Hypothalamus, Pituitary, Thyroid Flashcards
Neurosecretory Cell
Neuron that acts as an endocrine cell and produces neuropeptides.
What do hypothalamic neuropeptides do? How are they transported?
They are transported through the hypothalamic pituitary portal system to the anterior pituitary, where they cause AP hormone release.
Lactotrophs, Somatotrophs, Gonadotrophs, Corticotrophs, Thyrotrophs
Release: Prolactin, GH, LH and FSH, ACTH, and TSH.
Posterior Pituitary hormones
Vasopressin and oxytoxin. Stored in PP, made in hypothalamus.
3 Hormone Classes
Peptides, Amino acid derivatives, Steroids. Most hormones are peptides. Only steroids like cortisol are lipid soluble and bind to intracellular receptors.
What do FSH, GH, LH, Prolactin, TSH, ACTH, and Vasopressin stimulate?
Ovary (estrogen), liver (IGF-1), testicles (testosterone), breasts (milk), Thyroid (thyroxine), adrenals(cortisol), kidneys (hold onto water). Products in parentheses negatively feedback onto initial hormone.
Examples of endocrine positive feedback
Breast feeding causes additional prolactin release. Ovulation causes increases in estrogen.
Hypothalamic inhibitory neuropeptides
Somatostatin (stops GH), dopamine (stops prolactin).
What creates a target cell?
Presence of receptors
Explain:
When GnRH is given continuously, receptors downregulate and cause less release of LH and FSH
Which hormone’s circadian rhythms does this represent?
Cortisol
What hormone does this represent?
Testosterone
Why are prolactin and growth hormone so similar?
They are in the same gene family. Both use Jak/Stat pathway.
Jak Stat Pathway
Tyrosine-kinase associated receptors. Binding of substrate causes dimerization and phosphorylation of Jak and STAT. STAT moves into the nucleus and acts as a transcription factor to upregulate certain genes of increased growth and metabolism.
Ghrelin. How does it work?
Produced by stomach, activates NPY neurons and activates the pituitary. Associated with hunger. Works by stimulating growth hormone release.
Direct Actions of Growth Hormone
Are counter-regulatory to insulin. GH increases gluconeogenesis and lipolysis. GH also activates IGF-1, which uses GH’s breakdown products to create stuff.
Stimulators and inhibitors of GH
Stimulators: Exercise and Puberty, Ghrelin
Inhibitors: Obesity and advanced age.
Indirect actions of GH
All through IGF1. IGF1 is a growth factor for muscle and bone. In bone, it stimulates osteoblasts and inhibits osteoclasts.
Why is Regulation of Prolactin Unique?
Because it’s mostly tonic inhibition by dopamine released from hypothalamus. This inhibition is overcome in pregnancy and breast feeding. Prolactin causes milk production.
Where is the thyroid located?
Wrapped tightly around the trachea below the cricoid cartilage.
How is the thyroid stimulated?
By TSH from anterior pituitary.
Thyroid Feedback Mechanism
TRH from hypothalamus stimulates TSH from AP, which stimulates T4/T3 release from Thyroid gland.
T4/T3 negatively regulate AP activity.
How are TSH, HCG, LH, and FSH related?
They are part of the same hormone family. They are all glycoproteins (protein w/carbohydrate antenna).
TSH, FSH, LH, HCG structure
All have identical alpha subunit, unique beta subunit that conferrs specificity for their individual receptors.
HCG
Secreted from chorion in pregnancy. Very high levels of HCG can stimulate the TSH receptor, causing T3 and T4 release. Sometimes an HCG secreting tumor can cause hyperthyroid-like symptoms.
TSH glycosylation
In order to function correctly, TSH must be glycosylated. However, our assays are not sensitive enough to determine if TSH in the blood is glycosylated correctly, so it often goes undetected. So, we measure improperly glycosylated TSH in blood.
What does TSH do when it binds its receptor?
Induces hormone synthesis and secretion. Also stimulates thyroid cell growth and differentiation.
T3 and T4
T3 (triiodothyronine)- 20% of Thyroid secretions. Can be created by T4 in tissues via peripheral conversion. Very potent.
T4 (Thyroxine)- 80% of thyroid secretions. Circulating precursor. Long half-life.
Peripheral Conversion. How does it occur?
The process of converting T4 to T3 in tissues. 75% of T3 is created this way.
Type I and Type II deiodinases remove one iodine from the outer iodine to create T3.
Type III deiodinases will create rT3 by removing the inner iodine.
Thyroid Follicle Structure
Sits next to blood vessel, follicular epithelial cells surround lumen (colloid).
Thyroglobulin (T3 and T4 synthesis)
A carrier molecule with attached tyrosines made in follicular epithelial cells. Once transported into colloid, will pick up Iodine (I2) to make DITs and MITs on surface. Transported back into epithelial cell, releases DIT and MIT, and is recycled. DIT+DIT = T4, DIT+MIT=T3.
How is iodide transported into the follicular epithelial cell?
Via a Na-I cotransporter.
What do DIT and MIT stand for?
Diiodotyrosine, monoiodotyrosine.
Radioactive Iodine
Can take a picture of thyroid, destroy thyroid tissue, or treat thyroid cancer.
Wolff-Chaikoff Effect (High doses of Iodine)
High doses of Iodine will down-regulate Na-I cotransporter, so less I is pumped into colloid. Less T3 and T4 made. Treats hyperthyroidism.
TBG
Thyroxine-binding globulin. 99.97 of T4 circulates bound to TBG.
Once T3 is in the cell, what happens?
Binds to nuclear receptor which brings it inside, binds to DNA, acts as a TF.
Effect of T3 and T4.
Growth- Bone and cells
CNS- Maturation
BMR- Increase Na-K pump, increase O2 consumption, increase heat production, increase BMR
Metabolism- Increased glucose absorption, increased glycogenolysis, increased gluconeogenesis, increased lipolysis
Cardiovascular- Increased cardiac output, Cholesterol regulation
Thyroid hormone effect on cholesterol
Promotes bad cholesterol excretion, and increases HDL levels.
Why does paleo diet increase cholesterol?
Resembles starvation, which lowers thyroid hormone levels.
Thyroid Hormone effects on vasculature and kidney
Promotes vasodilation, increase of RAAS system, which promotes sodium reabsorption and increase in blood volume.
In kidney, increases sodium reabsorption.
In heart, increases inotropy and chronotropy, increases BP.
INCREASES GFR.
