Endocrinology Flashcards
chemical substance that is produced and secreted into the blood by an organ or tissue and that has a specific effect on a target tissue located away from the site of its origin.
Hormone*
Prostaglandins?
-influences neighboring cells
-autocrine and paracrine function
-very short half-life
Exocrine or endocrine gland?
Secretory products are
released on to “external surfaces”
* e.g. Sweat, Salivary gland
Exocrine gland
Exocrine or endocrine gland?
-Secretory products into the “blood stream”
-transport them to specific target tissues
Endocrine gland
-Upon reaching the specific target
* Secretary product alters the function of target
cell
❖ Characteristics of endocrine hormones and their effects:
Effects are not on and off but graded…
up or down
❖ Characteristics of endocrine hormones and their effects:
Secretion is not constant but usually occurs in _______.
pulses
-Provocative tests are required (stimulates max release)
❖ Characteristics of endocrine hormones and their effects:
Effects of the hormones continue after…
the hormone is gone
❖ Characteristics of endocrine hormones and their effects:
Hormones don’t act alone. What are some examples?
blood glucose; insulin and glucagon
❖ Characteristics of endocrine hormones and their effects:
Some hormones do similar things at….
different rates
Glucagon & cortisol: increases [glucose]blood, glucagon: rapid & temporary v. cortisol: slow & sustained
❖ Characteristics of endocrine hormones and their effects:
Some hormones accomplish similar results with different…
tissue specificities
-Epi & glucagon on glycogenolysis. Epi: muscle v. Glucagon: best on liver
❖ Characteristics of endocrine hormones and their effects:
Sometimes the tissue determines the _________ of the response.
quality
ex: EPI- glycogenolysis in muscle( increases glucose) & lipolysis in adipose (increases FA)
❖ Characteristics of endocrine hormones and their effects:
Hormone don’t always fit the ________ definition.
classical
ex: e.g. ACTH (mostly released in the adrenal glands but also in the brain)
What are the physiologic functions of hormones?
-Maintenance of
internal milieu
-Production
-Growth and
Development
-Energy Metabolism
How many amino acids are peptides? Proteins?
peptides = <100
proteins = >100
Where does ADH come from?
hypothalamus
Hormone type:
-Water soluble and do not require transport proteins
-short half-life
-synthesized from amino acids
➢Protein /Peptide Hormones
e.g. insulin, glucagon
Hormone type:
Synthesized from cholesterol
* Lipid soluble and require transport proteins
– Only free-form is biologically-active
* Long half life
Steroid hormones
e.g. testosterone, aldosterone
Hormone type:
derived from tyrosine
Amino acid-based hormones
e.g. Thyroxine, epinephrine (catecholamine)
_____________ stimulates transcription of sodium/potassium ATPase
aldosterone
What causes hormones to have different mechanisms of action?
due to structural and solubility differences.
-large & H2O soluble
➡ tend to remain in the circulation
✴These hormones bind to EXTRACELLULAR RECEPTORS activating a protein cascade
➢ Involves membrane receptor activation & a secondary messenger
Protein-based hormones
Cross membranes –> bind DIRECTLY to their intracellular targets.
✴ Hormone-Receptor complex DIRECTLY activates TRANSCRIPTION.
Steroid hormones: lipophilic
❖ Hormone secretion occurs in _______ or ________ rather than in a continuous,
constant manner
bursts, pulses
Only a small portion of the hormone is removed by the target tissue;
most are cleared by
the liver or kidneys
__________ hormones: actions are specific for another endocrine gland
Tropic
___________ hormones: Directly stimulate target cells to induce
effects.
❖ Non-tropic
__________ hormone: Works on organ or tissues to enhance cellular “growth, differentiation & survival”
Trophic
(bigger word, bigger tissues)
Major function of the anterior pituitary? posterior pituitary?
anterior pituitary- makes hormones
posterior pituitary- storage of hypothalamus hormones.
The hypothalamus is Connected to pituitary via a cluster of nerves & blood vessels called the pituitary _______
stalk
The hypothalamus produces what factors?
releasing factors
(RF) & inhibiting factors (IF).
What is PVN?
paraventricular nucleus
What is SON?
supraoptic nucleus
Composed of nests of different cell types that secrete different hormones
– Hormone secretion is controlled by the hypothalamus (Tropic hormones)
Adenohypophysis (anterior lobe)
Adenohypophysis (anterior lobe):
– Hormones: FLAT PEG?
FSH, LH, ACTH, TSH
Prolactin, Endorphins, GH
Does NOT synthesize any hormones.
– Serves as a storage area for ADH (vasopressin) and Oxytocin –produced by hypothalamus.
Neurohypophysis (posterior lobe)
“Stimulus” of ADH?
- Increased extracellular fluid osmolality
- Declining blood pressure or volume
- Non-specific stimuli: trauma, anxiety, nicotine, barbiturate anesthetics
Vasopressin is primarily synthesized in the _______
SON
-ADH is transported to the P-Pit & stored in axon terminals
“Effect” of ADH?
- ADH increases the water permeability of CD (V2 receptor & cAMP)
- Contracts vascular smooth muscle (V1 receptor, IP3)
-increased aquaporin expression in the nephron
Oxytocin is secreted by the _____.***
PVN
-Short half life (3-5 min)
Where is oxytocin stored/released?
by the posterior pituitary.
Where are the major sites of action of oxytocin?
Smooth muscle
1) Uterus 2) Mammary gland
-Critical role in lactation & during labor
1) stimulates the epithelial cells surrounding the mammary glands
(Milk ejection)
2) Uterine smooth muscle contraction
3) Psychological function: as a neurotransmitter
OXYTOCIN
Stimulus for oxytocin release…
- Suckling: sensory receptor send afferent signal to the CNS generating AP in neurons with nerve endings in the p-Pit which
release oxytocin - Distention of uterus & cervix: during pregnancy & movements of the infant result in transmission of neural signals to the CNS.
Subsequent AP release oxytocin from the p-Pit - Stimulation of the cervix during sexual intercourse also sends signals to release oxytocin from the P-pit
Frequency & force of oxytocin-induced contractions sharply
enhanced in the presence of ___________.
estrogen
Role of Estrogen?*
1) Induces oxytocin receptors
2) Induces uterine prostaglandin synthetase
Produced by the lactotroph cells in the anterior pituitary
PROLACTIN [LACTOGENIC HORMONE]
Stimulus of Prolactin release…
- the development of breast tissue for lactation
- initiation and maintaining lactation
- synthesis of milk proteins
What can cause hyperprolactinemia?
Drugs & pituitary tumors (Prolactinoma)
-Hyperprolactinemia —> Galactorrhea & Gynecomastia
Growth hormone is secreted by ___________ cells in A. Pituitary.
somatotroph
Growth hormone is controlled by _______.
GHRH (hypothalamus)
-Less so by somatostatin
✴ Stimulus for GH release…
- AA (particularly Arg)
- Ingestion of a protein meal
- Starvation
- Hypoglycemia
- Exercise, stress, excitement, trauma
- Sleep
How does growth hormone increase protein synthesis?
a) increases AA transport into cells
b) increases RNA synthesis
c) increases Ribosomal protein synthesis
d) decreases Protein catabolism
How does Growth hormone “spare blood glucose”?
Stimulate lipolysis & lipid utilization
-Net result: blood glucose rises
How does GH inhibit carbohydrate (CHO) utilization?
-increases glycogen deposition
-decreases cellular glucose uptake once glycogen stores are saturated
GH stimulates the release of ____________ from liver and kidney.
somatomedin
(peptide growth?, insulin-like growth factor?)
-excess GH in adults
-enlarged bones
Acromegaly
excess GH pre-puberty
Gigantism
– pre-puberty deficiency of GH
➡ small stature but proportionally built
dwarfism
E3, placenta?
Estriol
E1, (P menopause, cancer)
Estrone
E2?
estradiol
-estrogen C-18
What are the 3 distinct tissues of the adrenal cortex (from outside to inside)?
– Zona glomerulosa (G zone)
– Zona fasciculata (F zone)
– Zona reticularis (R zone)
- Has a high lipid content and produces steroid hormones
layer of the adrenal gland that is Composed of sheets of irregular cells with small nuclei called*
-Chromaffin cells (involved with epinephrine?)
Inner layer: adrenal medulla
What are the cells associated with Chromaffin cells?*
Pheochromocytes, neuroendocrine cells
The primary mineralcorticoid produced & secreted by Zona Glomerulosa
aldosterone
How is aldosterone transported?
Transported by Albumin & Corticosteroid Binding Globulin
What is the function of aldosterone?
-sodium reabsorption
-K+, H+ and Mg2+ excretion
-Regulates extracellular fluid volume
➢ increase blood volume & blood pressure via the Renin-Angiotensin system
is a protein produced by the JGA of the kidney in response to decreased renal perfusion pressure or decreased serum Na+ levels.
Renin
Renin acts on _____________ (liver) to produce angiotensin I, which is converted to angiotensin II by ACE present in the vascular endothelium of
the lung & kidney.
angiotensinogen
Angiotensin II is converted to angiotensin III by an aminopeptidase. AngII
is a potent vasoconstrictor. Both AG-II & AG-III can bind to the receptor on
the target cell (in adrenal cortex) which stimulates the secretion of _________.
aldosterone
What are the two ways the renin-angiotensin system increases blood pressure?
by vasoconstriction and increased plasma volume
angiotensin ___ —> vasoconstriction.
2
The primary glucocorticoid produced & secreted by Zona Fasciculata
Cortisol: Hydrocortisone
How is cortisol transported?
transported bound ( >95%) to plasma proteins
(albumin & CBG)
** a decrease in free [cortisol] in the serum stimulates hypothalamus to secrete ____________.
corticotropin (ACTH)
ACTH stimulates _____________ to secrete cortisol.
zona fasciculata
What converts Angiotensin II to Angiotensin III?
Aminopeptidase A
What are the functions of cortisol?
-gluconeogenesis in liver (increase glucose)
-affects metabolism of protein and fat
-stimulates erythropoiesis
-anti-inflammatory
How is cortisol catabolized?
liver & kidneys.
▪ < 2% free cortisol (active) is filtered
& excreted by kidney
What is cortisol measured as?***
17 hydroxy corticosteroids
Why is 17 hydroxy corticosteroids measured in the lab for cortisol?
-water soluble
-metabolized product of cortisol
-urine sample
Target Tissues of cortisol?
Target tissues: kidney (glomerulus & tubule), bone marrow stem cells, hepatocytes, & adipose tissue.
___________ are metabolites of testosterone and adrenal steroid hormones.
17-ketosteroids
Adrenal Androgens:
Steroid hormones, produced by ___________.
Secretes precursors to androgens (mostly Androstenedione)
Zona Reticularis
a monoamine that contains catechol and amine side chain
catecholamine
Hormones produced by adrenal medulla
❖Produces ________-by hydroxylation of the tyrosine.*
e.g. Epinephrine (E), norepinephrine(NE)
catecholamine
What is the function of catecholamine?*
▪Neurotransmitter (SNA)
▪ Increase blood pressure, heart rate, and blood sugar
What is the stimulus of catecholamine production?*
▪ Released in response to pain & emotional disturbance
How adrenal medulla hormones transported?*
free in blood and regulated by feedback
Metabolites of catecholamine?*
metanephrine & normetanephrine
“ Vanillylmandelic acid (VMA) (enzyme: monoamine oxidase)
Metabolism of medullary hormones:
What are the metabolites that are measured in lab?
-Catechol Methyltransferase (COMT)
-Monoamine oxidase (MAO)
Hyperaldosteronism:
increased serum and urine aldosterone
-metabolic _________
alkalosis
increased pH due to decreased hydrogen
Symptoms of hyperaldosteronism?
-fatigue and weakness
-hypertension
Types of Hyperaldosteronism:
- Aldosterone secreting adrenal adenoma or adrenal
hyperplasia - Something wrong with the adrenal gland itself.
1° hyperaldosteronism (Conn’s syndrome)
-tumor/cancer
Excessive production of renin resulting in increased
aldosterone production
2° hyperaldosteronism
Hypoaldosteronism (isolated)
➢ Lack of aldosterone production could be due to:
-Damaged adrenal gland
▪ Decreased renin production by kidneys or
▪ G layer (G zone) enzyme deficiency
________ is key factor to release cortisol***
ACTH
➢ Decreased production of adrenal hormones
Cortisol and/or Aldosterone
Adrenal insufficiency (Addison’s disease)
Types of adrenal insufficiency?
➢ 1° Adrenal insufficiency
▪ damaged adrenal Cortex (~ 90%)
➢ 2° Adrenal insufficiency
▪ ACTH deficiency (abnormality at the pituitary level)
symptoms of Addison’s disease?
dehydration, decreased
kidney function, shock (can occur due to decreased blood pressure)
How is ACTH effected with adrenal insufficiency?*
-increased with primary
-decreased with secondary
How is plasma Na+ and aldosterone effected with adrenal insufficiency?
-decreased with primary
-normal with secondary
How is H+ and K+ effected with adrenal insufficiency?
-increased with primary
-normal in secondary
What is Cushing’s syndrome?
Hypercortisolism due to increased cortisol production by:
* adrenal gland (primary)
* increased ACTH release from pituitary (secondary)
Cushing’s syndrome/ hypercortisolism:
ex: adenoma (only 10% cases)
* No regard for feedback from ACTH
* Labs: ↑ Fasting blood glucose (FBG), ↑ plasma cortisol, ↓ ACTH,
↑ urinary free cortisol
1° disease
Cushing’s syndrome/ hypercortisolism:
hyperpituitarism (pituitary cushing’s)
– or –hyper ACTH secretion due to tumor (Ectopic cushing’s)
* Labs: ↑ FBG, ↑ plasma cortisol,↑ ACTH, ↑ urinary free cortisol
– 2 ° disease
Symptoms of Cushing’s?
▪fat face (moon face),
▪enlarged fat between shoulder blades (buffalo hump)
▪Fat body and skinny arms and legs (centripetal fat
distribution)
▪Increased serum glucose (steroid diabetes)
PHEOCHROMACYTOMA:
Catecholamine producing tumors arising from the __________
of adrenal _________.
chromaffin cells, medulla***
-Tumors lead to the production and release of large quantities of
catecholamine.*
PHEOCHROMACYTOMA:
labs?
urinary metanephrines, VMA***
PHEOCHROMACYTOMA:
symptoms?
Headache, periodic sweating, hypertension***