pituitary hormones and hypothalamic control Flashcards
____ secretes small protein “releasing factors”, except for prolactin
hypothalamus
releasing factors
target anterior pituitary via portal system
anterior pituitary releases which 6 hormones in response to RFs
- somatotrophin (GH)
- Thyrotopin (TSH)
- Follicle stimulating H (FSH)
- Corticotropin (ACTH)
- Prolactin
- Luteinizing hormone (LH)/gonadotropic hormones
posterior pituitary releases —
oxytocin and vasopressin (antidiuretic hormone, ADH)
pituitary gland is known as —
hypophysis
pituitary gland is connect to the hypothalamus by the ____
pituitary/hypophyseal stalk
anterior pituitary contains how many types of secretory cells?
5
somatotropes
- –> growth hormone
- single chain of 191 amino acids
- stimulates body growth; stimulates secretion of IGF-1; stimulates lipolysis
- inhibits actions of insulin on carb and lipid metabolism
thyrotropes
- -> thyroid stimulating hormone (TSH; thyrotropin)
- stimulates production of thyroid hormones by thyroid follicular cells
- maintains size of follicular cells
what are conduced to the anterior pituitary via hypophysial portal vessels?
hypothalamic-releasing and inhibitory hormones
all hormones increase secretions, except the secretion of ____, which is inhibited by ______
all hormones increase secretions, except the secretion of prolactin, which is inhibited by dopamine
______ receives nervous signals from almost all possible sources in NS—collecting center of information for control of secretion by pit gland
hypothalamus
thyrotropin-releasing hormone
causes release of thyroid-stimulating hormone (TSH, thyrotropin) from anterior pit
corticotropin-releasing hormone (CRH)
causes release of adrenocorticotropin from anterior pit
growth hormone-releasing hormone (GHRH)
causes release of growth hormone from anterior pit
growth hormone inhibitory hormone (GHIH)
somatostatin
-inhibits release of GH (somatotropin)
gonadotropin-releasing H (GnRH)
causes release of LH and FSH
prolactin-inhibitory hormone (PIH/dopamine)
causes inhibition of prolactin secretion–elevated dopamine release from HT inhibits prolactin from the anterior pituitary
growth hormone
- somatotropin
- released from anterior pit by GHRH
- small, single chain protein that binds to cell membrane receptors that have “catalytic” property
- affects all/almost all tissues of body
- promotes growth of tissues capable of growing: increased cell size and mitosis – stimulate cartilage and bone growth
- metabolic effects
growth hormone’s effect is manifested through
weight gain
growth hormone’s protein deposition effect in tissues:
- enhancing amino acid transport through membrane
- enhancing mRNA translation for protein synthesis by ribosomes
- increased nuclear transcription of DNA to form mRNA
- decreased catabolism of protein and amino acids
GH increases almost all facets of ______ and ______, while decreasing ______ of proteins
increases amino acid uptake and protein synthesis while decreasing breakdown of proteins
effect of GH on fat utilization
- increases fat utilization for energy
- causes increased release of fatty acids from adipose tissues and their utilization with ketogenic effect
GH decreased cab utilization by
- decreasing glucose uptake/utilizatioon in tissues such as skeletal muscle (increases blood glucose)
- increases glucose production by liver (stimulation of gluconeogenesis, thus increases blood glucose)
- increases insulin secretion (resistance occurs)
how does GH stimulate cartilage and bone growth?
- stimulates epiphyseal cart or growth of plates of long bones
- stimulation of chondrocytes in growth plate leads to cell proliferation and increase in secretion of collagen and deposition of cartilage, followed by conversion of cartilage to bone
- increased osteoblast number and activity
somatomedins
- intermediate substances GH uses to exert most of its effect indirectly
- insulin-like growth factors (IGFs) and somatomedin C
- from the liver
GH induces a more rapid effect directly, but a delayed/prolonged effect indirectly with _____
somatomedins
what factors stimulate growth hormone secretion?
- decreased blood glucose (hypoglycemia)
- decreased blood free fatty acids
- starvation or fasting, protein deficiency
- trauma, stress, excitement
- exercise
- testosterone, estrogen
- deep sleep
- growth hormone-releasing hormone
what factors inhibit growth hormone secretion?
- increased blood glucose
- increased blood free fatty acids
- aging
- obesity
- growth hormone inhibitory hormone (somatostatin)
- growth hormone (exogenous)
- somatomedins (insulin-like growth factors)
incomplete or partial proteins diet
a diet lacking one or more of the essential amino acids required for protein synthesis
kwashiorkor
- failure to grow
- lethargy
- depression
- low plasma protein
- hypoprotein edema
- on only a corn meal diet, lacking tryptophan
patients with kwashiorkor have increased plasma ____ and protein supplementation brings down the plasma hormone level towards normal, while relieving symptoms
GH
panhypopituitarism
decreased secretion of all the anterior pituitary hormones
dwarfism
- ateliotic dwarfs–deficiency of GH during childhood
- laron or levi-loraine dwarfs and African pygmy–rate of growth hormone secretion is normal or high, but there is a hereditary inability to form somatomedin C (GH insensitivity)
giantism/gigantism
GH hypersecretion (usually due to tumors)
- before adolescence (before epiphysis fuse)
- overall growth increases
acromegaly
- GH hypersecretion after adolescence (after epiphyseal closure)
- certain body parts particularly become large (hands, feet, lower jaw, facial bones)
- hyperglycemia
aging associated with:
- low level of GH
- decreased protein deposition in body esp in muscles
- increased fat deposits
- feeling of decreased energy
- wrinkling of skin
- administering GH improves some of the conditions in some pts
posterior pit contains 2 types of cells (pituicytes) with what in between?
nerve fibers and blood capillaries
nerve fibers for posterior pituitary originate where?
in 2 hypothalamic nuclei
-terminals store and secrete hormones on capillary surfaces in PP, which then join the circulation
antidiuretic hormone (ADH, vasopressin)
-primarily formed in supraoptic nucleus of the HT
oxytocin
formed primarily in the paraventricular nucleus of HT
In the posterior pit, each nucleus synthesizes about ____ as much of the second hormone as its primary hormone
one sixth
ADH and oxytocin are each a _____ polypeptide
9 amino acid polypeptide (nano-peptide)
similarities between oxytocin and antidiuretic hormone
- both initially formed in HT as prohormones and then transported to PP via nerve tracts to be stored
- both are nanopeptides, differing only in 2 amino acid residues
- produce effects by binding to CM/surface receptors
- each is secreted into general circulation and transported to target tissues
ADH deficiency results in —-
diabetes insipidus, a condition associated with excessive urination and thirst
functions of ADH (vasopressin)
antidiuresis
vasoconstriction/pressor effect
antiduiresis
- ADH decreases excretion of water by the kidneys
- increases permeability of collecting ducts and tubules to water (by increasing aquaporin insertion via V2 receptor activation and increasing cAMP)
- conserves water–> concentrated urine
- ADH controls rate of water secretion into urine, helping regulate concentration of water/electrolyte in body fluids
vasoconstriction
vasopressin (ADH) causes vasoconstriction and blood pressure increase
-mech related to constriction of arterioles via V1 receptor activation, which increases IP3 and Ca (usually occurs with high ADH release)
osmotic regulation
- antidiuretic effect of ADH
- concentrated electrolyte solution in plasma increases ADH secretion to retain water and maintain normal osmolality
- dilute solution/plasma decreases ADH secretion
blood volume regulation (vasopressin)
- decreased blood volume increases ADH secretion
- increased blood volume decreases ADH secretion
two major functions of oxytocin
- causes contraction of uterus towards end of gestation, helping delivery of baby
- aids milk ejection by breast by inducing myoepithelial cells around breast ducts to contract
release of oxytocin
- suckling stimuli on nipple of breast causes release of oxytocin by PP, which contracts myoep cells to eject milk (milk letdown reflex)
- distention of cervix during partition generates neurohormonal reflex to cause increased secretion of oxytocin (positive feedback mech)
where are T3 and T4 synthesized?
follicular cells in thyroid
two major hormones made in thyroid gland
- thyroxine (T4)–93% initially
2. triiodothyronine (T3)–7%
how are hormones secreted into circulation from the thyroid?
thyroid stimulating hormone (TSH, thyrotropin) which is released from the anterior pituitary
T4 is eventually converted into —-
T3 in target tissues
what is needed for the synthesis and release of T3 and T4?
iodine, thyroglobulin and enzymes
path of synthesis and release of T3 and T4
- follicular cell synthesizes enzymes and thyroglobulin for colloid
- Iodine is cotransported into cell with Na and transported into colloid
- enzymes add iodine to thyroglobulin to make T3 and T4
- thyroglobulin is taken back into cell
- intracellular enzymes separate T3 and T4 from protein
- free T3 and T4 enter circulation
thyroglobulin
precursor protein for iodine-containing thyroid hormones, T4 and T3
iodide originally consumed with food is taken up from circulation and changed to ?
molecular iodine I2
organification of iodine
binding of iodine with thyroglobulin
substances made from organification and coupling
monoiodotyrosine, diiodotyrosine, 3,5,3-triiodothyronine, thyroxine
what breaks the bond between T3 and T4?
proteases
MIT, DIT, t3 and t4 all undergo what?
pinocytosis
T3 and T4 are released into circulation by ?
protease enzymes
T3 and T4 are transported in combination with?
plasma proteins–thyroxine-binding globulin (major), thyroxine-binding pre-albumin, albumin
TH are released relatively _____ compared to other hormones
slowly
1/2 of T4 in blood released into tissues every — days and 1/2 of T3 every —- days
6 days and every day
effects of TH are produced by _____ binding and- _____ of nuclear receptors
effects of TH are produced by direct binding and activation of nuclear receptors which then interacts with specific DNA structures to ultimately generate new proteins (but steroids produce effects by first binding to cytosolic receptors)
effects of T3 and T4 on metabolism
increase
- mitochondira
- NA K ATPase
- O2 consumption
- glucose absorption
- gluconeogenesis
- glycogenolysis
- lipolysis
- protein synthesis
- Body Basal Metabolic rate**
how do you measure basal metabolic rate
oxygen consumption
pharmacokinetics on basal metabolic rate based on a single injection of T4
- slow onset (2-3 days)
- long duration (6-8 weeks)
- if you increase the dose of T4 –> increases BMR
the effect of TH on growth is manifested in ___
children
hypothyroidism in children
retarded growth in general, including growth and development of brain during fetal life and first few years of postnatal life
hyperthyroidism in children
excessive skeletal muscle growth (but mature more rapidly, and duration of growth and eventual height shortened)
effect of TH on specific bodily metabolism
- stim of carb metabolism
- stim of fat metabolism
- increased requirement for vitamins
- increased BMR
- **decreased body weight
effect of TH on cardiovascular system
- increased blood flow and cardiac output
- increased heart rate
- increased heart strength
- normal arterial pressure (BP)
other systemic effects of TH
- increased respiration
- increased GI motility (diarrhea)
- excitatory effect on CNS causing muscle tremors
- effect on sleep-insomnia
lack of TH in women causes–(hypo)
menorrhagia (excessive menstrual bleeding)
polymenorrhea (freq menstrual bleeding)
greatly decreased libido
hyperthyroid women–
oligomenorrhea (greatly reduced bleeding)
amenorrhea (absence)
lack of TH in men–
loss of libido
excess TH causes impotence (can’t perform)
effect of TSH on thyroid gland
- increased proteolysis of thyroglobulin (increased release of hormones)
- increased activity of iodine pump
- increased iodination of tyrosine
- increased size and secretory activity of thyroid cells
- increased number of thyroid cells
what mediates the stimulatory effect of TSH on thyroid gland?
cAMP
how is amount of T3 and T4 regulated
negative feedback loop on TRH (thyroid releasing hormone)
hyperthyroidism
toxic goiter, thyrotoxicosis or Graves disease
- caused by autoimmune/inflamm problem, adenoma, drugs/chemicals
- manifested by symps of hyperthyroidism, exophthalmos and goiter
- -sometimes inflamm (Hashimotos) and drug impair can cause HYPOthyroidism
**general symptoms of hyperthyroidism
- increased BMR, HR but decrease in PVR
- increased pulse pressure but not mean arterial pressure
- high state of excitability
- intolerance to heat
- increased sweating
- mild to extreme weight loss
- diarrhea
- nervousness, confusion, irritability
- insomnia, extreme fatigue
- tremor
- osteoporosis
symptoms of exophtalmos
- protrusion of eyeball due to retro-ocular deposition of mucopolysaccharides
- thyroid stimulating antibodies which cause hyperactivity of gland are also believed to cause this
symptoms of goiter
- enlargement of thyroid
- hyperthyroidism caused by action of thyroid stimulating antibodies on gland
hypothyroidism
- cretinism (children) and myxdema (adults)
- opposite symptoms of hyperthyroidism
myxedema symptoms
- deficiency of TH in adults
- swollen face with eye bags
- constipation
- increase BMI and arteriosclerosis
- increase body weight
- anemia, decreased blood volume
- slow HR/bradycardia
- mental dullness, sluggish response, somnolence
- depressed hair growth and scaliness
- froglike voice
- sexual atrophy and amenorrhea
- increased sensitivity to cold
cretinism symptoms
- hypothyroidism in children
- congenital–lack of thyroid gland or no TH
- endemic–iodine lack in diet
- failure to grow normally
- mental retardation
- obese and short
- growth inhibited
endemic goiter
caused by dietary iodine deficiency
underdeveloped countries
idiopathic non-toxic colloid goiter
- problem with iodine use
- caused by thyroiditis, which induces mild hypothyroidism, leading to increased TSH and thyroid enlargement
dental implications of hyperthyroidism
- nervousness, increasaed sensitivity to pain
- tremor and muscle weakness
- increased bone loss, cardiac activity, palpitation, arrhythmia, highly sensitive to epinephrine
- osteoporosis of bone, dental caries, Perio disease
- rapid teeth and jaw development, early loss of teeth
dental implications of hypothyroidism
- hyperlipidemia, cardiac dysfunction, osteoporosis
- delayed eruption of teeth, malocclusion, skeletal growth retardation
- tongue enlargement
- increased capillary fragility, exaggerated resp to CNS depressants
