Hypothalamic-Pituitary relationships Flashcards
How is the anterior pituitary connected to the hypothalamus?
by hypothalamic-hypophysial portal vessels
Do hypothalamic hormones appear in the systemic circulation in high concentration?
No
They appear in high concentration in the hypothalamic-hypophysial portal vessels
What are the connections between the hypothalamus and anterior lobe ?
Via median eminence and portal system: Neural and endocrine
What are the connections between the hypothalamus and posterior lobe?
neural axons via neuro-hypophyseall stalk
ACTH has melanocyte-stimulating hormone activity. Explain the clinical relevance
Increase blood levels of MSH can cause skin pigmentation
Addison disease ACTH levels increase, Skin pigmentation is a symptom
POMC-> ACTH + Y-lipotropin + B-Endorphin
Describe the HPA axis
Major hormones: CRH->ACTH
Target organs: medulla and cortex adrenal gland
peripheral hormone: aldosterone, cortisol, sex horm
Regulations: stress - neurogenic (fear) or systemic (surgery)
Hypothalamus has the ability to reset the set point in response to stress
Describe the HPT axis
TRH->(PKC mechanism) TSH->(PKA mechanism) thyroid gland->T3/T4
Regulation: stress - physical, starvation, infection inhibits TRH secretion
Describe the HPG axis
GnRH->(Ca, PKC, other) FSH and LH->gonands and thyroid(PKA mech.) ->estrogen and testosterone
Regulation: stress inhibits via inhibin
Puberty promotes
What stimulates GH secretion?
Decreased blood glucose levels: ghrelin->GH release
Secreted in pulsatile pattern every 2 hours
GHRH->GH
What is the lifetime pattern of growth hormone secretion?
Peaks at puberty then declines
What are the direct and indirect effects of growth hormone?
Direct: effect on tissues like skeletal muscle, liver, adipose tissue
Indirect: mediated by the production of somatomedins in the liver (IGF-1)
What are the actions of growth hormone?
Diabetogenic effect
Increased Protein synthesis and organ growth
Increased linear growth
The diabetogenic effect directly results in what actions of GH?
Body not using glucose but using fats
Results in increase in blood insulin levels from liver, skeletal m, adipose tissue
Leads to insulin resistance
Decrease in glucose uptake and utilization
Increase in lipolysis in adipose tissue (ketogenic)
what is the hypophysial stalk?
physical connection between hypothalamus and (posterior) pituitary gland
What inhibits the release of growth hormones from the anterior pituitary?
Target tissues release somatomedins which directly inhibits
Somatomedins also stimulate the hypothalamus to secrete somatostatin which inhibits the anterior pituitary
Describe the action of Growth hormone from the indirect effect of somatomedins
Stimulate synthesis of DNA, RNA, and proteins
Protein synthesis and organ growth: increase uptake of aa
Increase linear growth: Increase metabolism in cartilage-forming cells and chondrocytes proliferation
What are causes of growth hormone deficiency ?
Decrease secretion of GHRH - hypothalamic
Decrease in GH secretion - 1* deficiency
- failure to generate somatomedins
GH or somatomedin resistance - receptor deficiency
What does growth hormone excess cause?
acromegaly
Before puberty: gigantism
After puberty: increase organ size, extremities size, insulin resistance, glucose intolerance
What is excessive growth hormone in the body usually caused by?
GH- secreting pituitary adenoma
What are conditions with excess secretion of GH treated with ?
somatostatin analogues like octreotide
With combined actions of progesterone and estrogen, what role does prolactin play in breast development?
At puberty: stimulate proliferation and branching of mammary ducts
During pregnancy: stimulates growth and development of the mammary alveoli
What role does prolactin play in lactogenesis?
Induces synthesis of lactose, casein, and lipids
Why does lactation not occur during pregnancy even though prolactin levels are high?
High levels of estrogen and progesterone down-regulate prolactin receptors
How is inhibition of lactation released at birth?
Estrogen and progesterone levels drop precipitously, when this occurs lactogenesis is stimulated
What is prolactin’s role in ovulation?
suppresses ovulation
inhibits synthesis and secretion of GnRH
What results in prolactin deficiency? What are the causes?
Inability to lactate
Causes: destruction of the entire anterior lobe of the pituitary or selective destruction of the cells that secrete prolactin (lactotrophs)
What results in prolactin excess?
Galactorrhea (excessive milk production) and infertility (caused by inhibition of GnRH secretion by prolactin
What are the causes of prolactin excess levels?
destruction of hypothalamus or the interruption of hypothalamic-hypophysial tract; loss of tonic inhibition by DA (dopamine)
Prolactinomas
What can be used to treat prolactin excess?
Bromocriptine (DA receptor agonist) can be used for the treatment of prolactin excess
What are the 3 sources of dopamine?
Hypothalamus, posterior lob of pituitary and lactotroph
How does the destruction of the hypothalamus cause in INCREASE in prolactin secretion
Dopamine cant be released from the hypothalamus/posterior lobe of the pituitary and thus cant inhibit prolactin secretion.
What is panhypopituitarism?
condition of inadequate or absent production of the anterior pituitary hormones
What are the causes of panhypopituitarism?
Problems that affect the pituitary gland and either reduce or destroy its function or interfere with hypothalamic secretion of the varying pituitary-releasing hormones
What is the most common tumor affecting the HP axis in children and causing hypopituitarism?
Craniopharyngioma
What is sheehan syndrome?
Pituitary in pregnancy is enlarge and more vulnerable to infarction
Most pituitary tumors are pituitary ________.
Adenomas
- most occur spontaneously
A pituitary adenoma is classified according to size. Describe the size of macro vs microadenoma
Micro or equal to 1 cm
What is the agressiveness of pituitary adenomas ?
nearly all are benign and slow-growing
Describe the hormone secretion of pituitary adenomas
Functional: adenomas that release an active hormone, usually an excessive amount
Clinically non-functioning adenomas: do not release active hormone
What is the most common functional pituitary adenoma?
prolactinoma: overproduces prolactin 60%
Acromegaly 20%
Cushing’s - overproduction of cortisol 10%
Pituitary adenomas develop in ____ of patients with MEN 1
25%
What is the precursor peptide of ADH?
preprossophysin
What is the precursor peptide for oxytocin?
prepro-oxyphysin
What is the major hormone concerned with regulating body fluid?
ADH
Describe the activation of ADH
In cell bodies of hypothalamus: cleaved from prepropressophysin to propressophysin
Cleavage of neurophysins and axoplasmic flow: in axons and becomes ADH
What are the triggers of ADH secretion
decreased blood pressure: baroreceptors Decrease arterial stretch due to low blood volume: atrial stretch receptors Increased osmolarity: osmoreceptors Increased angiotensin II Sympathetic stimulation Dehydration
All to sensory neurons and interneurons -> hypothalamus
What is the secretion of ADH most sensitive to?
plasma osmolarity changes
An increase in only 1% in osmolarity will increase ADH secretion
Urea can pass with water, but _______ cannot
electrolytes
What does ADH do in the renal collecting duct?
Through G protein V2 receptors, it increases cAMP via Adenylate cyclase activity
That Activates PKA
which increases the amount of aquaporin-2 causing more water to be reabsorbed
When there is less volume (contraction), how much ADH will be needed with increase in osmolarity?
More ADH secretion (steeper slope)
*expansion causes less ADH secretion
Describe ADH’s role in Diabetes insipidus
Lack of an effect of ADH on renal collecting duct
Causes frequent urination
Urine diluted
Describe Central diabetes insipidus
Lack of ADH
Low plasma levels of ADH
Results from: damage to pituitary, destruction of the hypothalamus
Tx: desmopressin (prevents water excretion
Describe nephrogenic DI
Kidneys unable to respond to ADH (increase in plasma ADH)
Caused by drugs like lithium and chronic disorders like polycistic kidney disease
Desmopressin tx does not work
What is the water deprivation test for DI?
Allow fluids overnight before test and give breakfast w/ no fluids
Weigh patients
Allow no fluid for 8 hr.
Every 1-2 hr: weigh
Stop of weight drops by >5% initial bw
Patient empties bladder: measure volume and osmolarity (stop if >300)
If results suggest DI, let pt drink and administer desmopressin
measure volume and osmolarity
What are the results of DI test if normal?
About 300 Osm plasma
Urine is 814 Osm
Plasma ADH is increased
Urine Osm post desmopressing is 815
What are the results of DI test if the pt has central DI
Plasma Osm = 342
Urine Osm = 102
Decreased plasma ADH
Urine Osm post = 622
What are the results of DI test with a nephrogenic DI pt?
Plasma Osm = 327
Urine Osm = 106
Increased Plasma ADH
Urine Osm post des = 118
Describe SIADH
Excessive secretion of ADH
Excessive water retention
Hypoosmolarity fails to inhibit ADH release
Causes: ectopic ADH with lung cancer, drugs, trauma, CNS disorders,
What is the Tx for SIADH?
fluid restriction
IV hypertonic saline
V2 receptor antagonist
Demeclocycline
What are the major consequences of pituitary failure
GH: short children
FSH/LH: infertility, hypogonadism, menstrual irregularity and reduce sperm
TSH: hypothyroidism
ACTH: Loss of pigmentation hypoadrenalism
ADH: diabetes insipidus
