L69: Endocrinology Basics Contd Flashcards
What are the categories of hormones?
Monoamines: catecholeamines, indoleamines
Peptides/Proteins
Steroids
What is the half life of monoamines?
Short (1-2 minutes)
What molecule are catecholeamines derived from?
Single tyrosine
What is the rate limiting enzyme for catecholeamine biosynthesis?
Tyrosine Hydroxylase: Converts Tyrosine to L-DOPA
What role do catecholeamines play?
Hormones and neurotransmitters
What is the sequence of events for catechoelamine biosynthesis?
Tyrosine-> L-Dopa->Dopamine-> NE -> Epinephrine
What endocrine role does dopamine play?
Tonic inhibition of prolactin in anterior pituitary
Where do dopaminergic neurons arise from ?
Arcuate nucleus in hypothalamus
What is required for norepinephrine function?
Sympathetic NS stimulation
Where is dopamine converted to NE?
Neurons by Dopamine-B-hydroxylase
What kind of neurons release NE?
Sympathetic post-ganglionic neurons
What receptors does NE act through?
alpha and eta adrenergic receptors
Where is NE converted to epinephrine?
Adrenal Medulla
What cells of the adrenal medulla release epinephrine?
Chromaffin Cells (Acts as postganglionic neuron)
What molecule are indoleamines derived from?
Single Tryptophan
What is the rate limiting enzyme for indoleamine biosyntehsis?
Tryptophan Hydroxylase
Is serotonin a catecholeamine or indoleamine?
Indoleamine
Where is serotonin made?
In the gut
What does serotonin do?
Vasconstrictor
Smooth muscle cell contraction stimulator in intestine
Where is melatonin made and from what precursor?
Made in the pineal gland from serotonin
How are monoamines inactivated?
Dopa Decarboxylase (DDC): decarbaoxylate L-Dopa to dopamine
COMT: Inactivate and degrade catecholeamines
MAO: deaminate monoamines
What is the end product of Epinephrine and NE metabolism?
Vanillylmandelic Acid (VMA)
What are SSRIs?
Selective SErotonin Reuptake Inhibitors: increases concentration of serotonin at synaptic cleft
Used to treat depression and other mental health disorders
What do MAO inhibitors do?
Increase dopamine levels
What are clnical considerations for SSRI uses?
Depression not well understood
Desensitization/Downregulation of postsynaptic receptors
Negative Feedback -> less serotonin produced in presynaptic cells
What is the rate limiting enzyme for melatonin synthesis?
N-Acetyltransferase: converts serotonin to melanin
Most active during the night
When is melatonin levels highest?
During Dark phases
What effect does melatonin have on reproduction?
Inhibits it; decreases spermatogenesis and testis size in males
How is light information conveyed?
Retinohypothalamic tract to the SCN -> Pineal Gland -> regulate circadian activity
What is the half life of peptides/protein hormones
2-170 minutes; longer if bound to transport proteins
How are peptide hormones synthesized and processed?
Transcribed as preprohormones with signal peptide sequence -> signal peptide cleaved-> prohormone (hormone + copeptides) -> processed and packaged into vesicles -> cleaves hormone from copeptides
Which hormones in the hypothalamus are peptide hormones?
Hypothalamic Releasing hormones
Which hormones in the pituitary are peptide hormones?
Trophic hormones
What are the peptide hormones?
Calcitonin, PTH, Insulin, Glucagon, Leptin, Renin/EPO, IGF-1, ANP/BNP
What is the half life of steroid hormones?
mnutes to hours
How are steroid hormones synthesized and processed?
STAR protein transports free cholesterol from outer to inner mitochondria -> P450/Desmolase converts cholesterol to Pregnenolone -> converted to glucocorticoids, mineralocorticoids, androgens, estrogens
What are some examples of positive feedback mechanisms?
Partuition: child birth: contractions stimulate oxytocin release from hypothalamus -> more contractions -> more oxytocin (Cycle stopped by birth)
Lactation: Suckling stimulates oxytocin release from hypothalamus) -> more suckling-> more oxytocin (lack of suckling stops loop)
Ovulaiton: LH stimulates estradiol in follicle -> estradiol stimulates more LH (Release of oocyte stops loop)
Blood Clotting: Tissue injury activates platelets-> platelets activate more platelets-> clotting stops cycle
What is the difference between primary, secondary, and tertiary endocrine diseases?
Primary: defect at peripheral gland
Secondary: defect at pituitary gland
Tertiary: defect at hypothalamus?
What is long loop feedback?
Peripheral gland hormone inhibits pituitary and/or hypothalamic hormones
What is short loop feedback?
Pituitary hormone inhibits hypothalamic hormones
What is the TRH stimulation test and how is it interpreted?
Diagnose cause of hypothyroid Symptoms
Primary Defect: High basal TSH levels but normal pituitary response to TRH given via IV (Thyroid)
Secondary Defect: Undetectable basal TSH levels and no pituitary response to TRH given via IV (Pituitary)
Tertiary Defect: Low basal levels of TSH and delayed return to baseline after TRH given via IV (Hypothalamus)
What factors affect the circulating levels of hormones?
Age, body weight, time of day, gender, diet
Which is used for diagnostic tool, ANP or BNP and why?
BNP due to its longer half life than ANP
What does a normal BNP level tell you?
Can rule out CHF
What does a high BNP level tell you?
ASsociated with risk of heart/renal failure
How is BNP affected by weight, age and gender?
Lower with obesity
Increases with age
Higher in women