L3 - Anterior Pituitary Flashcards
What kind of hormones are released from the anterior pituitary?
FLAT PIG
FSH, LSH ACTH, TSH, PROLACTIN, GH
What directly regulates the release of anterior pituitary hormones?
Hypophysiotropic neuropeptides
How are hypophysiotropic hormones transported to the anterior pituitary?
They are released in the median eminence and travel down the long hypophysial portal veins
What produces the overall rhythmic patterns of pituitary hormone release?
The interaction of sleep and circadian effects
What are the three categories of anterior pituitary hormones?
Glycoproteins,
Proopiomelanocortin-derivatives,
GH and prolactin family
What are the anterior pituitary glycoprotein hormones?
Thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH)
What is the general structure of the glycoprotein anterior pituitary hormones?
What part confers the biological specificity of each hormone?
Alpha subunit shared by all of the glycoprotein hormones and unique beta subunit that confers the physiologic effect
What cells produce proopiomelanocortin?
Corticotrophs of the anterior pituitary
What hormones are derived from proopiomelanocortin?
Adrenocorticotropic hormone, beta-endorphin, and melanocyte stimulating hormone
Approximately what percentage of the anterior pituitary produces growth hormone?
At least 50%
What hormone stimulates production of thyroid-stimulating hormone?
What cells produce that hormone?
Thyrotropin-releasing hormone;
predominantly parvicellular neurons in the paraventricular nucleus
On what cells does thyrotropin-releasing hormone act? To what type of receptor does it bind?
Anterior pituitary thyrotrophs;
GPCRq (inc. PLC)
What hormone stimulates production of follicle-stimulating and luteinizing hormones?
On what cells does that hormone act?
To what type of receptor does it bind?
Gonadotropin-releasing hormone;
anterior pituitary gonadotrophs;
GPCRq (inc. PLC)
What hormone stimulates production of adrenocorticotropic hormone?
On what cells does that hormone act?
To what type of receptor does it bind?
Corticotropin-releasing hormone;
anterior pituitary corticotrophs;
GPCRs (inc. AC)
On what cells does somatostatin act?
To what receptor?
What is the effect?
Somatotrophs;
GPCRi (dec. AC)
inhibition of growth hormone release
On what cells does Growth-hormone-releasing hormone act? To what receptor? What is the effect?
Somatotrophs;
GPCRs (inc. AC);
release of growth hormone
How does dopamine regulate prolactin release?
Dopamine binds to dopaminergic GPCRi receptors, decreasing adenylyl cyclase activity, increasing potassium channel activation and inhibiting calcium channels to overall inhibit prolactin release
Which isoform of growth hormone is most important in terms of physiologic function
22 kDa isoform
What is the half-life of growth hormone?
20-30 minutes
When is growth hormone released?
During slow-wave sleep, post-prandially, and during exercise
At what point of development is growth hormone released in its highest levels?
Peak during adolescence
How does blood glucose level affect growth hormone release?
-low blood glucose stimulates growth hormone
(ultimate goal is to increase blood glucose: GH inhibits insulin receptor => increasing blood glucose)
GH release is stimulated by severe hypoglycemia and suppressed by high spikes in hyperglycemia
What compounds can stimulate GH release? What can suppress it?
(+) GHRH, Ghrelin, ACh, alpha-adrenergic agonists, dopamine, serotonin;
(-) Somatostatin and IGF-1
What is the receptor for growth hormone?
Where is it expressed?
Receptor associated kinase;
liver, bone, muscle, adipose, kidney, brain, heart, and immune cells
How does GH affect the liver?
Stimulates production and release of Insulin-like growth factor 1
How does GH affect the muscle?
Stimulates protein synthesis; stimulation of IGF1 synthesis
How does GH affect the bone?
Increases collagen synthesis, increases cell size, and number and increases longitudinal growth ; stimulation of IGF1 synthesis
How does GH affect adipose tissue?
How does it affect glucose utilization?
Stimulation of lipolysis (inhibits lipoprotein lipase, stimulates hormone sensitive lipase);
Muscles will take up the hydrolyzed fatty acids and so there will be more glucose available in the blood
Where is IGF1 produced? How does it circulate?
Liver, muscle, bone; circulates bound to a protein
What are the effects of IGF1?
Increased DNA, RNA, protein synthesis–> growth
To what kind of receptor does IGF-1 bind?
What subunits make up the structure and what is the function of each subunit?
Binds to a ligand-activated receptor kinase;
Consists of the alpha subunit (binds to hormone) and the beta subunit (tyrosine kinase activity)
What is Laron syndrome?
How does it present?
How does it affect IGF-1?
An autosomal recessive disorder characterized by insensitivity to GH due to a variant of GH receptor; Presents with short stature and resistance to diabetes and cancer;
Impairs IGF-1 release
How does a GH deficiency present in childhood?
How is the diagnosis made?
Decreased linear growth– short stature;
Height below 2 SD below average
How does GH-deficiency affect infants?
GH-resistance?
Deficiency- low birth weight;
resistance- low birth length and weight
How does a GH deficiency manifest in adulthood?
Decreased GH release and pulsatility is associated with aging, cancer and HIV and is associated with increased cardiovascular risk and loss of muscle mass
How does a growth hormone excess present in children and in adults?
What is the most frequent cause?
Children- gigantism; adult- acromegaly; Piuitary adenoma
How can a GH deficiency be evaluated through GH stimulation tests?
Challenging with either insulin and GHRH to measure the increase in growth hormone elicited
What is the main mechanism by which prolactin is increased in pregnancy?
Increased estrogen stimulates the growth and replication of lactotrophs
What are the physiologic effects of prolactin? What physical stimulus results in prolactin release?
Breast differentiation, duct proliferation and branching, glandular tissue development, milk production and lactogenic enzyme synthesis; Suckling
How is the release of prolactin regulated? What other compounds are required for prolactin to have full effect?
Prolactin release is predominantly under tonic inhibition by hypothalamic dopamine release and is additionally inhibited by somatostatin and GABA and can be stimulated by several factors; requires insulin and cortisol to be normal in circulation
How does prolactin affect its own production?
Prolactin increases dopaminergic inhibition of prolactin release (negative feedback loop)
What is the only hormone solely under hypothalamic inhibitory control by dopamine?
Prolactin
How can a prolactinoma cause infertility and gonadal dysfunction?
High levels of prolactin can inhibit GnRH release, which lowers LH and FSH and so gonadal steroidogenesis will decrease leading to amenorrhea, impotence, and decreased libido
During pregnancy, what keeps the action of prolactin in check?
High progesterone levels in the breasts
(L3 - Anterior Pituitary) On a hot, sunny day:
A) ADH release would be lowest at noon
B) aquaporin 1 expression would be stimulated at noon
C) AVP signaling would involve PKA activation
D) Urine osmolality would be unaffected by ADH release
C) AVP signaling would involve PKA activation
- ADH released from bloodstream
- binds to V2R (alpha Gs)
- increase AC, cAMP, PKA
- PKA phosphorylates aquaporin 2
- aquaporin 2 releases on apical side
- allowing water inside collection duct to pass via aquaporin 3, 4 on basolateral side to enter the bloodstream
(L3 - Anterior Pituitary) Laceration of the median eminence would result in:
A) increased release of all pituitary hormones
B) decreased release of hypothalamic peptides
C) increased release of prolactin
D) decreased release of all pituitary hormones
C) increased release of prolactin
Prolactin is under negative control via dopamine via hypo-physio-tropic control
*laceration of median eminence would not decrease RELEASE of hypothalamic peptides, but would DECREASE DELIVERY
What is the relationship between GH and glucose storage?
As you increase GH, decrease glucose storage => releasing glucose into bloodstream to be used for energy
(L3 - Anterior Pituitary) TRUE/FALSE? Laron Syndrome is associated with low levels of IGF-1.
TRUE
Laron’s disease - GH activity deficiency
- GH receptor insensitivity (mutated receptor)
- GH stimulates IGF-1 production in liver
- GH is not binding to its receptor, IGF-1 not being produced => lower levels of IGF-1
