Hypothalamus and Pituitary Gland Flashcards
Neurohypophysis origin
Downward evagination of the floor of the primitive brain; composed of neurons
Posterior Pituitary Neurons
Magnocellular neurons that originate from the supraoptic and PVN nuclei that terminate near the capillary beds of the pituitary
Synthesis of posterior pituitary hormones
Synthesized in the cell bodies of neurons and transported to the posterior pituitary in a secretory granule w/ neurophysin (chaperone)
Secondary Capillary Plexus
Receives tropic hormones from the hypothalamus that were secreted into the hypothalamophyseal portal system
Somatotrope
Releases GH
Activated by GHRH
Inhibited by SS
Thyrotrope
Releases TSH
Activated by TRH
Lactotrope
Releases PRL
*Inhibited by dopamine; otherwise would secrete constantly
Slightly stimulated by TRH
Gonadotrope
Secretes FSH and LH
Activated by GnRH
Corticotrope
Releases ACTH, y-LPH, and B-endorphin
Activated by CRH and AVP
Gs activating Releasing Hormones
GHRH and CRH
Gi-mediated Releasing Hormones
SS and Dopamine
Gq-mediated Releasing hormones
TRH, GnRH, AVP
Glycoprotein family
Consists of FSH, LH, TSH, and hCG
a-subunits all the same; b-subunits are what makes them different
*All act by increasing cytosolic cAMP
Somatommamotropin family
Consists of GH and PRL (acidophiles) and single chain proteins connected by interacting S-S bonds
*Also includes placental hGH, hPRL, and hSS
POMC family
Cleavage of product from POMC gene can form ACTH, y-lipotropin, and B-endorphin
*Alternate cleavage produces a-MSH instead
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GH binding protein
Formed from the cleavage of GH receptor on the external surface of target cells, therefore, it easily reacts w/ the receptor
Direct actions of GH
*Actions are diabetogenic
Stimulates IGF-1 production in the liver
Stimulates lipolysis in adipose => Increased FFAs
Inhibits glucose uptake in adipose and skeletal muscle
Decreases insulin sensitivity of tissues
Increase lean body mass (increased protein synthesis; decreased urea nitrogen)
GH Receptor Action
GH binding induces dimerization of the JAK receptors and autophosphorylation of their intracellular tyrosine residues
=> STATs bind via SH2 domains, form dimers, and migrate to the nucleus to promote genetic transcription
IGF-1 source
Mostly the liver, however, prechondrocytes also express GH receptors and will increase production of IGF in response to stimulation
Circulating IGF-1
Bound to a complex including IGFBP-3 and an acid-labile unit
*Fnxns to provide a circulating reservoir and increase the T 1/2 of IGF-1
IGF-1 Mechanism of Action
Binds to a receptor TK causing the autophosphorylation of 3 receptors leading to activation
=> IRS binds via SH2 domains and activates signaling cascade
- Also activates the MAP/Kinase pathway to induce gene transcription
- IGF-1 is similar to proinsulin and activates a similar receptor => high concentrations of IGF-1 will mimic insulin actions
Target cells of IGFs
Fibroblasts, Chondrocytes, Adipocytes, Muscle Cells
Stimulates: cell proliferation, protein synthesis, insulin-like effects
Ghrelin
Enhances the activity of GHRH on the anterior pituitary
=> Opening of Ca2+ channels causing depolarization and release of secretory vesicles
SS Action on Somatotrope
By using the Gi pathway, opens K+ channels causing hyperpolarization of cell
Negative Inhibition of GH
Exhibited primarily by IGF-1 on the hypothalamus; GH also inhibits its own release at the hypothalamus
Stimulators of GH Secretion
Normally occurs 1-2 hours after onset of deep sleep but also with:
Stress
Exercise
Post-prandial hypoglycemia
Sex Androgens
Ghrelin
Fasting effects on GH
48 hours => Increased GH, unchanged IGF-1
Prolonged fasting => Increased GH, decreased IGF-1
*IGF-1 production in the liver requires adequate nutrition causing this decrease, however, IGFBP-3 will still be made
Prenatal Growth factors
- Genetics
- Placenta (weight directly weighted to birth weight)
- Maternal environment (Smoking and Alcohol cause MR and birth defects)
- Hormones (IGF and IGFBP levels are directly correlated to birthweight; insulin also important in tissue uptake of nutrients)
Postnatal Growth
Stabilizes by age 2; spikes again at the onset of puberty as well as GH levels
Principal extrinsic regulator of post-natal growth
Adequate nutrition
Principal hormone regulating growth
GH; duh
- Actions are mediated by IGF-1
- T3 acts synergistically w/ GH by promoting GH secretion and IGF-1 production; w/o it, growth will be stunted
Treatment of hypothyroid children w/ thyroxine
Effects on growth will show increased GH secretion w/ a rapid catch-up phase
*Hyperthyroidism causes child to grow fast; but not larger
Growth spurt @ puberty
Primarily mediated by sex steroids; promote linear growth and maturation of epiphyseal plate
Estradiol
Principal hormone that binds to the epiphyseal plate in BOTH boys and girls; binds to receptors on epiphyseal growth plate stimulating growth and closure
Aromatase
Enzyme responsible for converting testosterone into estradiol in males
*Boys defective in aromatase will continue to grow after the normal age for growth spurt since estrogen will not close the epiphyseal plates
Testosterone on developing males
Increases periosteal bone expansion and muscle growth
Insulin effects on growth
Promotes protein anabolism; hyperinsulinemic children grow excessively
Glucocorticoid effects on growth
When present in excess, will limit growth
*After removal, catch-up growth occurs but is not complete
Laron Dwarfism
GH receptor defects; pts. will have increased GH but no IGF-1 production
GH deficiencies
Produce dwarfism, delayed puberty, tendency towards hypoglycemia, mild obesity
Adenohypophysis Origin
Upgrowth of ectodermal cells from the primitive pharnyx; composed of epithelial tissues
Fetal IGF-1
U correlated w/ GH secretion; directly correlated to birthweight
