Endocrinology Flashcards
Prehormone syntheiss occurs in the __________ and is directed by a specific mRNA
endoplasmic reticulum
__________ are cleaved from prehormone. producing prohormone, which is transported to the Golgi apparatus
Signal peptides
Addtional peptide sequences are cleaved in the golgo apparatus to form the _________, which is packaged in secretory granules for later release
Hormone
Steroid hormones are derivatives of _____________
Cholesterol
Amine hormones (Thyroid hormones, epinephrine, norepinephrine) are derivatives of ___________
tyrosine
Most commonly applied principle for regulating hormone secretion
self limiting
Negative feedback
Explosive and self reinforcing regulating principle of hormone secretion
Positive feedback
Stimulates secretion of TSH and prolactin
Thytotropin releasing hormone (TRH)
hypothalamus
Stimulates secretion of ACTH
CRH
hypothalamus
Stimulates secretion of LH and FSH
GnRH
Stimulates secretion of growth hormone
GHRH
Hypothalamus
Inhibits secretion of growth hormone
Somatotropin release-inhibiting hormone (Somatostain)
Hypothalamus
Inhibits secretion of prolactin
Prolactin-inhibiting hormone (dopamine)
hypothalamus
Stimulates synthesis and secretion of thyroid hormones
TSH
anterior pituitary
Stimualtes growth of ovarian follicles and estrogen secretion.
Promotoes sperm maturation (testes)
FSH
anterior pituitary
Stimulates ovulation, formation of corpus luteum, and synthesis of estrogen and progesterone (Ovary)
Stimualtes synthesis and secretion of testosterone (testes)
LH
Anterior pituitary
Stimualtes protein synthesis and overall growth
GH
anterior pituitary
Stimulates milk production and breast development
Prolactin
anterior pituitary
Stimulates synthesis and secretion of adrenal cortical hormones
ACTH
anterior pituitary
stimulates the synthesis and secretion of adrenal cortical hormones
ACTH
Anterior pituitary
Stimulates melanin synthesis
MSH
Anterior pituitary
Milk ejection, uterine contraction
OXytocin
posterior pituitary
Stimulates water reabsorption by renal collecting ducts and contraction of arterioles
ADH
Posterior pituitary
Skeletal growth; increase oxygen comsumption, heat production, increase protein, fat and CHO use; maturation of nervous system (perinatal)
L-Thyroxine
Triiodothyronine
Thyroid gland
Stimualtes gluconeogenesis; antiinflammatory; immunosuppression
Glucocorticoids
adrenal cortex
Growth and development of female reproductive organs; follicular phase of menstrual cycle
Estradiol
Ovary
Luteal phase of menstrual cycle
Progesterone
Ovary
Spermatogenesis; male secondary sex characteristics
testosterone
Testes
Increase serum calcium, decrease serum phosphate
PTH
parathyroid gland
Decrease serum calcium
Calcitonin
Thyroid gland (parafollicular cells)
Increase renal sodium reabsorption, increase renal K secretion, Increase renal H secretion
Aldosterone
adrenal cortex
Increase intestinal sodium reabsotpion, increase bone mineralization
1,25 dihydroxycholecalciferol
Kidney (activation)
Decrease blood glucose, decrease blood amino acid, decrease blood fatty acid
Insulin
Pancrea (Beta cells)
Increase blood glucose, increase blood fatty acids
Glucagon
Pancrea (alpha cells)
increase estrogen and progesterone synthesis in copus luteum of pregnancy
HCG
Placenta
Same actions as growth hormone and prolactin during pregnancy
Human placental lactogen
Placenta
Hormones determine the sensitivity of target tissue by regulating the __________________
number or sensitivity of receptors
- Down-regulation
- Up-regulation
- in the ovary ,estrogen upregulates its own receptor for LH
______are GTP proteins that couple hormone receptors to adjacent effector molecules
G proteins
G proteins are used in the ___________ and __________ second messenger systems
Adenylate cyclase
IP3
G proteins have 3 subunits ____________
alpha
beta
gamma
the _______ subunit can bind either GDP or GTP.
alpha
- when GDP is bound = INACTIVE
- when GTP is bound = ACTIVE
hormones that uses cAMP mechanism
- ACTH
- LH and FSH
- TSH
- ADH (v2 receptor)
- HCG
- MSH
- CRH
- B1 and B2 receptors
- Calcitonin
- PTH
- Glucagon
Hormones that uses IP3 mechanism
GnRH
TRH
GHRH
ATII
ADH (V1 receptor)
Oxytocin
Alpha 1 receptors
Hormones that uses Steroid hormone mechanism
Glucocorticoids
Estrogen
Testosterone
Progesterone
Aldosterone
Vit. D
Thyroid hormone
Hormones that uses tyrosine kinase
Insulin
IGF-1
Growth hormone
Prolactin
Hormones that use cGMP mechanism
ANP
Nitric oxide
Adenylate cyclase mechanism
- Hormone binds to a receptor
- GDP is released from the G protein and relpaced by GTP
- Activated adenylate cyclase catalyzes ATP to cAMP
- cAMP activates protein kinase A
- cAMP is degraded to 5’ AMP by phosphodiesterase
- inhibited by caffeine
IP3 mechanism
- Hormone bind to receptor activates phopholipase C
- via cell membrane
- via a G protein
- Phospholipase C liberates diacylclycerol and IP3
- IP3 mobilizes calcium from ER. Activates protein kinase C
Guanylyl cyclase
- ANP
- Acts through a receptor gyanylyl cyclase. where the extracellular side of the receptors binds ANP and the intracellular side has guanylyl cyclase activity
- NO
- acts through cytosolic guanylyl cyclase
- converts GTP to cyclic GMP, which is the second messenger
Receptor tyrosine kinase
- bind to extracellular side of the receptor
- Intracellular side has intrinsic tyrosine kinase actovoty
- monomer
- dimer
- insulin
- insulin growth factor
mechanism of action of growth hormone
tyrosine kinase-associated receptor
- GH binds to the extracellular side of the receptor
- The intracellular side of the receptor does not have tyrosine activity but is non covalently associated with tyrosine kinase (JAK)
Steroid hormone and thyroid hormone mechanism
- Steroid hormone diffuses across the cell membrane and binds to its receptor
- Hormone-receptor complex enters the nucleus and dimerize
- The hormone-receptor dimers are transcription factors that bind to steroid responsive elements (SREs) and initiate DNA transcription
- New mRNA is produced
- the new protein hace specific physiologic functions
The __________lobe of the pituitary gland is linked to the hypothalamus by the hypothalamic-hypophysial portal system
Anterior
The ________ lobe of the pituitary gland is derived from neural tissues. The cell bodies are located in the hypothalamic nuclei
Posterior
TSH, LH, and FSH belong to the same glycoprotein family. The _________ subunit are identical
Alpha
ACTH, MSH, B-lipotropin and B-endorphin are derived from a single precursor, __________________
Proopiomelanocortin
______ and ______ are produced in the intermediary lobe, which is rudimentary in adult human
Alpha and BEta MSH
Most important hormone for normal growth to adult size.
Growth hormone
Growth hormone is a single chain polypeptode that is homologous with _______ and _______
Prolactin
human placental lactogen
Growth hormone is relased in a __________ manner
pulsatile
Growth hormone secretion is increased by _______________
Sleep, stress, hormones related to puberty, starvation, exercise and hypoglycemia
Growth hormone secretion is decreased by ____________
Somatostatin, somatomedins, obesity, hyperglycemia and pregnancy
__________ ar eproduced when growth hormone acts on target tissues. They inhibit secretion of GH by acting directly on the anterior pituitary and by stimulating secretion of somatostain from the hypothalamus
Somatomedins
Negative feedback control by GHRH and GH
- GHRH inhibits its own secretion from the hypothalamus
- GH also inhibits its own secretion by stimulating the secretion fo somatostatin from the hypothalamus
in the liver, GH generates the production of ________________, which serves as the intermediaries of several physiologic actions
Somatomedins (insulin-like growth factor)
- the IGF receptor has tyrosine kinase activity
Growth hormone deficiency
- Lack of anterior pituitary GH
- hypothalamic dysfunction
- Failure to generate IGF in the liver
- Growth hormone receptor deficiency
Growth hormone excess can be treated with ____________
Somatostatin analogs (octreotide) which inhibit growth hormone secretion
Hypersecretion of growth hormone causes __________
Acromegaly
- Before puberty = increased linear growth (gigantism)
- After puberty = causes increased periosteal bone growth, increased organ size, and glucose intolerance
Major hormone responsible for lactogenesis
Prolactin
- Participates with estrogen, in breast development
- structurally homologous to growth hormone
Prolactin secretion is tonically inhibited by _____________
Dopamine
- TRH increases proalctin secretion
Regulation of prolactin secretion
Actions of prolactin
- Stimulates milk production
- Stimulates breast development
- Inhibits ovulation (decreasing synthesis and relase of GnRH)
- inhibits spermatogenesis
Prolactin excess
- hypothalamic destruction (loss of inhibitory control)
- prolactinomas
- galactorrhea
- Failure to ovulate and amenorrhea
Prolactin excess can be treated with _________
bromocriptine
Hormones of the posterior lobe of the pituitary
ADH and Oxytocin
- synthesized in the hypothalamic nuclei
- package in secretory granuleswith their respective neurophysins
- travel down the nerve axons by secretion by the posterior pituitary
ADH originates primarily in the ___________ ofthe hypothalamus
supraoptic nuclei
- Regulates serum osmolarity by increasing water permeability of the late distal tubules and collecting duct
Factors that increase ADH secretion
- Serum osmolarity
- volume contraction
- Pain
- Nasuea (powerful stimulant)
- Hypoglycemia
- Nicotine , opiates, antineoplastic drugs
Factors that decrease ADH secretion
- Decrease serum osmolarity
- ethanol
- alpha agonists
- ANP
Actions of ADH
- Increase water permeability (aquaporin 2) of the principal cells of the late distal and collecting ducts (via V2 receptor and adenylate cyclase- cAMP mechanism)
- Constriction of vascular smooth muscle (via V1 receptor and an IP3/calcium mechanism)
Oxytocin origanates primaruly in the ____________ of the hypothalamus
paraventricualr nuclei
- causes ejection of milk from the breast when stimualted by suckling.
Major stimulus for oxytocin secretion
Suckling
- Afferent fibers carry impulses from the nipple to the spinal cord. Relays in the hypothalamus trigger the release of oxytocin from the posterior pituitary
Actions of oxytocin
- contraction of myoepithelial cells in the breast
- Contraction of the uterus
- reduce post partum bleeding
_______is synthesized from tyrosine in the thyroid follicular cells, packaged in secretory vesicles, and extruded into the follicular lumen
Thyroglobulin
___________ present in the thyroid follicular epithelial cells
Actively transports I into the thyroid follicular cells for subsequent incoporation into thyroid hormones
The iodide (I) pump or Na-I cotransport
- Inhibited by thiocyanate and perchlorate anions
Oxidation of I to I2 is catalyzed by ___________ in the follicular cell membrane
Peroxidase
- I2 is the reactive form, which will be “organified” by combination with tyrosine on thyroglubulin
The peroxidase enzyme is inhibited by _________, which is used therapeutically to reduce thyroid hormone syntheis for the treament of hyperthyroidism
Propylthiouracil
Organification of I2 involves tyrosine residues of thyroglobulin react with I2 to form _________ and ____________
Monoidotyrosine and Diiodotyrosine
High levels of Iodide inhibit organification and therefore inhibit synthesis of thyroid hormone
Wolff-Chaikoff effect
Coupling reactions of MIT and DIT
- When 2 molecules of DIT combine, T4 is formed
- when 1 DIT combines with 1 MIT, T3 is formed
Leftover MIT and DIT are deiodinated by ___________. The I2 that is released is reutilized to synthesize more thyroid hormones
Thyroid deiodinase
In the circulation, most of the T3 and T4 is bound to __________
thyroxine-binding globulin
- In hepatic failure, TBG levels decreases, leading to decrease in total thyroid hormone levels, but normal levels of free hormone
- In pregnancy, TBG levels increase leading to an increase in total thyroid hormone levels, but notmal levels of free hormone