Chapter 75 Flashcards
What is the HPA?
hypothalamus pituitary axis.
What is the most dominant portion of the entire endocrine system?
HPA
What does the output of the HPA regulate?
- Thyroid gland
- Adrenal gland
- Reproduction
- Somatic growth
- lactation/milk secretion
- water metabolism
What does pituitary function depend on?
hypothalamic releasing hormones.
What does the hypothalamus link together?
nervous system to endocrine system via the pituitary gland
What is the hypothalamus the collecting center for?
homeostatic information: Body temp, hunger, thirst, circadian cycle
What is the hypothalamus responsive to?
- light
- olfactory stimuli
- steroids
- neurally transmitted info
- autonomic inputs
- blood-borne stimuli
- stress
- temp
What does the hypothalamus secrete and synthesize?
neurohormones and HRIH (hypothalamus releasing/inhibiting hormones)
Where are neurohormones transported to?
posterior pituitary along axons from neural bodies
Where are neurohrmones stored?
in terminal axons.
Where are HRIH released?
into median eminence and tuber cinereum of hypothalamus into the hypohysial portal
What does the HRIH control?
secretions of hormones by the anterior pituitary (adenohypophysis)
What is the vascular connection to the pituitary?
HRIH via blood control anterior pituitary
hypothalamic-hypophysial portal vessels.
What are the neural connections to pituitary?
nerve signals control posterior pituitary secretion of neurohormones made in hypothalamus
What are the two categories of hypothalamic output?
- neural projections
- endocrine hormones.
What are the neural projections of hypothalamic output?
multiple fiber system
- connects Hypothalamus to different areas of CNS
- neurohormones created in the hypothalamus secreted to the neurohypophysis then into circulation
Where are most hormones generated by the hypothalamus distributed to?
pituitary via the hypophyseal portal system
Where are posterior pituitary hormones synthesized?
magnocellular neurons of the supraoptic nuclei (ADH) & paraventricular nuclei (oxytocin) of the hypothalamus
What are the posterior pituitary hormones synthesized from?
from prohormones:
peptide + binding peptide (neurophysin)
Neurophysin travels in secretory granules along axon to posterior pituitary for secretion
Vasopressin/Antidiuretic Hormone (ADH)
Oxytocin
Does the posterior pituitary produce hormones?
No it only secretes hormones produced in hypothalamus.
What does the neurohypophysis consist of?
primarily of hypothalamic axons supported by glial-like cells called pituicytes.
What is anatomically and embryologically continuous with the hypothalamus
neurohypophysis
Are there neural bodies in the posterior lobe?
no!
What is the outgrowth of the hypothalamus?
neural tissue
Where are hormones that are secreted from the neurohypophysis synthesized?
in supraoptic and paraventricular nuclei of hypothalamus
If the stock is cut above the pituitary will the posterior pituitary hormones continue to be secreted?
yes, because the hormones are synthesized in neural bodies in the hypothalamus.
What are the posterior pituitary hormones and where are they produced?
Antidiuretic hormone (ADH)/Vasopressin primarily produced in supraoptic nuclei
How is ADH regulated?
- Osmotic concentration of fluid
- Decreased blood volume
How is osmotic concentration of fluids detected?
by osmoreceptors in hypothalamus and major arteries
Does ADH increase or decrease with concentration?
increase with concentration (low blood volume)
decreases with dilution
What does ADH influence in the kidney?
collecting ducts
What does underfilling of atria, aorta, carotid, and pulmonary vessels lead to?
unexcited stretch/baroreceptors and very high concentrations of ADH are produced to cause constriction of arterioles and increase arterial pressure
What does ADH bind to?
G protein coupled receptor on tubular cell
What activated adenyl cyclase to make cAMP?
alpha subunit
After alpha subunity activate adenyl cyclase and makes cAMP what is activated?
protein kinase cascade
What is inserted in the cell membrane after the protein kinase cascade starts?
vesicles containing aquaporins
What is the final step in the cellular mechanism of ADH?
absorption of water from collecting tubules.
What does an insufficient secretion of ADH lead to?
diabetes insipidus
what is diabetes insipidus?
body loses capacity to concentrate urine
affected individuals excrete as much as 20 L of dilute urine/day
What does and oversecretion of ADH lead to?
SIADH - syndrome of inappropriate ADH secretion
What is associated with SIADH?
a variety of ADH secreting tumors
various CNS disorders
pulmonary disorders
drugs
What is the cause of diabetes insipidus?
- deficiency of ADH
- insensitivity of kidneys to ADH
What are the symptoms of diabetes Insipidus?
- increased frequency of urination
- nocturia
- enuresis
- increased thirst
- increased fluid consumption
- dehydration - too much water being excreted
What are the causes of SIADH?
- excess ADH secreted from autonomous site
- head injury
- drugs (SSRIs, MDMA)
what is hyponatremia? and what is it associated with?
not a deficiency of sodium, rather a water excess.
SIADH
what does dilution hyponatremia cause?
headaches nausea vomiting confusion convulsions coma (same side effects from attending neurophys lectures)
Where is oxytocin produced?
paraventricular nuclei
What does oxytocin help with?
partuition and expressing milk from breast glands during lactation
What is the only hormone to produce positive feedback? and during what event does this occur?
Oxytocin
-labor! gross
What are the 5 steps in breast feeding that are associated with oxytocin?
1) suckling
2) signals via sensory nerves to oxytocin neurons via hypothalamus
3) increased oxytocin carried by blood to breast
4) contraction of myoepithelial cells
5) milk ejection
When is oxytocin secreted in men?
during ejaculation
How does oxytocin function as a neurotransmitter?
decreases fear response by amygdala and influences pair bonding
How is the anterior pituitary connected to the hypothalamus?
by the hypothalamic-hypophysial portal system
How does the hypothalamus control secretions of anterior pituitary hormones?
via HRIH which are secreted and synthesized by neurons in median eminence of hypothalamus
What are the 6 HRIH’s?
- Thyrotropin-releasing hormone (TRH u TSH)
- corticotropin -releasing hormone (CRH u ACTH)
- growth hormone-releasing hormone (GHRU u ^hGH; GHIH (somatostatin) u, hGH
- gonadotropin-releasing hormone (GnRH u LH/FSH)
- prolactin inhibitory hormone (dopamine) (PIH)
- Prolactin releasing hormone (PRH u PRL)
What is the effect of CRH?
stimulate ACTH
What is the effect of TRH?
stimulate TSH and prolactin secretion
What is the effect of GHRH?
stimulate GH secretion
what is the effect of somatostatin?
INHIBITS: GH (& TSH, insulin, gastrin, glucagon, secretin, VIP)
what is the effect of GnRH?
stimulates secretion of LH and FSH
What is the effect of PRF/H, TRH, VIP?
stimulates PRL secretion
What is the effect of prolactin inhibiting hormone (dopamine)?
inhibits PRL secretion
When are HRIHs secreted?
in pulses
What do HRIHs act on?
specific membrane receptors
How do HRIHs transduce signals?
via second messengers
What do HRIHs stimulate?
- release of stored pituitary hormones
- hyperplasia, and hypertrophy of target cells.
What do HRIHs stimulate and inhibit?
synthesis and release of pituitary hormones
Are HRIHs monospecific?
not always!
What is the path of HRIHs from Hyopthalamus to anterior pituitary gland? and what do they regulate?
HRIH –> capillaries of pituitary portal system at median eminence –> anterior pituitary gland.
regulate secretion of pituitary hormones.
What does the pituitary help regulate?
- Growth
- pregnancy and childbirth
- breast milk production
- sex organ function
- thyroid function
- metabolism
- water and osmolarity
- blood pressure
Which artery (specifically) connects hypothalamus to adenohypophysis?
superior hypophyseal artery
What does the adenohypophysis produce and secrete?
peptide hormones that regulate: stress, growth, reproduction
What does the adenohypophysis contain (in regards to cells)
endocrine cells originating from ectodermal cells (rathkes pouch)
What kind of tissue is the adenohypophysis?
cellular and vascular
What is the adenohypophysis composed of?
5 types of glandular cells (-tropes)
What do the 5 types of glandular cells of the adenohypophysis produce?
6 peptide (trophic or tropic) hormones
What 5 glandular cells are produced in the adenohypophysis?
1) somatropes (30-40%)
2) corticotropes(20%)
3) thyrotropes ((3-5%)
4) gonadotropes (3-5%)
5) lactotropes (3-5%)
What hormone does somatotropes produce and what do they target?
Human growth hormone (GH)
targets liver, all tissues
What hormone does corticotropes produce and what is their target?
adrenocorticotropic hormone (ACTH) targets adrenal glands, melanocytes, adipocytes
What hormone does thyrotropes produce and what is their target?
thyroid-stimulating hormone
targets thyroid gland
What hormone do gonadotropes produce and what is their target?
luteinizing hormone (LH), follicle stimulating hormone (FSH) targets ovaries, testes
What hormone do lactotropes produce and what is their target?
prolactin (PRL)
Target breast, ovary, testes.
What does prolactin stimulate?
development of mammary glands and secretion of milk
What does cortisol do?
raises glucose levels in the blood and its comes from the adrenal cortex and ACTH
How does prolactin stimulate lactation in postpartum?
estrogen and dopamine production by the placenta inhibit milk production in pregnancy - when placenta is expelled and estrogen decreases, milk production ensues in 1-7 days.
Describe prolactin vs oxytocins function is regards to milk.
prolactin is involved in milk production while oxytocin is for milk ejection
When do serum levels of prolactin begin to rise?
5 weeks gestation to 10-20x at birth.
What inhibits prolactin?
- PIH, aka dopamine
- GABA, dopaminergic meds
What stimulates prolactin?
- TRH
- Sleep
- Stress
- nipple stimulation (oh la la)
- VIP via hypothalamus
- serotonergic pathways
- estrogen therapy
- Drugs (dopamin antags, MAO-I)
What is a prolactinoma?
pituitary adenoma
What causes a hyperprolactinemia?
pituitary tumor - women, menstrual dysfunction: short luteal phase, anovulation, oligomenirrhea, infertility.
men: decreased testosterone, decreased spermatogenesis, infertility, impotence, decreased libido, gynecomastia
What are the most common causes of moderately raised prolactin levels?
prescription drugs.
What do 40% of prolactinomas produce, and is it significant?
prolactin. and NO
What is a cause of prolactinomas?
hyperprolactinemia
Why would hypothyroidism cause hyperprolactinemia?
because TRH stimulates prolactin
What tissues does Growth hormone effect? and how?
all of them! by increasing cell size, increased mitosis, and specific differentiation of bone/muscle cells.
What does synthesis of GH stimulate?
GHRH from hypothalamus
What does inhibitory somatostatin block?
action of GHRH on somatrophs
When is the largest “burst” of GH?
within 1 hour after falling asleep. sleep stages 3 and 4.
When does secretion rate of GH increase?
from birth to childhood - enormous burst at puberty. then levels off.
Where does GHRH attach?
to receptor on surface of GH cell (somatotropes) in adenohypophysis
What does the GHRH receptor activate?
JAK/STAT (enzyme linked signaling)
What is the short-term effect of JAK/STAT?
increase Ca2+ transport into cell and cause fusion of GH vesicles on cell membrane for secretion into blood
What is the long term effect of JAK/STAT?
increase transcription in somatotrope nucleus to stimulate synthesis of new GH
What is the “theory” of GHRH?
GH controlled mainly by negative feedback mechanisms and diurnal pulses.
What is the process of GH negative feedback?
1) GHRH stimulates GH –> short feedback inhibition to hypothalamus to inhibit GHRH
2) GH stimulates somatostatin (GHIH) in hypothalamus, which inhibits GHRH in an ultra-short feedback inhibition
3) GH stimulates production of somatomedins
What two ways do somatomedins participate in GH negative feedback?
1) indirect: stimulating somatostatins production by hypothalamus
2) direct: inhibiting GH production in somatotropes of adenohypophysis
What factors inhibit GH?
- obesity
- hyperglycemia
- elevate [FA] in blood
- aging
- GHIH
- somatomedins
What factors stimulate GH?
- starvation, fasting, malnutrition, protein deficiency
- hypoglycemia
- low [FA] in blood
- exercise
- excitement, trauma, stress
- testosterone, and estrogen
- deep sleep
- serotonin, dopamine, catecholamines
- GHRH
What are the metabolic effects of GH?
1) increased protein synthesis
2) increased mobilization of FA in blood
3) decreased rate of glucose utilization
4) stimulates cartilage and bone growth
How does GH increase protein synthesis?
- increase AA transport
- increase DNA transcription, increased RNA
- Decreased catabolism of AA and proteins
- increases synthesis, decreases catabolism*
Why are Kwashiorkor patients GH levels high?
they have severe protein deficiency
What can help maintain GH levels?
supplementing with carbohydrates
What does low protein production stimulate?
GH. - supplemeting patients with complete protein lowers serum GH
How does GH increase FA utilization?
- increase release of FA from adipose
- increases conversion of FA to acetyl CoA (fat used for energy instead of CHO & protein)
- increase in overall lean body mass
- ketogenic effects
How does GH decrease CHO use?
GH conserves CHO (increase gluconeogenesis, increased blood glucose, increased insulin secretion, decreased glucose uptake and use by mm and adipose)
What is diabetogenic?
GH = “diabetogenic” or “hyperglycemic” - GH-induced insulin resistance and diabetes.
What is the theory of Gh decreasing CHO use?
GH causes an increase in FFA that makes the liver and mm resistant to insulin’s actions (increase insulin secretion, with decrease effectiveness)
How does GH stimulate cartilage and bone growth?
- increased deposition of protein by chondrocytes and osteocytes
- increased rate of reproduction of both cell types
- converts chondrocytes into osteocytes
What do somatomedians mediate?
bone growth
What are IGFs?
insulin-like growth factors - small proteins produced by liver and other tissues in response to GH
If GH is applied directly to chondrocytes does it promote growth?
NO
What happens when somatomedin C and IGF-1 amounts are decreased?
dwarfism
What is panhypopituitarism?
decreased secretion of all anterior pituitary hormones
- congenital
- can be a tumor, or thrombosis etiology
What are symptoms of panhypopituitarism?
LOW GH
hypothyroidism, decreased glucocortocoids, decreased gonadotropins
What are characteristics of dwarfism?
-mostly panhypopituitarism in childhood
-development proportional, but rate is decreased
-lack of puberty, sexual/repro functions
LOW GH
What percent of dwarfism is GH only deficiency?
1/3. sex/repro function intact
What are the characteristic of gigantism?
HIGH GH
GH cell tumor or excessively active GH cells
-rapid growth of all tissues
-overproduction of GH causes glandular burnout, preadolescent GH excess can cause height up to 8 feet.
What will panhypopituitarism due to burnout lead to if untreated?
DEATH
What is acromegaly?
extremities enlargement
what is acromegaly caused by?
GH cell tumor after adolescence. (benign)
- bones become thicker, soft tissues grow
- middle aged adults most common affected
What is GH as a treatment for?
dwarfism (GH only deficient)
other metabolic disorders
How is hGH synthesized?
from e coli via recombinant DNA
What is the pineal gland AKA?
epiphysis
What does the pineal gland do?
synthesizes and secretes melatonin (ability to coordinate biological rhythms)
Why do some call the pineal gland the “third eye”?
because of its light-transducing ability
What is the pineal gland regulated by?
Sympathetic nervous system - transduces signals from sympathetic into a hormonal signal
What does the pineal gland regulate?
gonadal function and development in season breeders and chronobiologic rhythms
What is secretion f melatonin from the pineal gland stimulated by?
hypoglycemia and darkness.
What is length of melatonin secretion proportional to?
length of darkness/night
What is the path of transmitting light from retina to pineal gland?
1) light exposure to retina
2) superchiasmatic nucleus of hypothalamus
3) hypothalamic fibers
4) spinal cord
5) superior cervical ganglia
6) post-ganglionic neurons ascend back to pineal
7) pineal transduces signals from SNS to hormonal signal
What are the effects of melatonin on reproduction?
Melatonin is anti-gonadotropic.
- melatonin inhibits secretion of gonadotropic hormones LH/FSH via inhibiting GnRH
- elevated in non-breeding season = inhibition of reproduction
What is the normal function of melatonin on sleep?
helps decrease skeletal muscle activity and body temp to induce sleep.
What effect does melatonin have on RA patients?
melatonin increases pro-inflammatory cytokines like TNF-a.
What kind of levels of melatonin do breast cancer patients have?
low serum melatonin. Melatonin inhibits growth of breast tissue.
