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328 Cards in this Set

  • Front
  • Back
What are the types of hormones?
Protein/peptide hormones
Steroid hormones
Amine hormones
How are protein and peptide hormones synthesized?
Preprohormone synthesis occurs in the ER
The signal peptide is cleaves to give the prohormone
The prohormone trafficks to the Golgi
Additional proteolytic cleavages occur to give the mature hormone
The hormone is packaged into secretory granules for later use
What precursor molecule are steroid hormones derived from?
What precursor molecule are amine hormones derived from?
What hormone class includes the thyroid hormones, epinephrine, and norepinephrine?
The amine hormones
Where is thyrotropin-releasing hormone (TRH) produced?
What is the major action of thyrotropin-releasing hormone (TRH)?
Stimulates secretion of TSH and prolactin
Where is corticotropin-releasing hormone (CRH) produced?
What is the major action of corticotropin-releasing hormone (CRH)?
Stimulates secretion of ACTH
Where is gonadotropin-releasing hormone (GnRH) produced?
What is the major action of gonadotropin-releasing hormone (GnRH)?
Stimulates secretion of LH and FSH
Where is growth hormone-releasing hormone (GHRH) produced?
What is the major action of growth hormone-releasing hormone (GHRH)?
Stimulates secretion of growth hormone
Where is somatotropin release-inhibiting hormone (somatostatin; SRIF) produced?
What is the major action of somatotropin release-inhibiting hormone (somatostatin; SRIF)?
Inhibits secretion of growth hormone
Where is prolactin-inhibiting factor (dopamine; PIF) produced?
What is the major action of prolactin-inhibiting factor (dopamine, PIF)?
Inhibits secretion of prolactin
Where is thyroid-stimulating hormone (TSH) produced?
Anterior pituitary
What is the major action of thyroid-stimulating hormone (TSH)?
Stimulates synthesis and secretion of thyroid hormones
Where is follicle-stimulating hormone (FSH) produced?
Anterior pituitary
What is the major action of follicle-stimulating hormone (FSH)?
Stimulates growth of ovarian follicles
Stimulates secretion of estrogen
Where is leutinizing hormone (LH) produced?
Anterior pituitary
What is the major action of leutinizing hormone (LH)?
Stimulates ovulation
Stimulates formation of the corpus luteum
Stimulates ovarian synthesis of estrogen and progesterone
Where is growth hormone (GH) produced?
Anterior pituitary
What is the major action of growth hormone (GH)?
Stimulates protein synthesis and overall growth
Where is prolactin produced?
Anterior pituitary
What is the major action of prolactin?
Stimulates milk production and breast development
Where is adrenocorticotropic hormone (ACTH) produced?
Anterior pituitary
What is the major action of adrenocorticotropic hormone (ACTH)?
Stimulates synthesis and secretion of adrenal cortical hormones
Where is B-lipotropin produced?
Anterior pituitary
What is the major action of B-lipotropin?
Unknown in humans
Where is melanocyte-stimulating hormone (MSH) produced?
Anterior pituitary
What is the major action of melanin-stimulating hormone (MSH)?
Stimulates melanin synthesis
Where is oxytocin produced?
Posterior pituitary
What is the major action of oxytocin?
Milk ejection
Uterine contractions
Where is antidiuretic hormone (vasopressin; ADH) produced?
Posterior pituitary
What is the major action of antidiuretic hormone (vasopressin; ADH)?
Stimulates water reabsorption in the renal collecting ducts
Where are L-thyroxine (T4) and triiodothyronine (T3) produced?
Thyroid gland
What are the major actions of L-thyroxine (T4) and triiodothyronine (T3)?
Stimulates skeletal growth
Increases oxygen consumption
Stimulates heat production
Stimulates protein, fat, and carb utilization
Perinatal maturation of the nervous system
Where are glucocorticoids (cortisol) produced?
Adrenal cortex
What is the major action of glucocorticoids (cortisol)?
Stimulates gluconeogenesis
Where is estradiol produced?
What is the major action of estradiol?
Stimulates growth and development of female reproductive organs
Initiates the follicular phase of the menstrual cycle
Where is progesterone produced?
What is the major action of progesterone?
Initiates the luteal phase of the menstrual cycle
Where is testosterone produced?
What is the major action of testosterone?
Stimulates spermatogenesis
Stimulates the development of male secondary sex characteristics
Where is parathyroid hormone (PTH) produced?
Parathyroid gland
What is the major action of parathyroid hormone?
Increases serum Ca concentration
Decreases serum phosphate concentration
Where is calcitonin produced?
Thyroid gland (parafollicular cells)
What is the major action of calcitonin?
Decreases serum Ca concentration
Where is aldosterone produced?
Adrenal cortex
What is the major action of aldosterone?
Stimulates renal Na reabsorption
Stimulates renal H and K secretion
Where is 1,25-dihydroxycholecalciferol produced?
What is the major action of 1,25-dihydroxycholecalciferol?
Increases Ca absorption in the intestine
Stimulates bone mineralization
Where is insulin produced?
Pancreas (beta cells)
What is the major action of insulin?
Decreases blood glucose concentration
Decreases blood amino acid concentration
Decreases blood fatty acid concentration
Where is glucagon produced?
Pancreas (alpha cells)
What is the major action of glucagon?
Increases blood glucose concentration
Increases blood fatty acid concentration
Where is human chorionic gonadotropin (HCG) produced?
What is the major action of human chorionic gonadotropin (HCG)?
Stimulates estrogen and progesterone synthesis in the corpus luteum
Where is human placental lactogen (HPL) produced?
What is the major action of human placental lactogen (HPL)?
Stimulates estrogen and progesterone synthesis in the corpus luteum
Stimulates protein synthesis and overall growth
How does negative feedback work?
A hormone has biologic actions that inhibit further secretions of that hormone
What type of feedback regulation is most commonly seen in hormone secretion?
Negative feedback
What is the negative feedback loop that terminates insulin secretion?
Increased blood glucose
Insulin is secreted from the pancreatic B cells
This increases glucose uptake by the tissues, and decreases plasma glucose
As blood glucose concentration decreases, further secretion of insulin is inhibited
How does positive feedback work?
This is a rare mechanism, and it both explosive and self-reinforcing
A hormone has biologic actions that cause more secretion of that hormone
What is the positive feedback loop that regulates estrogen secretion?
Estrogen causes LH to be secreted from the anterior pituitary just before ovulation
LH acts on the ovaries and causes estrogen to be secreted?
How do hormones determine the sensitivity of a target tissue?
They regulate the number or sensitivity of receptors
How do inhibitory hormones work?
They decrease the number or affinity of receptors for itself or another hormone
How does progesterone affect hormone sensitivity in the uterus?
It decreases it
It downregulates its own receptor
Also downregulates the estrogen receptor
How do excitatory hormones work?
Increase the number or affinity of receptors for itself or other hormones
How does estrogen affect hormone sensitivity in the ovary?
Estrogen upregulates its own receptor
It also upregulates the LH receptor
What are G proteins?
GTP-binding proteins that couple hormone receptors to effector molecules
Have intrinsic GTPase activity
Three subunits: a, B, and y
The a subunit can bind GTP or GDP
Can be stimulatory (Gs) or inhibitory (Gi)
What second messenger systems are G proteins involved in?
Adenylyl cyclase
What determines the activity of a G protein?
When the a subunit is bound to GDP, the G protein is inactive
When GTP is bound, the G protein is active
The G protein binds GTP and hydrolyzes it to GDP
What mechanism of hormone action does ACTH use?
What mechanism of hormone action does LH use?
What mechanism of hormone action does FSH use?
What mechanism of hormone action does TSH use?
What mechanism of hormone action does ADH use when it binds V2 receptors?
What mechanism of hormone action does HCG use?
What mechanism of hormone action does MSH use?
What mechanism of hormone action does CRH use?
What mechanism of hormone action do B1 and B2 adrenergic receptors use?
What mechanism of hormone action does calcitonin use?
What mechanism of hormone action does PTH use?
What mechanism of hormone action does glucagon use?
What mechanism of hormone action does GnRH use?
What mechanism of hormone action does TRH use?
What mechanism of hormone action does GHRH use?
What mechanism of hormone action does angiotensin II use?
What mechanism of hormone action does ADH use when it binds the V1 receptor?
What mechanism of hormone action does oxytocin use?
What mechanism of hormone action do alpha 1 adrenergic receptors use?
What mechanism of hormone action do glucocorticoids use?
What mechanism of hormone action does estrogen use?
What mechanism of hormone action does testosterone use?
What mechanism of hormone action does progesterone use?
What mechanism of hormone action does aldosterone use?
What mechanism of hormone action does vitamin D use?
What mechanism of hormone action does thyroid hormone use?
What mechanism of hormone action does insulin use?
Activation of a tyrosine kinase
What mechanism of hormone action does IGF1 use?
Activation of a tyrosine kinase
What mechanism of hormone action does ANP use?
What mechanism of hormone action does EDRF use?
What mechanism of hormone action does nitric oxide use?
How does the adenylate cyclase mechanism work?
The hormone binds to a receptor in the membrane
GDP is released from the G protein
GTP replaces it
Adenylate cyclase converts ATP to cAMP
cAMP activates PKA, which phosphorylates various targets
cAMP is degraded to 5'-AMP by phosphodiesterase
What is the relationship between G protein activation and adenylyl cyclase activation?
If the G protein is stimulatory (Gs), AC is activated
If the G protein is inhibitory (Gi), AC is also inhibited
What inhibits phosphodiesterase?
Therefore, phosphodiesterase inhibitors augment the physiologic actions of cAMP
How does the IP3 mechanism work?
The hormone binds to a cell membrane receptor
A G protein activates PLC
PLC liberates IP3 and DAG from membrane phospholipids
IP3 mobilizes Ca from the ER
Ca and DAG activate PKC, which phosphorylates various targets
How does the Ca-calmodulin mechanism work?
A hormone binds to a receptor in the cell membrane
Plasma membrane Ca channels are opened, and Ca is released from the ER
This causes intracellular Ca to increase
Ca binds to calmodulin, and this complex modulates physiologic actions
How does the steroid hormone and thyroid hormone mechanism work?
The hormone diffuses across the membrane and binds to its receptor
The hormone-receptor complex translocates to the nucleus and dimerizes
These dimers act as transcription factors, and they bind to steroid-responsive elements (SREs) in DNA to initiate transcription
New mRNA is produced and is eventually translated into protein
What connects the hypothalamus to the anterior pituitary?
The hypothalamic-hypophysial portal system
Blood from the hypothalamus (containing high concentrations of hypothalamic organs) is delivered to the anterior pituitary
Those hypothalamic hormones stimulate or inhibit the release of anterior pituitary hormones
What is the organization of the posterior pituitary?
Derived from neural tissue
Nerve cell bodies are found in the hypothalamic nuclei
Posterior pituitary hormones are synthesized in the nerve cell bodies, packaged into secretory granules, and transported down the axons to the posterior pituitary for circulatory release
What are the hormones produced by the anterior pituitary?
What hormones are glycoprotein hormones?
What are the main features of glycoprotein hormones?
Each hormone has an alpha and a beta subunit
The alpha subunit is the same for all
The beta subunits are different, and are responsible for the unique biological activities of each hormone
What are the products of POMC processing?
POMC (pro-opiomelanocortin)
Gives rise to ACTH, melanocyte-stimulating hormone (MSH), B-lipotropin, and B-endorphin
Where are a-MSH and B-MSH produced?
The intermediary lobe
This is a rudimentary structure in adult humans
What is the hormone that determines normal growth to adult size?
Growth hormone (somatotropin)
What is the structure of growth hormone?
Single-chain polypeptide
Homology to prolactin (also to human placental lactogen)
What type of secretion characterizes GH production?
Pulsatile secretion
What environmental factors stimulate GH production?
Hormones related to puberty
What environmental factors inhibit GH production?
How does the hypothalamus control GH secretion?
GHRH stimulates synthesis and secretion of GH
Somatostatin inhibits GH secretion by blocking GHRH response
What is the GH negative feedback loop that is mediated by somatomedins?
Somatomedins are produced by GH-stimulated target organs
They inhibit GH secretion from the anterior pituitary
They also stimulate hypothalamic somatostatin secretion
What is the GH negative feedback loop that is mediated by GHRH and GH?
GHRH inhibits its own hypothalamic secretion
GH inhibits its own pituitary secretion
GH stimulates hypothalamic somatostatin secretion
What are the actions of GH in the liver?
Somatomedins (IGF) are produced
IGF serves as the intermediary of several physiologic actions
What type of receptor is the IGF receptor?
Receptor tyrosine kinase (similar to insulin receptor)
What are the two types of physiologic effects mediated by GH?
Direct effects
IGF effects (GH --> IGH production in the liver)
What are the direct effects of GH?
Decreased glucose uptake (diabetogenic)
Increased lipolysis
Increased protein synthesis
Increased lean body mass
Increased IGF production
What are the IGF-mediated effects of GH?
Increased protein synthesis in chondrocytes
Increased linear growth (pubertal growth spurt)
Increased protein synthesis in muscle
Increased lean body mass
Increased protein synthesis
Increased organ size
What are the symptoms of GH deficiency in children?
Failure to grow
Short stature
Mild obesity
Delayed puberty
What are some causes for GH deficiency?
Lack of GH
Hypothalamic dysfunction -- decreased GHRH release
Failure to generate IGF in the liver
GH receptor deficiency
How would you treat GH excess?
Somatostatin analogs such as octreotide
This will inhibit GH secretion
What are the symptoms of GH excess?
Before puberty: increased linear growth (gigantism)
After puberty: periosteal bone growth, increased organ size, glucose intolerance
What is the hormone responsible for lactogenesis?
What hormone acts in conjunction with estrogen to promote breast development?
What hormone is prolactin structurally homologous to?
How is prolactin secretion regulated?
PIF (dopamine) is produced by the hypothalamus, and this inhibits prolactin secretion
TRH stimulates prolactin secretion
Prolactin inhibits its own secretion by stimulating PIF secretion
What would happen to prolactin secretion if you disrupted the hypothalamo-hypophysial tract?
You would have increased and sustained lactation
This is because you would no longer be delivering inhibitory PIF
What are the actions of prolactin?
Milk production in the breast
Breast development (in conjunction with estrogen)
Inhibition of ovulation (by decreasing GnRH)
Inhibition of spermatogenesis (by decreasing GnRH)
What is a symptom of prolactin deficiency?
Failure to lactate
What are the symptoms of prolactin excess?
Galactorrhea (spontaneous lactation that is not associated with pregnancy)
Decreased libido
Failure to ovulate
Amenorrhea (inhibition of GnRH secretion)
What might cause prolactin excess?
Hypothalamic destruction, resulting in loss of PIF
Prolactinomas (prolactin-secreting tumors)
How would you treat prolactin excess?
Bromocriptine -- acts as a dopamine/PIF agonist and reduces secretion
What are the hormones of the posterior pituitary?
How are the posterior pituitary hormones made?
They are synthesized in hypothalamic nuclei and packaged into secretory granules with their respective neurophysins
Travel down the nerve axons for secretion by the posterior pituitary
Where is ADH produced?
The supraoptic nuclei of the hypothalamus
What does ADH do?
Increases water permeability of the late distal tubule and collecting ducts
What factors increase ADH secretion?
Increased serum osmolarity
Volume depletion
Nicotine, opiates, antineoplastic drugs
What factors decrease ADH secretion?
Decreased serum osmolarity
alpha-adrenergic agonists
What are the actions of ADH?
Increases water permeability of the principal cells of the late distal tubule and CD via V2 receptors (cAMP mechanism)
Constriction of vascular smooth muscle via V1 receptors (IP3/Ca mechanism)
Where in the hypothalamus does oxytocin originate?
The paraventricular nuclei
What does oxytocin do?
Causes ejection of milk from the breast when stimulated by suckling
How does suckling regulate oxytocin secretion?
This is the major stimulus for secretion
Afferent fibers carry impulses from the nipple to the spine
Relays in the hypothalamus trigger secretion from the posterior pituitary
The sight or sound of the infant can stimulate secretion even in the absence of suckling
How do dilation of the cervix and orgasm regulate oxytocin production?
They both stimulate secretion
How does oxytocin induce milk ejection?
It causes the myoepithelial cells to contract
Milk is forced from the mammary alveoli into the ducts
How does oxytocin induce uterine contractions?
During pregnancy, oxytocin receptors in the uterus are upregulated as birth approaches
What hormone stimulates the synthesis of thyroid hormone?
How are thyroid hormones produced?
Thyroglobulin is synthesized from tyrosine in the thyroid follicular cells
It is then packaged into secretory vesicles and exocytosed into the follicular lumen
Iodide is transported into the follicular cells and oxidized to iodine
Tyrosine residues of thyroglobulin react with I2 to form monoiodotyrosine (MIT) and diiodotyrosine (DIT)
Two molecules of DIT combine to form thyroxine (T4)
One molecule each of DIT and MIT combine to form triiodothyronine (T3)
Iodinated thyroglobulin is stored as colloid in the follicular lumen until needed
When the cells are stimulated by TSH, colloid is endocytosed into the follicular cells
Lysosomal enzymes digest thyroglobulin to release T3 and T4 into circulation
Leftover MIT and DIT are deiodinated and the iodine is recycled
In the circulation, T3 and T4 is usually bound to thyroxine-binding globulin (TBG)
During thyroid hormone synthesis, how is iodide transported into the cell?
I pump or Na-I cotransport
These transporters actively transport iodine into the cell
Inhibited by thiocynate and perchlorate anions
What enzyme catalyzes the oxidation of I- during thyroid hormone synthesis?
Peroxidase (associated with the cell membrane)
Inhibited by propylthiouracil
How do you treat hyperthyroidism?
This will inhibit the oxidation of iodide to iodine during thyroid hormone synthesis
What is the Wolff-Chaikoff effect?
High levels of iodide will inhibit the formation of MIT and DIT
What are the relative quantities and activities of synthesized T3 and T4?
T4 is more abundant
T3 is more active
What enzyme deiodinates MIT and DIT to recycle iodine?
Thyroid deiodinase
Why does deficiency of thyroid deiodinase mimic I2 deficiency?
In both cases, you are unable to synthesize new MIT and DIT because there isn't enough iodine available
What happens to TBG levels during hepatic failure?
TBG levels rise
This leads to a decrease in total thyroid hormone levels, but normal levels of free hormone
What happens to T4 in peripheral tissues?
It is converted to T3 by 5'-iodinase
It can also be converted to inactive reverse T3 (rT3)
What is the pathway that stimulates thyroid hormone production?
TRH from the hypothalamus stimulates TSH secretion in the anterior pituitary
TSH stimulates synthesis and secretion in the thyroid via the cAMP mechanism
What is the primary symptom of chronic TSH elevation?
Hypertrophy of the thyroid gland
What is the negative feedback loop for thyroid hormone?
T3 downregulates TRH receptors in the anterior pituitary, which inhibits TSH secretion
What are thyroid-stimulating immunoglobulins?
IgG molecules that bind to TSH receptors on the thyroid
Stimulate synthesis of T3 and T4
High concentrations found in patients with Graves' disease
How much more potent is T3 than T4?
3x more potent
What are the effects of thyroid hormone upon growth?
Required for attainment of adult stature
Promote bone formation in conjunction with somatomedins
Stimulate bone maturation
In a patient with thyroid deficiency, how does bone age compare to chronologic age?
Bone age is less than it should be
This is because thyroid hormone is required for bone maturation
What are the effects of thyroid hormone upon the CNS during the perinatal period?
Required for CNS maturation
Deficiency causes irreversible mental retardation
How can neonatal hypothyroidism-associated mental retardation be avoided?
Hormone replacement therapy
There is only a narrow window when this is effective, so screening for neonatal hypothyroidism is both necessary and mandatory
What are the effects of hyperthyroidism upon the CNS in the adult?
What are the effects of hypothyroidism upon the CNS in the adult?
Slowed speech
Impaired memory
Decreased mental capacity
Why are beta blockers such as propanolol good adjunct treatments for hyperthyroidism?
Thyroid hormone upregulates B1 adrenergic receptors in the heart
This basically makes you overly sensitive to sympathetic stimulation
Beta blockers prevent this
What are the effects of thyroid hormone upon basal metabolism rate?
O2 consumption and BMR are increased in all tissues except the brain, gonads, and spleen
This increases heat production
What are the metabolic effects of thyroid hormone?
Overall, metabolism increases
Glucose absorption in the GI tract increases
Glycogenolysis increases
Gluconeogenesis increases
Glucose oxidation increases
Lipolysis increased
Protein synthesis AND degradation are increased
What is the overall effect of thyroid hormone upon protein metabolism?
Overall, it is catabolic (although protein synthesis does increase -- degradation increases more)
What are the three zones of the adrenal cortex?
Zona glomerulosa
Zona fasciculata
Zona reticularis
What hormone is produced by the zona glomerulosa?
What are the effects of thyroid hormone upon the autonomic nervous system?
Has many of the same actions as sympathetic neurotransmitters because it upregulates B1 adrenergic receptors in the heart
What is the effect of thyroid hormone upon the Na-K ATPase?
It upregulates it; this is why oxygen consumption is also increased
What are the effects of thyroid hormone upon the cardiovascular and respiratory systems?
Heart rate and stroke volume increase, resulting in increased cardiac output
Ventilation rate increases
What hormones are produced by the zona fasciculata?
Glucocorticoids (cortisol)
What hormones are produced by the zona reticularis?
Androgens (dehydroepiandrosterone and androstenedione)
What are the 21-carbon steroid hormones?
Progesterone -- the precursor for the rest
How is progesterone modified to make deoxycorticosterone?
Hydroxylation at C21
Note that deoxycorticosterone has mineralocorticoid activity, not glucocorticoid
How is progesterone modified to make glucocorticoids?
Hydroxylation at C17
Note that there is a pregnenolone intermediate
How is pregnenolone modified to give androgens?
Cleavage of the C20,21 side chain
This gives a 19C steroid hormone (dehydroepiandrosterone or androstenedione)
Where does the conversion of pregnenolone to androgens take place?
Adrenal cortex
How are adrenal androgens excreted?
Lost as 17-ketosteroids in the urine
How do the testes produce testosterone?
They convert androstenedione (from the adrenal cortex) to testosterone
What major family of hormones does aldosterone belong to?
What are the 18C steroid hormones?
The estrogens
How are estrogens produced?
The A ring of testosterone is oxidized (aromatization)
This occurs in the ovaries and placenta, but not in the adrenal cortex or testes
How does glucocorticoid secretion vary throughout the day?
Oscillates with a 24 hour periodicity (circadian rhythm)
Cortisol levels are highest just before waking, and lowest in the evening
What hormones stimulate the secretion of glucocorticoids?
CRH (from the hypothalamus)
ACTH (from the anterior pituitary)
How does CRH stimulate glucocorticoid secretion?
CRH-containing neurons in the paraventricular nuclei are stimulated, and CRH is delivered to the anterior pituitary
CRH binds to receptors on corticotrophs
cAMP signaling cascade
POMC is synthesized (ACTH precursor)
ACTH is secreted
How does ACTH stimulate glucocorticoid secretion?
Increases steroid hormone synthesis in all zones of the adrenal cortex by stimulating cholesterol desmolase (which produces pregnenolone)
Upregulates its own receptor on the adrenal cortex to increase ACTH sensitivity
cAMP mechanism
What can cause adrenal cortex hypertrophy?
Overstimulation with ACTH (overproduction of steroid hormones)
What is the negative feedback loop for cortisol?
Cortisol inhibits CRH secretion from the hypothalamus
Also inhibits ACTH secretion from the anterior pituitary
How does the dexamethasone suppression test work?
Dexamethasone is a synthetic glucocorticoid that inhibits ACTH secretion
It is used to determine the extent to which you can inhibit cortisol secretion
How do people with ACTH-secreting tumors of the anterior pituitary respond to the dexamethasone suppression test?
Low doses have no effect
High doses inhibit cortisol secretion
This is because you are reducing the stimulus (ACTH) for cortisol production
How do people with adrenal cortical tumors respond to the dexamethasone suppression test?
Not even a high dose inhibits cortisol secretion
This is because the cells have lost responsiveness to ACTH and just churn out cortisol
How is aldosterone secretion regulated?
Tonic control is mediated by ACTH
Also affected by the renin-angiotensin system and serum potassium
How does the renin-angiotensin system cause aldosterone to be secreted?
Decreased blood volume causes renal perfusion pressure to decrease
Renin is secreted and cleaves angiotensinogen to angiotensin I
Angiotensin I is converted to angiotensin II by ACE
Angiotensin II acts on the zona glomerulosa of the adrenal cortex to cause corticosterone to be metabolized to aldosterone
Aldosterone increases renal Na absorption
How does hyperkalemia impact aldosterone secretion?
Hyperkalemia increases aldosterone secretion
Aldosterone promotes K excretion, which restores plasma K to normal
What family of hormones is primarily responsible for response to stress?
How do glucocorticoids stimulate gluconeogenesis?
Increase protein catabolism in the muscle
Decrease protein synthesis (these two things provide amino acids for gluconeogenesis)
Decrease glycolysis
Decrease insulin sensitivity of adipose tissue
Increase lipolysis, which provides glycerol to the liver for gluconeogenesis
How do glucocorticoids mediate anti-inflammatory effects?
Induce lipocortin synthesis, which inhibits phospholipase A2
Recall that PLA2 liberates arachidonic acid, a precursor for prostaglandins and leukotrienes, from membrane phospholipids
They also inhibit histamine and serotonin degranulation in mast cells and platelets
How do glucocorticoids suppress the immune system?
Inhibit the production of IL2
Inhibit T cell proliferation
These are both important in cellular (T cell-mediated) immunity
Why are glucocorticoids used to prevent organ rejection?
They suppress cellular immunity
How do glucocorticoids contribute to the maintenance of vascular response to catecholamines?
Cortisol upregulates alpha1 adrenergic receptors on arterioles
This increases their sensitivity to norepinephrine
What are the cardiovascular effects of cortisol excess and deficiency?
Excess -- hypertension
Deficiency -- hypotension
This is because cortisol upregulates alpha 1 receptors on arterioles, which sensitizes them to norepinephrine
What are the effects of aldosterone on electrolyte transport in the nephron?
Increased Na reabsorption
Increased K and H secretion
These changes occur in the late distal tubule and CD
What is Addison's disease?
Primary adrenocortical insufficiency
Usually caused by autoimmune distruction of the adrenal cortex, results in adrenal crisis
What are the symptoms of primary adrenocortical deficiency?
Decreased adrenal glucocorticoids, androgens, and mineralocorticoids
Increased ACTH because of lost negative feedback loop
Hypoglycemia from cortisol deficiency
Weight loss, nausea, vomiting, weakness
Decreased pubic and axillary hair in women because of decreased adrenal androgens
ECF volume contraction, hypotension, hyperkalemia, and metabolic acidosis because of aldosterone deficiency
What is the mechanism for hyperpigmentation in Addison's disease?
Low cortisol levels stimulate ACTH
ACTH contains the MSH fragment
Melanin production is stimulated
What is the difference between primary and secondary adrenocortical deficiency?
Primary -- general destruction of the adrenal cortex
Secondary -- loss of ACTH secretion from the anterior pituitary
How do the symptoms of secondary adrenocortical deficiency differ from those of Addison's disease?
No hyperpigmentation (because there is no ACTH)
No volume contraction, hyperkalemia, or metabolic acidosis (because aldosterone is normal)
What is Cushing's disease?
A type of adrenocortical excess that is caused by ACTH overproduction
Usually caused by the clinical administration of glucocorticoids
What causes adrenocortical excess?
Administration of pharmacologic doses of glucocorticoids
Primary hyperplasia of the adrenal glands
What are the symptoms of adrenocortical excess?
Increased cortisol and androgen levels
Decreased ACTH (if caused by adrenal hyperplasia or exogenous glucocorticoids)
Increased ACTH (if caused by ACTH overproduction)
Hyperglycemia from elevated cortisol
Increased protein catabolism and muscle wasting
Central obesity
Poor wound healing
Virilization of women from elevated adrenal androgens
Hypertension from elevated cortisol and aldosterone
Osteoporosis from elevated cortisol (bone resorption)
How would you treat Cushing's disease?
This inhibits steroid hormone synthesis
What is Conn's syndrome?
Caused by aldosterone-secreting tumors
What are the symptoms of Conn's syndrome?
Hypertension (Na reabsorption)
Hypokalemia (K secretion)
Metabolic alkalosis (H secretion)
Decreased renin secretion because of increased ECFV and hypertension)
What is 21B-hydroxylase deficiency?
The most common abnormality of the steroidogenic pathway
Belongs to a group of disorders that constitute adrenogenital syndrome
What are the symptoms of 21B-hydroxylase deficiency?
Decreased cortisol and aldosterone (because their precursor can't be synthesized)
Accumulation of 17-hydroxyprogesterone and progesterone (because they can't be metabolized)
Increased ACTH (because of decreased feedback inhibition by cortisol)
Adrenocortical hyperplasia
Increased adrenal androgens (because 17-hydroxyprogesterone accumulates)
Increased urinary 17-ketosteroids
Virilization in women
Early linear growth and appearance of pubic/axillary hair
Suppression of gonadal function in men and women
What are the symptoms of 17a-hydroxylase deficiency?
Decreased androgens and glucocorticoids
Increased mineralocorticoids (because precursor accumulates)
Lack of pubic and axillary hair in women due to lack to androgens
Hypoglycemia from glucocorticoid deficiency
Metabolic alkalosis, hypokalemia, and hypertension because of excess aldosterone
Increased ACTH because of decreased cortisol
How is the endocrine pancreas organized?
Islets of Langerhans
Contains alpha, beta, and delta cells
Gap junctions link each cell type to itself, as well as to each other for rapid communication
Portal blood supply allows insulin-containing blood from the beta cells to bath alpha and delta cells
How does insulin affect K transport?
Insulin causes K to be taken up into cells, producing hypokalemia
What are the major effects of glucagon?
Increased glycogenolysis
Decreased glycogen synthesis
Increased gluconeogenesis
Ketoacid production -- acetoacetate and BHB are produced from acetyl CoA
How is glucagon secretion regulated?
Glucagon is secreted in response to decreased blood glucose
What tissues does glucagon act upon?
Adipose tissue
How does glucagon inhibit glycolysis?
It decreases the production of fructose 2,6-bisphosphate
This decreases PFK activity
What is the effect of glucagon upon urea production?
Amino acids are consumed as gluconeogenesis increases
The resulting amino groups are incorporated into urea
Urea production increases
How are the endocrine cells of the pancreas organized within the pancreas?
Beta cells -- center of the islet
Alpha cells -- periphery of the islet
Delta cells -- scattered throughout
What are the secretory products of the three cell types of the endocrine pancreas?
Alpha cells -- glucagon
Beta cells -- insulin
Delta cells -- somatostatin and gastrin
What is the structure of insulin?
Contains an A and a B chain
Chains are joined by two disulfide bonds
How is insulin processed?
Proinsulin is synthesized as a single polypeptide chain
In the storage granules, the connecting (C) peptide is cleaved by proteases to give mature insulin
What is the clinical relevance of C peptide?
Used to monitor beta cell function in diabetic patients on insulin therapy
How is insulin secretion regulated?
Blood glucose concentration is the primary regulator
Increased blood glucose stimulates insulin secretion
An initial burst is followed by sustained secretion
What is the mechanism of insulin secretion?
Glucose binds to GLUT2 on pancreatic beta cells
Glucose enters the cell and is oxidized to ATP
ATP closes K channels in the plasma membrane
The beta cells depolarize
Depolarization opens Ca channels
Intracellular Ca concentration increases
Insulin granules exocytose
How do sulfonylurea drugs work?
Similar to ATP, these drugs close ATP-gated K channels
This causes pancreatic beta cells to depolarize
Ca influx triggers insulin exocytosis
What is the structure of the insulin receptor?
Tetramer with two alpha subunits and two beta subunits
The beta subunits span the cell membrane and have tyrosine kinase activity
When insulin binds, the tyrosine kinases autophosphorylate the beta subunits
The phosphorylated receptor then phosphorylates intracellular proteins
Insulin-receptor complexes enter the target cells; insulin therefore down-regulates its own receptor in target tissues
What are the tissues targeted by insulin?
Skeletal muscle
Adipose tissue
How does insulin decrease blood glucose concentration?
Increases glucose uptake into target cells by mediating the insertion of glucose transporters into the cell membrane
Promotes formation of glycogen in the muscle and liver
Decreases gluconeogenesis by increasing the production of fructose 2,6-bisphosphate, which stimulates PFK
How does insulin decrease blood fatty acid and ketoacid concentrations?
Stimulates TAG synthesis
Inhibits lipolysis
Inhibits ketoacid formation because less acetyl CoA from fatty acid degradation is available
How does insulin decrease blood amino acid concentration?
Stimulates amino acid uptake into cells
Increases protein synthesis
Decreases protein degradation
Therefore, insulin is anabolic
How does insulin cause hypokalemia?
Increases K uptake into cells
How could diabetes produce hypotension?
Hyperglycemia causes the blood glucose concentration to exceed the Tm of the kidney
Unabsorbed glucose acts as an osmotic diuretic in the urine
Causes excess water to be lost in the urine, resulting in ECF volume contraction
How could diabetes produce metabolic acidosis?
Overproduction of ketoacids
Patients will increase their ventilation rate in order to compensate
What does somatostatin do?
Inhibits the secretion of insulin, glucagon, and gastrin
How is Ca transported in the blood?
40% is bound to plasma proteins
60% is unbound and is ultrafilterable
What does it mean for Ca to be ultrafilterable?
Includes Ca that is complexed to anions such as phosphate, as well as free, ionized Ca
Is free ionized Ca biologically active?
What factors determine the overall serum Ca concentration?
Intestinal absorption
Renal excretion
Bone remodeling
How is Ca balance maintained?
Net intestinal absorption must be balanced by urinary excretion
Under what conditions is a positive Ca balance observed?
Seen in growing children
Intestinal absorption exceeds urinary excretion, and the excess is deposited in growing bones
Under what conditions is a negative Ca balance observed?
Pregnancy and lactation
Urinary excretion exceeds intestinal absorption, and the deficit comes from maternal bones
What hormone is involved in the regulation of serum Ca?
Where is PTH produced?
Synthesized and secreted by the chief cells of the parathyroid glands
What causes PTH to be secreted?
Decreased serum Ca
Mildly increased serum Mg (note that greatly increased Mg will inhibit PTH secretion and produce symptoms of hypocalcemia)
What are the major functions of PTH?
Increase serum Ca
Decrease serum phosphate
How does PTH increase serum Ca?
Increases bone resorption -- brings Ca and phosphate into the ECF
Inhibits renal phosphate absorption in the proximal tubule
Increases renal Ca reabsorption in the distal tubule
Increases intestinal Ca absorption by stimulating production of vitamin D3 in the kidney
What is an indicator bone resorption?
Increased hydroxyproline secretion
What is the phosphaturic effect?
PTH inhibits phosphate reabsorption in the renal proximal tubule, effectively increasing phosphate excretion
Urinary cAMP is also excreted
What is the most common cause of primary hyperparathyroidism?
Parathyroid adenoma
What are the symptoms of primary hyperparathyroidism?
Increased phosphate excretion
Increased urinary Ca excretion (because of the increased filtered Ca load)
Increased urinary cAMP
Bone resorption
What causes humor hypercalcemia of malignancy?
PTH-related peptide (PTH-rp) is secreted by some malignant tumors
PTH-rp has all of the physiological actions of PTH
What are the symptoms of humor hypercalcemia of malignancy?
Increased urinary phosphate excretion
Decreased serum PTH levels due to feedback inhibition from high serum Ca
What are some causes of hypoparathyroidism?
Thyroid surgery
What are some symptoms of hypoparathyroidism?
Decreased urinary phosphate excretion
What is Albright's hereditary osteodystrophy?
Also known as pseudohypoparathyroidism type 1a
Defective Gs protein in the kidney and bone, which causes end-organ resistance to PTH
Hypocalcemia and hyperphosphatemia are observed, and they are not correctable by administration of exogenous PTH
Circulating PTH levels are increased (stimulated by hypocalcemia)
How does chronic renal failure impact Ca and phosphate homeostasis?
Decreased GFR leads to increased serum phosphate
Serum phosphate complexes with Ca and decreases free ionized Ca
The diseased renal tissue produces less 1,25-dehydroxycholecalciferol, which contributes to the decreased plasma Ca
What is renal osteodystrophy?
Increased PTH
Decreased vitamin D3
This causes increased bone resorption and osteomalacia
What role does vitamin D play in bone mineralization?
Provides Ca and phosphate to the ECF for bone mineralization
What diseases does vitamin D deficiency cause?
Rickets (children)
Osteomalacia (adults)
How is vitamin D synthesized?
The active form is 1,25-dihydroxycholecalciferol
It is produced in the kidney by 1a-hydroxylase
How does vitamin D affect Ca and phosphate homeostasis?
Increases intestinal Ca absorption
Increases intestinal phosphate absorption
Increases renal reabsorption of Ca and phosphate
Increases bone resorption
What stimulates calcitonin production?
Increased serum Ca
What does calcitonin do?
Inhibits bone resorption
How is calcitonin used clinically?
Used to treat hypercalcemia
What determines genetic sex?
Sex chromosomes
Males are XY
Females are XX
What determines gonadal sex?
The presence of testes in males and ovaries in females
What determines phenotypic sex?
The characteristics of the internal genital tract and external genitalia
What dictates development of the male phenotype?
Testes secrete antimullerian hormone and testosterone
Testosterone stimulates the growth and differentiation of the Wolffian ducts, which develop into the male internal genital tract
Antimullerian hormone causes the mullerian ducts to atrophy (they would have become the female internal genital tract)
What dictates development of the female phenotype?
The ovaries secrete estrogen
Since there is no testosterone, the wolffian ducts do not differentiate into the male genital tract
Since there is no antimullerian hormone, the mullerian ducts aren't suppressed and develop into the female internal genital tract
What cells produce testosterone?
Leydig cells
How does LH stimulate testosterone synthesis?
It stimulates cholesterol desmolase, the first step in the testosterone biosynthetic pathway
How do accessory sex organs synthesize DHT?
They contain 5a-reductase
This converts testosterone to its active form, DHT
How would you pharmacologically treat benign prostatic hyperplasia?
5a-reductase inhibitors (finasteride)
This blocks the activation of testosterone to DHT
What regulates the secretion of FSH and LH?
GnRH from the hypothalamus
What does FSH do in men?
Acts on the Sertoli cells to maintain spermatogenesis
How do the Sertoli cells inhibit FSH secretion?
After being stimulated by FSH, they produce inhibin, which inhibits further FSH secretion
What does LH do in men?
Acts on the Leydig cells to promote testosterone synthesis
Testosterone reinforces the spermatogenic effects of FSH in the Sertoli cells
How does testosterone inhibit LH secretion?
Directly inhibits LH secretion from the anterior pituitary
Inhibits the release of GnRH from the hypothalamus
What are the actions of testosterone?
Differentiation of the epididymis, vas deferens, and seminal vesicles
Pubertal growth spurt and its cessation
Deepening of voice
Increased muscle mass
Growth of the penis and seminal vesicles
What are the actions of DHT?
Differentiation of penis, scrotum, and prostate
Male hair pattern
Male pattern baldness
Sebaceous gland activity
Growth of prostate
What causes androgen insensitivity syndrome?
Aka testicular feminizing syndrome
Caused by a deficiency of androgen receptor in target tissues
Testosterone and DHT actions are absent
What are the symptoms of androgen insensitivity syndrome?
Female external genitalia
No internal genital tract
Elevated testosterone levels due to lack of receptors (lack of feedback inhibition)
What happens during puberty in terms of hormone production?
Puberty is initiated by the onset of pulsatile GnRH secretion from the hypothalamus
FSH and LH are secreted in a pulsatile fashion
GnRH upregulates its own receptor in the anterior pituitary
Where are androgens produced in females?
Theca cells produce testosterone (stimulated by LH)
Testosterone diffuses to the granulosa cells, which contain aromatase and convert testosterone to estradiol (stimulated by FSH)
What are the effects of FSH and LH upon the ovaries?
Steroidogenesis in the ovarian follicle and corpus luteum
Follicular development beyond the antral stage
What are the actions of estrogen?
Negative and positive feedback on FSH and LH secretion
Maturation and maintenance of the fallopian tubes, uterus, cervix, and vagina
Development of female secondary sex characteristics
Breast development
Upregulates estrogen, LH, and progesterone receptors
Proliferation and development of ovarian granulosa cells
Maintains pregnancy
Lowers the uterine threshold to contractile stimuli during pregnancy
Stimulates prolactin secretion (but blocks its action on the breast)
What are the actions of progesterone?
Negative feedback effects upon FSH and LH secretion during the luteal phase
Maintains secretory activity of the uterus during the luteal phase
Maintains pregnancy
Raises the uterine threshold to contractile stimuli during pregnancy
Breast development
What are the phases of the menstrual cycle?
Follicular phase (days 0-14)
Ovulation (day 14)
Luteal phase (days 14-28)
Menses (days 0-4)
What happens during the follicular phase of the menstrual cycle?
A primordial follicle develops, with atresia of neighboring follicles
LH and FSH receptors are upregulated in the theca and granulosa cells
Estradiol increases and causes proliferation of the uterus
FSH and LH are suppressed by the negative feedback effect of estradione
Progesterone is low
What happens during ovulation in the menstrual cycle?
Occurs 14 days before menses, regardless of cycle length
A burst of estradiol at the end of the follicular phase has a positive feedback effect on the secretion of FSH and LH (LH surge)
Ovulation occurs as a result of the LH surge
Estrogen levels decrease just after ovulation
Cervical mucous increases in quantity, and becomes less viscous (more penetrable by sperm)
What happens during the luteal phase of the menstrual cycle?
The corpus luteum begins to develop, and it produces estrogen and progesterone
The vascularity and secretory activity of the endometrium increase to prepare for a fertilized egg
Basal body temperature increases
If fertilization does not occur, the corpus luteum regresses at the end of the luteal phase, and estrogen and progesterone levels decrease
What happens during menses?
The endometrium is sloughed off because of the abrupt withdrawal of estradiol and progesterone
What happens to estrogen and progesterone levels during pregnancy?
They steadily increase
This maintains the endometrium for the fetus, suppresses ovarian follicular function, and stimulates breast development
What does human chorionic gonadotropin do?
It rescues the corpus luteum from regression
It is produced by the placenta in response to fertilization
What hormonal changes occur during the first trimester?
The corpus luteum produces estradiol and progesterone
HCG peaks at week 9 and then declines
What hormone changes occur during the second and third trimester?
The placenta produces progesterone
The fetal adrenal gland and placenta produce estrogens
The major placental estrogen is estriol
Human placental lactogen is produced throughout the pregnancy, and its actions are similar to GH and prolactin
What happens during parturition?
Throughout pregnancy, progesterone increases the threshold for uterine contraction
Near term, the estrogen/progesterone ratio increases, which makes the uterus more sensitive to contractile stimuli
The initiating event in parturition is unknown
What happens to prolactin levels during pregnancy?
They steadily increase because estrogen stimulates prolactin secretion
Why doesn't lactation occur during pregnancy?
Estrogen and progesterone block the action of prolactin on the breast
After parturition, estrogen and progesterone levels decrease and lactation begins
How does suckling affect lactation?
It stimulates both oxytocin and prolactin secretion
This maintains lactation
How does lactation suppress ovulation?
Prolactin continues to be produced, and has the following effects:
Inhibits GnRH secretion
Inhibits the action of GnRH on the anterior pituitary, so LH and FSH secretion are antagonized
Inhibits LH and FSH from acting on the ovaries