Intro to Endocrinology Flashcards
What hormones does the hypothalamus produce?
GnRH CRH TRH PH GHRH Somatostatin Dopamine (PIH)
What hormones does the anterior pituitary produce
FSH LH ACTH TSH Prolactin GH MSH
What hormones does the posterior pituitary release?
Oxytocin
ADH
What hormones does they thyroid release?
T3,T4
Calcitonin
What hormones does the parathyroid release?
PTH
What hormones does the pancreas release?
Insulin
Glucagon
What hormones does the adrenal medulla release?
NE and epinephrine
What hormones does the kidney release?
renin
1,25-dihydroxycholecalciferol
What hormones does the adrenal cortex release?
cortisol
aldosterone
adrenal androgens
What hormones does the testes release?
testosterone
What hormones does the ovaries release?
Estradiol and progesterone
What hormones does the corpus luteum release?
estradiol and progesterone
What hormones does the placenta release?
HCG
Estriol
Progesterone
HPL
What are the three classes of hormones?
Proteins/peptides
Amines
Steroids
How many a.a. differentiate a peptide hormone from a protein hormone
100 a.a
Describe protein/peptide hormones
water-soluble; most are peptides
DNA->mRNA->preprohormone
in ER signal peptide removed to produce prohormone
Packaged into vesicles in Golgi, cleaved by proteolytic enzymes to generate active form
What could be a stimulus for exocytosis of protein/peptide hormones?
increased intracellular Ca caused by membrane depolarization
Activation of GPCR followed by increased cAMP, and activation of PKA
Describe amine hormones
derived from tyrosine
Two groups:
- thyroid hormones: synthesized by thyroid gland and stored as thyroglobulin in follicles; cross cell membrane, act on nuclear receptors
- Catecholamine (epinephrine, NE, dopamine): synthesized in cytosol and secretory granules; act through cell-membrane associated receptors
Steroid hormones are all derivates of _______, modified how
cholesterol
*modified by removal or addition of side chains, hydroxylation, or aromatization of the steroid nucleus
What are the steroid hormones found in the body?
Cortisol, aldosterone, estradiol, estriol, progesterone, testosterone
1,25-dihydroxycholecalciferol (technically not a steroid but it is derived from cholesterol)
What are the two sources of cholesterol?
80% taken up as LDL particles through receptor-mediated endocytosis (diet)
De novo synthesis from acetyl coenzyme A (acetyl CoA)
What Apo protein can be found on LDL particle?
Apo B - 100
What stimulates the release of catecholamines into circulation?
Preganglionic sympathetic nerves synapse on adrenal gland to regulate release
What is the genomic action of steroid hormones?
Common theory - modulate gene transcription by interactions with intracellular, nuclear receptors
What is the nongenomic actions of steroid hormones
Rapid steroid actions
Specific-receptor-mediated actions or direct steroid-membrane interactions
Compare and contrast the half lives and metabolic clearance of thyroid, steroid, and protein hormones
Thyroid: 1-6 days plasma half life; 1-20 ml/m metabolic clearance
Steroids: 25-100 min plasma hl; 200-1000 ml/m
Proteins: 10-50 min hl; 50-600 ml/m
Metabolic clearance = ?
(mg/minute removed)/(mg/ml of plasma) = ml cleared/min
Describe neural mechanism of endocrine regulation
Neuronal input to an endocrine cell increases or decreases hormonal secretion
Describe feedback mechanism of endocrine regulation
More common than neural mechanism
Negative feedback predominate
Describe positive feedback mechanisms
self-augmenting
leads to an explosive event
rarely used to maintain homeostatic function
- menstrual cycle: estrogen, increase FSH and LH release to increase estrogen for ovulation
- delivery of a fetus: oxytocin
What is the long-loop feedback?
negative feedback: hormone released from 3rd tier (peripheral endocrine gland) feeds back all the way to 1st tier (hypothalamus) and 2nd tier (pituitary)
What is short-loop feedback?
negative feedback: hormone secreted from 2nd tier (pituitary) to 1st (hypothalamus)
What is ultra short-loop feedback?
negative feedback: gland inhibits its own secretions
What are the endocrine axes?
Hypothalamus - pituitary - adrenal gland (HPA) axis
Hypothalamus - pituitary - thyroid gland (HPT) axis
Hypothalamus - pituitary - gonads (HPG) axis
What is physiological response-driven negative feedback?
also known as response-driven feedback
Secretion of a hormone is stimulated or inhibited by a change in the level of a specific extracellular signal
ex. insulin: regulates blood glucose levels, blood glucose concentration turns on or off insulin secretion
How is the first tier of the endocrine axes highly regulated?
by descending and ascending neural inputs
- suprachiasmatic nucleus
- pineal gland
physiological stress influences the release of hormones from the hypothalamus
What is the role of suprachiasmatic nucleus in regulation of 1st tier?
impose a circadian rhythm on the secretion of hypothalamic releasing hormones and endocrine axes
What is the role of the pineal gland in regulated 1st tier?
releases melatonin which feedback to the SCN information about day-night
What is responsive sensitivity?
Hormone concentration that produces 50% of maximal response (EC50)
How can responsiveness be changed?
changing # of receptors
Changing affinity of receptors for hormone
Describe upregulation
increase receptor # or sensitivity of target tissue when hormone levels are low
- increase synthesis of new receptors
- decrease degradation of receptors
- activate
Describe down-regulation
reduce receptor # or sensitivity of the target tissue when hormone levels are high for an extended period of time
Describe the adenylyl cyclase mechanism
1st messenger: hormones (FLAT, glucagon, PTH, calcitonin, HCG, MSH, CRH)
primary effector: adenylyl cyclase
2nd messenger: cAMP
secondary effector: PKA
Describe the phospholipase C mechanism
1st messenger: hormones (GnRH, TRH, GHRH, Oxytocin)
1* effector: Phospholipase C
2nd messenger: IP3/DAG/Ca
2* effector: PKC or calmodulin
Describe steroid hormone mechanism
Hormone: thyroid, glucocorticoids, aldosterone, estrogen, testosterone
No second messenger
act through cytosolic/nuclear receptors
hormone-receptor complex acts as transcription factor
What enzyme deactivates cAMP?
phosphodiesterase
Describe the steroid receptor
Monomeric phosphoproteins
Each receptor has 6 domains (A-F)
- E domain: steroid hormone binding domain
- C domain: highly conserved, has 2 zinc fingers, responsible for DNA binding
Describe the guanylyl cyclase mechanism
1st messenger: hormones
- ANP: acts through receptor w guanylyl cyclase activity
- NO diffuses to cytosol and activates cytosolic guanylyl cyclase
1* effector: guanylate cyclase
2nd messenger: cGMP
2* effector: PKG
Describe the RTK mechanism
Have intrinsic tyrosine kinase activity w/i the receptor molecule
When activated, the intrinsic tyrosine kinase phosphorylates itself and other proteins
ex. Nerve, epidermal, insulin and insulin-like growth factors receptors
Describe tyrosine kinase-associated receptors
JAK-STAT
associate non-covalently to proteins that have tyrosine kinase activity
Describe hypofunction of endocrine
Reduced production of specific hormones
Describe hyperfunction of endocrine
increased production of specific hormones
Describe mass lesions with endocrine disorders
Enlargement of the endocrine organ due to an underlying neoplasia or hyperplasia
What are the disorders of endocrine hyperfunction?
Neoplastic: benign (adenoma), malignant (adrenal cancer), or ectopic (SIADH)
Autoimmune: Graves’ disease
Latrogenic: cushings
Infectious/inflammatory: subacute throiditis
Activating receptor mutations: TSH
Disorders of endocrine hypofunction
Hemorrhage: Adrenal insufficiency
Nutritional: vit D
Enzyme defects: 21-hydroxylase deficiency
Autoimmune: addisons, hashimotos, type i DM
Latrogenic: hypothyroidism
Infectious/inflammatory: adrenal insufficiency
Hormone mutations: GH, AVP
What is the primary main cause of endocrine disorder?
Low or high levels of hormone due to defect in peripheral endocrine gland
thyroid
What is the secondary main cause of endocrine disorders?
Low or high levels of hormone due to defect in pituitary gland
What is the tertiary main cause of endocrine disorders?
low or high levels of hormone due to defect in hypothalamus
In addition to hormones secreted by classic endocrine glands, there are hormones synthesized by endocrine cells within organs whose primary function is not endocrine. Where are these cells?
Adipose tissue, heart, liver, kidney and GI tract
