Hypothalamic-Pituitary Relationships Flashcards
What is one of the first symptoms that occurs when you have a problem with your hypothalamus?
Why?
Visual problems
Pituitary gland is encased in bone; if a tumor or problem occurs, it goes up into the brain and compress the optic N lies
Hypothalamus is broken into smaller ____ with _____.
Nuclei with cell bodies
Communications between the anterior pituitary gland and the hypothalamus are ____, ____, and ____.
Neural signals synapse on ____.
Connected to hypothalamus by the ___.
Neuronal, hormonal, vasculature
Vasculature bed
Hypophysial portal system
Anterior pituitary secretes what hormones?
ACTH TST FSH LH GH Prolactin
_____ can be directly delivered to the anterior pituitary gland.
They do not appear in ____ concentration in systemic circulation.
Hormones
High
A collection of axons whose cell bodies are located in the hypothalamus and extend into the ____.
What are the cell bodies in the hypothalamus called?
What does it secrete?
Posterior pituitary gland
Supraoptic nucleus (SON)
Paraventricular nucleus (PVN)
ADH (SON)
Oxytocin (PVN)
Communication between the hypothalamus and posterior pituitary is a _____ signal.
Communication between the hypothalamus and anterior pituitary is _____ communication.
Neuronal
Hypothalamic-hypophysial portal system (vascular)
Abnormal amounts of a hormone can be due to a dysfunction at different levels of the endocrine axis.
What are the levels and where do they come from?
Tertiary endocrine disorder: hypothalamus
Secondary: pituitary gland
Primary: peripheral gland
Hormones of the anterior pituitary are organized into families by structure and function. What hormones are in each family and where are they secreted from?
ACTH family?
TSH, FSH, LH family?
GH, prolactin family?
Hypothalamus -> target in anterior pituitary -> hormone
CRF -> Corticotrophs secrete ACTH
TRH -> Thyrotrophs secrete TSH
GnRH -> Gonadotrophs secrete FSH and LH
GHRH stimulates ;somatostatin (GHIH) inhibits-> Somatotrophs secrete GH
PIF (dopamine) inhibits; elevated TRH stimulates -> Lactotrophs secrete prolactin
What drives endocrine relationships?
This activity is maintained at a ___ point.
Hypothalamic neurons are secreted in a _____ manner to a _____ rhythm (secreted up and down)
Axes
Set
Pulsatile
Circadian
What are the anterior pituitary gland axes? (6)
Hypothalamic-pituitary-gonad (HPG)
Hypothalamic-pituitary-liver
Hypothalamic-pituitary-prolactin
Hypothalamic-pituitary-reproductive (testis/ovaries)
Hypothalamic-pituitary-thyroid
Hypothalamic-pituitary-adrenal
Disease characterized by excessive growth of soft tissue, cartilage, and bone in the face, hands, and feet and develops gradually
What causes this?
Symptoms?
Acromegaly
Prolonged and excessive secretion of GH in adult life
Prominent supraorbiral ridges Organomegaly Hyperglycemia Lower teeth separation Prominent lower jaw Enlarged head Mental disturbances Accelerated osteoarthritis Hypertension
GH or somatotropin is produced by ____ in _____.
Targets ____ and ___.
GH receptor linked to ____ signaling.
Inhibited by ____.
Somatotropes; anterior pituitary
Liver and bone
JAK-STAT
Somatostatin (GHIH) and IGF-1 (insulin related growth factor 1; part of the negative feedback)
How does GH target the liver?
How does this negative feedback to GH secretion?
Causes the liver to release IGF-1, which can target the bone, muscle, skin
IGF-1 inhibits GH secretion (negative feedback)
What stimulates GH?
Fasting/hunger/starvation Hypoglycemia Exercise Sleep Stress Hormones of puberty
What are the direct actions of GH?
Growth: hypertrophy (increase size/volume of cells)
Cell reproduction: hyperplasia (increase number of cells)
Metabolism: increases glycogen and fat breakdown for energy; increases protein synthesis
What are the indirect actions of GH?
Tropic function
Signals liver to produce IGF (insulin-like growth factor)
IGF Stimulates hypertrophy and hyperplasia
Explain the three levels of the hypothalamic-pituitary-growth hormone axis
Hypothalamus: GHRH, GHIH (somatostatin)
Anterior pituitary: GH (somatotropin)
Liver: IGF, IGF-1 (somatomedin C)
**Gastric fundal cells: secrete ghrelin to stimulate GH release
Explain the hypothalamic-pituitary-growth hormone axis (HPGh) and its use of negative feedback
IGF-1 can inhibit the release of GH from the anterior pituitary or stimulate the release of GHIH from the hypothalamus
GH can inhibit the release of GHRH from the hypothalamus
Gigantism caused from excess ___.
Gigantism occurs ____ closure of bone epiphyses due to excess stimulation of long bone growth by ____.
Acromegaly occurs ____ closure of bone epiphyses due to promotion of growth of _____.
Growth hormone
Before
IGF-1
After
Deep organs and cartilaginous tissue
What are growth promoting factors during a fed state?
This causes the liver to do what?
Increase carb intake and increase blood sugar cause adequate insulin availability
AND
Increase protein intake causes adequate AA availability
Both cause liver to produce IGF-1 causing mitogenesis, lypolysis, differentiation
What are unfavorable growth conditions during a fed state?
This causes inhibition of what?
Casing the liver to do what?
Adequate carb and blood sugar levels but decreased protein intake and inadequate AA availability
Therefore GH is inhibited
Liver doesn’t produce IGF-1 -> lipogenesis and carb storage (weight gain)
What causes growth factors to shift in the fasting state?
What does peripheral metabolism shift to?
This causes the increase of what?
Causing the liver to do what?
Low carb intake, hypoglycemia, inadequate insulin availability but high protein intake and adequate amino acid availability
Shifts from carbs to lipids as an energy source
Increase GH levels
Liver produce IGF-1 -> lipolysis, ketogenic metabolism, diabetogenic (can result in insulin insensitivity)
Metabolic fx of GH
Diabetogenic effect (increase blood sugar): causes insulin resistance, decrease glucose uptake, increase lipolysis, increase blood insulin
Increase protein synthesis and organ growth: increase uptake of AA, stimulates synthesis of DNA, RNA, protein; mediated by somatomedins (IGF-1)
Increase linear growth: stimulates synthesis of DNA, RNA, protein; mediated by somatomedins, increase metabolism in cartilage-forming cells and chondrocytes proliferation
When is the biggest secretion of GH?
During sleep
During puberty
Peaks with exercise
What causes GH deficiency?
GH excess?
Decrease secretion of GHRH, decrease GH secretion, failure to generate somatomedins, GH or somatomedin resistance (deficiency of receptors)
GH-secreting adenoma, gigantism before puberty, acromegaly after puberty
How do you diagnose acromegaly?
GH and oral glucose tolerance test
When given oral glucose, pt’s secretion of GH should be inhibited; but in pt with acromegaly GH is not suppressed
Failure to suppress serum GH leads to IGF-1 levels remaining constant throughout the day
Pituitary enlargement on MRI
Tumor causing excessive hormone production from pituitary gland
Examples?
Pituitary adenoma
Prolactinoma (most common)
Acromegaly/gigantism
Cushing’s disease
What secretes prolactin? From what?
When does secretion begin?
What kind of secretion?
What inhibits it?
Action?
Lactotropes; anterior pituitary
5th week of pregnancy
Pulsatile
Under tonic inhibition by hypothalamic dopamine
Stimulate and maintain lactation; suppresses GnRH (inhibit LH and FSH) to decrease reproductive fx and suppress sexual drive
Stimulators of prolactin secretion
Inhibitors of prolactin secretion
Pregnancy (estrogen), Brest-feeding, sleep, stress, TRH
Dopamine, dopamine agonists, somatostatin, prolactin by negative feedback
Describe the three levels of the prolactin cascade
Hypothalamus: TRH, dopamine (inhibits)
Anterior pituitary: prolactin
Mammary glands: Lactation
FDH and LH secreted by what? From?
Action?
What regulates secretion?
Gonadotropes; anterior pituitary
Estrogen and progesterone secretion in females for normal menstruation; testosterone production in males
Hypothalamic GnRH (GnRH can be inhibited by energy deficits, anorexia, extreme exercise, depression)
Hyperprolactinemia suppresses what hormones that act on what organ?
How?
Symptoms of excess prolactin?
FSH and LH; ovaries
Prolactin inhibits GnRH from hypothalamus -> inhibits secretion of FSH and LH from anterior pituitary
Galactorrhea, infertility
What causes hypopituitarism?
Brain damage
Pituitary tumor (adenoma)
Non-pituitary tumor (craniopharyngioma most common)
Infections (meningitis, encephalitis, hypophysitis)
Infarction (Sheehan syndrome: the pituitary is in larger during pregnancy)
Autoimmune disorders
Pituitary hypoplasia
Genetic disorders
Disease when the pituitary is enlarged and more vulnerable to infarction during pregnancy
Causes hypopituitarism
Sheehan syndrome
Disease causes by lack of effect of ADH on renal collection duct
Results in polyuria
What is the normal function of ADH?
Diabetes insipidus (DI)
Normally ADH induces permeability of the renal collecting duct so it absorbs water
In DI, water is not absorbed, therefore polyuria, dilute urine
Symptoms of diabetes insipidus
What are the two types of DI?
Polyuria, polydipsia, polyphagia
Central: deficient secretion of ADH from hypothalamus or pituitary
Nephrogenic: renal insensitivity to ADH
How do you diagnose diabetes insipidus?
What differentiates between central and nephrogenic DI?
- WATER DEPRIVATION TEST: to assess the ability of the pt to concentrate urine when fluids are withheld
Drink normal fluids, obtained baseline urine osmolality, withhold water and measure osmolality, administer desmopressin and measure osmolality
Normal function: urine will concentrate
Diabetes insipidus: urine will stay diluted even when dehydrated
Central DI: urine will concentrate when desmopressin is given (kidneys work)
Nephrogenic: urine will stay diluted with desmopressin
- ADH TEST to differ between central and nephrogenic DI: Test urine output, challenge with ADH, retest urine output
Central: kidneys respond by concentrating urine, problem with brain
Nephrogenic: kidneys can’t concentrate urine, problem with kidneys
Types of DI:
Lack ADH, decrease plasma ADH, damage to posterior pituitary or hypothalamus; desmopressin test successful
Kidney unresponsive to ADH, increase plasma ADH, chronic kidney disease, lithium toxicity; desmopressin test unsuccessful
Central DI
Nephrogenic DI
Disease causing excess secretion of ADH, excessive water retention, hyponatremia
Hypoosmolarity fails to inhibit ADH release
Explain hyponatremia
SIADH
Hyponatremia is caused by ADH induced water retention; the high volume activates secondary natriuretic mechanisms (aldosterone) that cause Na and water loss; net effect with chronic SIADH is Na loss is more prominent than water retention
What hormones do the posterior pituitary gland secrete?
Oxytocin and ADH
What are the two actions of oxytocin?
How are these actions stimulated?
Milk ejection: stimulates contraction of myoepithelial cells lining milk ducts
Stimulated by suckling, sight, sound, smell of infant
Uterine contractions: stimulated by dilation of cervix or orgasm; pitocin (induction of labor)
Summary of the control of the hypothalamic-anterior pituitary hormones
CRH -> increase ACTH, MSH
Dopamine -> decrease prolactin
GHRH -> increase GH
GnRH -> increase FSH, LH
Prolactin -> decrease GnRH (leading to decrease FSH/LH)
Somatostatin -> decrease GH, TSH
TRH -> increase TSH, prolactin
Explain GH insensitivity
What kind of deficiency is it?
Primary deficiency because problem with gland
GHRH is released from the hypothalamus, causes GH secretion from the anterior pituitary
However, during GH insensitivity, the LIVER will not respond to GH, therefore IGF will not be secreted
More GH is secreted because more is needed to induce a response from the liver
Explain a secondary GH deficiency
Tertiary deficiency of GH
GHRH is secreted from the hypothalamus but the anterior pituitary does not respond and GH levels don’t rise; IGF not secreted
GHRG is not secreted from the hypothalamus so no signal is relayed
How do you diagnose acromegaly?
Elevated serum GH and IGF-1 levels
AND
Failure to suppress GH production in response to oral load of glucose test
(high amounts of sugar should feedback and inhibit GH secretion; but if that fails, and has elevated GH and IFG-1, pt could have acromegaly)
What do estrogen and testosterone inhibit in their feedback mechanism?
What also alters FSH release?
They inhibit the release of FSH and LH from the anterior pituitary
Estrogen feedback depends on menstrual cycle
Ovaries also secrete inhibit and activin that alter FSH release
Compare the mechanisms and causes of euvolemic and hypervolemia hyponatremia
Euvolemic: extracellular Na normal, TBW increased
Causes: SIADH, COPD, malignancy
Hypervolemia: extracellular Na increased, TBW greatly increased
Causes: CHF, renal impairment, cirrhosis
Compare SIADH to DI
Urine output: low, high ADH: high, low or normal Plasma Na: low, high Hydration status: high, low Thirst: high, high Body water content: normal or high, low
