UNIT 1 HORMONES IN ACTION

TH cascade start

Stimulus

TH - Stimulus

Hypothalamus

TH- Hypothalamas

Thyrotropin releasing hormone TRH

TH - TRH

Anterior pituitary

TH- Anterior Pituitary

Thyroid Stimulating Hormone TSH

TH- TSH

3rd Endocrine Gland

TH- 3rd Endocrine Gland

Thyroid Hormone

TH- Thyroid Hormone

Target cell

Major cause of hypo function

Autoimmune disorder or hormone resistance

Hyper function major cause

Tumor

Types of Hormones

Peptide, Steroid, Tyrosine derived

Largest family of hormones

Peptide

How are Peptide Hormones secreted

Exocytosis

Peptide Hormones are

Hydrophilic

Steroid hormones are

Hydrophobic

Specificity

Ability to bind only one hormone

Affinity

Strength the receptor binds

Agonist

Binds to receptor and triggers response

Antagonist

Binds to receptor and doesn’t trigger a response

Up/Down regulation

Alteration in the number of receptors

Two functional domains on a peptide receptor

Recognition domain, Signaling Domain

Cell Surface receptors

G protein coupled receptors, tyrosine kinase receptors

Intracellular Receptors

Steroid Hormone Receptor

Short term regulation (2 ways)

Allosteric regulation and covalent modification

Allosteric regulation

Effector binds to enzyme, immediate effect, changes affinity for substrate, rate of reaction

Covalent Modification

Phosphorylation/dephosphorylation, seconds to minutes

Long term regulation

Gene expression, hours to days, alter amount of enzyme by altering rate of transcription or translation

Peptide hormones are secreted

On demand

Steroid Hormones are secreted

When they’re made

Peptide hormones half life

short

Steroid Half Life

Long

GPCR transducer

G protein

GCPR effector

PLC

GPCR Second Messengers

IP3, DAG, Ca2+

Calcium signaling

4 calcium molecules bind to calmodulin and cause a conformational change

Activation of PKA Transducer

G protein

Activation of PKA effector

Adenylate Cyclase

Activation of PKA second messenger

cAMP

Steroid Hormones are ____ derived

Cholesterol Derived

Cholesterol is from

Diet, synthesis

Steroid Hormone Receptor functional domains

Hormone-binding domain, DNA binding domain, Activation domain, Protein interaction domain

Location of Steroid Hormone receptor

Intracellular

Location of Peptide Hormone receptor

Cell surface

Class 1 steroid superfamily

In resting state zinc fingers are covered by inhibitory protein, predominately in cytosol, receptors dimerize and bind to DNA

Class II Steroid Superfamily

In resting state bound to DNA. predominantly in nucleus, may inhibit or silence basel gene transcription, recruit co repressor

Tyrosine derived Hormones

Epinephrine and Thyroid Hormone

Epinephrine is ____

Peptide-like

Epinephrine is synthesized in

Adrenal Medulla

Epinephrine has what kind of receptors

Plasma membrane receptors -GPCR

Epinephrine is secreted

On Demand

Epinephrine receptors are called

adrenergic receptors

Thyroid Hormone is synthesized in

Thyroid gland

Thyroid hormone is secreted

When made

Thyroid Hormone receptors are called

Thyroid Hormone Receptors

Somatotroph

Secrete Growth Hormone in AP

Corticotroph

Secrete ACTH in AP

Posterior Pituitary releases

Antidiuretic Hormone, Oxytocin

Somatostatin

GHR inhibitory hormone

Growth Hormone is highest during this part of day

When Sleeping

GH is highest in this part of life

Puberty

GH goes to liver

Increase gluconeogenesis and Produce IGF-1

GH goes to adipose

Increase lipolysis

IGFs

Increase somatic cell and bone growth

GH affects muscle

Increase amino acid uptake and protein synthesis

Increase gluconeogenesis

Increase blood sugar

Somatostatin

inhibits secretion of growth hormone

Negative feedback on GH

Increased IGFs and Blood Glucose

JAK2

Phosphorylate each other and activates JAK2’s kinase activity

GH binds and causes two GHR molecules to dimerize

Brings JAK2 molecules close together

JAK2 phosphorylates tyrosine residue on intracellular domain

Phosphorylated tyrosine form site for STAT proteins

STAT protein bind to phosphorylated tyrosine

JAK2 phosphorylates STAT5

Phosphorylated STAT5 dimerize

Dimerization allows STAT5 to move into nucleus

STAT 5 moves into nucleus

STAT5 binds to specific DNA sequences and triggers transcription of IGF-1 genes, metabolism, cell growth and proliferation

Acromegaly

Tumor during puberty

Dwarfism

Autoimmune

Acromegaly

Tumor after puberty

ADH is a

Peptide hormone

ADH is secreted by the

posterior pituitary

ADH

Promotes reabsorption of water back into circulation

ADH binds to receptors in

the distal and collecting tubules

Aquaporins transport

Solute free water back into the blood

The transport of solute free water back into the blood

decreases plasma osmolarity and increases urine osmolarity

Aquaporin 2

Mediates ADH activity

Aquaporin 3

Reabsorption of water into the blood

Binding of ADH stimulates

transcription of aquaporin 2 gene

Transcription of Aquaporin 2 causes

Aquaporin 2 to be inserted int the apical membrane

Aquaporin 3 is in

basolateral membrane

After water floods into cell through aquaporin 2 channels

It rapidly exits the cell through aquaporin 3

Hypothalamus senses osmolarity through

osmoreceptors

Osmoreceptors stimulate secretion from

neurons that produce ADH

loss of 15-20 % of blood volume results in

Massive secretion of ADH

ADH is stimulated by

decreases in blood pressure and volume

V1 class receptors

Mediate vascular smooth muscle contraction, increase intracellular calcium

V2 class receptors

Mediate renal action of ADH, increase cAMP

Hypothalamic (central) diabetes insipidus

Deficient ADH secretion, caused by head trauma, infections or tumors

Nephrogenic Diabetes Insipidus

Kidney doesn’t respond to ADH, caused by renal disease or mutation in ADH receptor gene or aquaporin 2 gene

Long term Stress Hormones

Cortisol

Short term Stress Hormone

Epinephrine

Epinephrine is secreted from

Inner medulla of adrenal gland