Lecture 1 - Endocrine Introduction

Objectives:

Definition of Endocrinology:

Study of _____ chemical adjustments and other activities accomplished by hormones

Endocrine glands are scattered throughout the body and secrete _____

Endocrine glands and their targets are not connected _____, but are connected by the hormones that they secrete

Endocrine glands function in an endocrine sense, but can have other functions as well

______ function involves the secretion of chemicals into ducts or passageways connected to the ____ environment (body surface, digestion)

Endocrine System Basic Schematic

Endocrine System

–____ glands

–____ target cells
•Dependent on ____
(H -> H+R -> final effect)

•Overall functions:

–Regulate organic metabolism
–Regulate H20 and electrolyte balance
–Induce ∆s to help body cope with stresses
–Promote growth and development
–Control reproduction
–Regulate RBC production
–CV and GI control/integration

* “__ and __” Concept

Nervous System VS. Endocrine System

Nervous system is "___" system
-___ arrangement b/w neurons & target cells
-___ released into synaptic cleft
-Very __ distance (diffuses across synaptic cleft)
-dependent on ___ anatomical relationship b/w neurons & their target cells
-Generally ___ response
-___ duration of action
-Coordinates ___ , ___ resposnes

Endocrine system is a "___" system
-endocrine glands __ structurally related to one another OR target cells
-_____ released into the blood
-____ distance (carried by blood)
-dependent on ___ of target cell binding & responsiveness to a particular hormone
-Generally ____ repsonse
-___ duration of action
-Controls acititvities that require ____ ___ rather than speed

INdirect Intracellular Communication

Paracrine: ___ acting
Ex. Histamine (blood vessel dilation)

Hormones: ___-range
Ex. Ant. Pituitary hormones

Neurotransmitters: Very ____-range
Ex. NE on pancreas β-cells

Neurohormones: (____)
Ex. Gonadotropin Releasing-Hormone
*happens a lot with brain & pituitary

Intracellular Communication

___ ____ – process by which incoming signals are conveyed to the target cell, where they are transformed into the dictated cellular response.

Occurs by different mechanisms depending on chemical messenger and receptor type

Mechanisms:
1)Opening or closing ___ gated receptor-channels

2)Activating receptor-enzymes (receptor functions as an ___)

3) Activating second messenger pathways via ____ receptors

4) Binding to receptors to ___ change gene activity

Intracellular Communication - Signal Transduction

1) Opening or closing chemically gated receptor-channels

Receptor serves as ___
-Can open or close (___ or ___)

General STEPS:
extracellular messenger binds -> binding leads to opening of receptor -> ions enter -> ions lead to cellular response

Intracellular Communication - Signal Transduction

2) Activating receptor-enzymes (receptor functions as an ___)

*Protein ___ – any enzyme that transfers a phosphate (PO4) group from ATP to an intracellular protein

Protein kinases are altered in two ways:
1 – ___ kinase

2 – ____ Receptors

Intracellular Communication - Signal Transduction

2) Activating receptor-enzymes

General STEPS for Tyrosine kinase pathway:

extracellular messenger binds to receptor -> binding activates protein kinase -> protein kinase activates specific protein -> active protein leads to cellular response

*Receptor itself acts as an ____

Intracellular Communication - Signal Transduction

3) Activating second messenger pathways via ____ receptors

General STEPS for GPCR pathway:
extracellular (1st) messenger binds to receptor -> Receptor activated G protein -> G protein alpha subunit activates effector protein -> effector protein makes 2nd messenger -> 2nd messenger activates protein kinase -> Protein kinase activates specific protein -> Active protein leads to cellular response

Turned off by _____, which are usually continuously active

->Extracellular messenger is released to be degraded or excreted or the ligand-receptor complex can be internalized and degraded.

*EX: ____ hormones

REVIEW

Endocrine vs. neural communication:
->non-connected vs. structurally connected ->long vs. short distance of acton
->brief action vs. long-lasting action
->neurotransmitters vs. hormones
->precision vs. duration

Indirect types of cellular communication:
->paracrine hormones
->neurotransmitters
->neurohormones

Types of receptors:
->Chemically gated receptor channels
->Activating receptor enzymes
->Activating second messenger pathways (hydrophilic)
->Internal receptors that change gene activity (lipophilic)

Hormone classifications

1) Hydrophilic:
-> ___ water solubility

->___ fat solubility

a) Peptides
•___ chains of amino acids
–Ex. Oxytocin

•Can be long -> Protein range
–Ex. Growth hormone

b) Glycoproteins
–_____ conjugated to protein
•Ex. Follicle Stimulating Hormone (FSH), Luteinizing Hormone(LH)

Hydrophilic PEPTIDE hormone synthesis:

Same steps as for any protein:
1. Preprohormone in rough ER

2. Migrate to golgi in transport vesicles during which they are cleaved to the mature hormone sequence.

3. Golgi complex packages them into secretory vesicles

Hydrophilic peptide hormone secretion and transport:

–>Storage
•In ___

->Secretion
•Occurs upon specific stimuli
•____ release

–Transport
•Dissolved in ____

OTHER Hydrophilic Hormones

Amines
-Amino-acid derivatives

Catecholamines: made from ____
->Secreted from the __ ___

Indoleamines: made from ____
->Secreted from the ___ ___

**Storage and secretion the same as peptides.
BUT 50% of catecholamines are bound to ____ for transport

Hydrophilic Hormone Mechanisms of Action

Cyclic AMP Pathway

Adenyl cyclase = ____ protein

Adenyl cyclase -> cAMP (__ ____) -> protein kinase A -> activates protein & gets cellular response

Hydrophilic Hormone Mechanisms of Action

IP3-Ca2+ Pathway

_____ = effector protein

Phospholipase C -> IP3 -> Ca2+ (__ ___) -> calmodulin -> cellular response

Also get:
Phospholipase C -> DAG (2nd messenger) *NOT ___ soluble -> activates protein -> cellular response

Hydrophilic Hormone Mechanisms of Action

Minute quantity for overall effect
–Multiple steps

This know as _____?

Hormone classifications Continued ...

Lipophilic (__ loving)
- ___ Soluble
(do NOT like aqueous environ. but DO like ___ ___ and nucleus)

1. Steroids
->Cholesterol derivatives
(Ex. Estrogen, testosterone, cortisol, aldosterone)

2. ____ Hormone
Made from Tyrosine (like ____)
->But has 2 tyrosine amino acids
->T4 = has 4 iodines
->T3 = has 3 iodines

Lipophilic Steroid Hormone Synthesis

Synthesis begins with common precursor followed by a series of enzymatic steps

Some ____ may occur once secreted into blood or upon arrival at target organs
(Ex: Testosterone to Estradiol)
(EX: Also true for Thyroid Hormone T4 -> T3)

***THE TYPE(S) OF STEROID HORMONE(S) THAT A TISSUE MAKES DEPENDS UPON ITS COMPLEMENT OF ____!***

Lipophilic Hormone Storage, Secretion, & Transport

–Storage
•__ stored
–If formed, immediate diffusion

–Secretion
•Dependent on ___ of synthesis
–Reminder: Some ___ may also occur in blood/tissues
[Ex: T -> E2 (also T4 to T3)]

–Transport
•____ bound to plasma proteins
(Specific binding protein OR ___)

•Only ____ hormones (small fraction of total) free to bind to receptors

*Catecholamines – 50% bound, 50% free

Lipophilic Hormone Mechanisms of Action

•Most act through ___ activation
–Specific hormones have specific hormone response ___

(EX: the estrogen-estrogen receptor complex binds to the estrogen response element)

Some (i.e. __ steroids)
can bind to membrane-bound receptors to evoke __-gene-activating activities

Determinants of Plasma Hormone Concentration

1) Metabolism
•Activation/conversion
(Ex: Thyroid Hormone)
–T3 __ ___ than T4

2) Plasma protein binding
(Ex. Lipophilic hormones)
–___ H is monitored

3) Metabolic inactivation
•Liver, kidney, blood, target cells __ hormone

4) ___ rate
•↑ release -> ↑ [H]

REVIEW:

Hydrophilic vs. lipophilic hormones

->protein synthesis machinery vs. enzymatic (modification of cholesterol)

->Secretory granules and stimulus vs. release upon synthesis

->Freely moves in blood vs. specific transport proteins

->Cell membrane receptors vs. nuclear actions via a HRE

Determinants of Plasma Hormone concentrations:

->Secretion rate
->Metabolism
->Plasma binding proteins
->Metabolic inactivation