vitamin D into 25-hydroxy-vitamin D3
423
what is major circulating form of vitamin D
25-hydroxy-vitamin D3
424
what happens to 25-hydroxy-vitamin D3 in peripheral tissues
1-hydroxylation occurs - makes it 1,25-dihydroxy-vitamin D3 (active form that binds to receptors)
425
what condition does the sun have to meet for UVB synthesis to occur
40 degress
426
why is there vitamin D deficiency in the middle East
because it's so hot that people avoid the sun
427
3 conditions that have shown north-south gradients
1. certain types of cancers
2. autoimmune diseases
3. infectious diseases
428
what types of cancers show north-south gradient and why
digestive cancers and leukemias; places with elevation are more vitamin D sufficient therefore see reduction in colon cancer
429
example of autoimmune disease with north-south gradient
multiple sclerosis
430
what causes immune system cells (macrophages) to become responsive to 25D3
sensing presence of bacterial cell wall
431
treatment of cells with 1,25 D3 induces what
secretion of antibacterial activity in the form of antimicrobial proteins
PHGY 210
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