Physiology Block 3 Week 14 07 Intro to Pituitary Flashcards
Classic Hormone Groups
Tyrosine Derivatives
Steroids
Peptides/proteins
The class of hormone determines the mechanism of?
Synthesis and Secretion
Transport in the plasma compartment (protein binding)
Mechanisms and speed of onset of action (membrane receptors vs intracellular receptors)
Metabolism (half-life and metabolic clearance rate)
What are hormones?
Chemicals that are released through ductless glands and affect somewhere
Thyroid Hormones
% bound to plasma proteins
Half-life
Clearance
VERY high % binding to plasma proteins (99.95%)
Biologically active
VERY long half-lives
–Only free (dissolved) hormone can bind to receptor
LOW metabolic clearance
Steroid Hormones
% bound to plasma proteins
Half-life
Clearance
HIGH % binding to plasma proteins (94%)
LONG Half-life
Low Metabolic Clearance
Peptide and Protein Hormones
% bound to plasma proteins
Half-life
Clearance
ONLY circulate free form
SHORT Half-life
HIGH metabolic clearance
Exception = insulin-like growth factors
Endocrine Rhythms
Circadian
Ultradian
Stimulus-Induced
Seasonal
Circadian Endocrine Rhythm
Around the 24 hour clock
Test testosterone at morning when should be the highest
Ultradian Endocrine Rhythm
High frequency and Regular Bursts
Pulsatility of Luteinizing Hormone
Stimulus-Induced Endocrine Rhythm
Ex. Breast feeding is stimulus for increased prolactin
Seasonal Endocrine Rhythms
Ex. Vitamin D
Negative Feedback of Glucagon and Glucose
Glucagon is to prevent hypoglycemia
The alpha cells of the endocrine pancreas (produces glucagon) have glucose sensors that detect a decrease in EC glucose
- ->increases glucagon release
- ->stimulates hepatic gluconeogenesis and glycogenolysis
- ->increased release of glucose form the liver restores blood glucose
Increased blood glucose inhibits alpha cells from producing glucagon
Parallel to Insulin
Negative Feedback of Insulin and Glucose
Insulin prevents hyperglycemia
An increase in blood glucose is sensed by the beta-cells of the endocrine pancreas
- ->increases insulin release
- ->insulin inhibits glucose release from the liver
Parallel to Glucagon
G-Protein Coupled Receptors Mechanism
Hormone activates the receptor
Inactive alpha, beta, and gamma G protein complex associates with the receptor and is activated
–exchanges GDP for GTP
Alpha unit dissociates and interacts with membrane-bound target proteins (Adenylyl cyclase)
Generation of second messengers!
G-Protein coupled generation of second messengers
FAST–Epi or ACTH
Cyclic adenosine monophasphate (cAMP) released in exchange for ATP
cAMP activates cAMP dependent Protein Kinase (PKA)
Phosphorylates proteins leading to a cellular response
G-Protein coupled to PLC, IP3, DAG second messenger system
Peptide hormone binds to receptor
Activates G-protein
Activates Phospholipase C
Splits PIP2 into DAG and IP3
IP3 exerts function on endoplasmic reticulum
- release of Ca2+ leads to cellular response
- release of inactive enzyme
DAG moves into cytoplasm and activates Protein Kinase C (PKC)
Phosphorylates inactive enzyme leading to cellular response
Lipophilic Hormones
SLOW–Cortisol
Steroids with intracellular receptors in target cells
Hormone binds to receptor in cytoplasm or in nucleus
Hormone-Receptor complex binds to hormone response element (promoter) on DNA
–Either activates or inhibits gene transcription, formation of mRNA, and protein synthesis
Mechanism of action of Thyroid Hormones
Nuclear Receptor
Thyroxine (T4) secreted from thyroid gland
Activated to T3 (by monodeiodinase) in cytosol and binds intracellular receptor, which binds promotoer
–allows a target tissue to regulate how much thyroid hormone action to which it is exposed
Ex. Heart can express the enzyme to convert T4 to T3
Ex. Inhibitors to prevent conversion as well
Pituitary Gland
Anterior Pituitary:
- Pars distalis
- Adenohypophysis
Pars Intermedia
Posterior Pituitary
-produces anti-diuretic hormone (vasopressin) and oxytocin
Hangs off base of brain by hypophysial stalk (infundibulum)
Neurons with cell bodies in the hypothalamus synthesize releasing or inhibitory (hypophysioTROPIC) factors and release them from short axons that terminate on capillaries in the median eminence
Forms portal veins that drain onto the anterior pituitary carrying hypophysiotropic factors
These factors stimulate or inhibit the release of anterior pituitary hormones that exit the pituitary via veins that drain into the petrosal sinuses and then jugular veins
Classes of Anterior Pituitary Hormones
Glycoproteins
Growth Hormone/Prolactin
POMC
Gylcoproteins
Anterior Pituitary Hormone
TSH, FSH, LH–stimulate synthesis
Identical alpha subunits
Beta subunit conveys receptor binding specificity
Growth Hormones/Prolactin
Anterior Pituitary Hormone
Promotes growth in stature and mass
Milk secretion
Amino Acid sequence homology
POMC
Anterior Pituitary Hormone
POMC gene produces a peptide (POMC) that is post-translationally modified to ACTH
Promotes synthesis and secretion of adrenal cortical hormones
Hypophysiotropic Hormones
Hypothalamic releasing or inhibiting hormones
Corticotropin Releasing Hormone Gonadotropin Releasing Hormone Growth Hormone Releasing Hormone ****Somatotropin Releasing-Inhibiting Factor (inhibits GH secretion) Prolactin Stimulating Factor ***Prolactin Inhibiting Factor--Dopamine Thyrotropin Releasing Hormone
Anterior Pituitary
Master gland
Controls:
- thyroid function (TSH)
- pre-pubertal growth
- adrenal cortex (ACTH)–release of adrenocortical hormones, gonadotropins (FSH and LH), and prolactin
Pituitary Descending Stimulation
Input to hypothalamus (environmental factors) increases or dec hypophysiotropic factor release
Hyopphysiotropic factor stimulates anterior pituitary to produce a tropic hormone
Stimulates a target gland to produce a final factor
Pituitary Control Feedback Loops
Long-Loop:
Target gland produces Target Gland Hormone
-serves as negative feedback on pituitary or hypothalamus
Ex. Cortisol increases and will shut off ACTH release
Short-Loop: Pituitary hormone (tropic hormone) serves as negative feedback on hypothalamus
Trophic Effect
SLOW–growth effect over days and weeks
Nurturing/growth promoting effect
If ACTH high for a long time, stimulates adrenal growth and hypertrophy
If Low ACTH leads to adrenal atrophy
Tropic Effect
FAST–Immediate response
Acute stimulatory effects
ACTH stimulates cortisol release within minutes
Which of the following has the longest half-life?
Growth Hormone
Arginine Vasopressin
Testosterone
Angiotensin 2
Testosterone
Steroid Hormone, binds plasma protein
Want increase in Prolactin
Pregnancy, pituitary gets big, lots of prolactin produced
Dopamine inhibits prolactin–want to dec dopamine
Suckling inhibits the nerves in the hypothalamus that make dopamine
Dopamine goes down, releasing lactotroph, allowing prolactin to inc
Hypopituitarism
Too little pituitary function (anterior)
How do you treat a pituitary tumor?
Pituitary tumors express receptors for hyphysiotropic hormone that controls it
Give dopamine agonist–shrinks the tumor
Which of the following will lead to a decrease in prolactin secretion?
Dopamine Agonist
Dopamine Antagonist
Post-Partum Nursing
Pregnancy
Dopamine Agonist turns on dopamine, inhibiting lactotroph release of prolactin
