METABOLISM I: INTERMEDIARY METABOLISM



ENDOCRINE INTENSIVE

AN ILLUSTRATIVE EXAMPLE: EPINEPHRINE

BIG ISSUES IN ENDOCRINE REGULATION

Getting the signal inside: How does a blood-borne hormone exert intracellular effects?

Balance of activation and inactivation: How do we keep signals from getting out of control?

Hormones are made and circulated in very small concentrations:

How are these signals amplified?

How can we measure them?

Specificity

What determines which cell types a hormone will interact with?

What adaptive purpose do multiple function hormones serve?

How and why might it make sense for multiple hormones to have the same effect?

COMPONENTS OF A SIGNALING SYSTEM: signaling cell, signal molecule, ligand, receptor, target cell

ARRANGEMENTS OF SIGNAL AND TARGET CELLS:

Autocrine, paracrine, neural, neuroendocrine, endocrine, allocrine (see chart)

CLASSIFICATION OF HORMONES BY MOLECULAR STRUCTURE

Hydrophilic: proteins, peptides, and their derivatives

Hydrophobic: steroids, thyroid hormones, eicosanoids

Gases: NO

LIFE CYCLE OF A HORMONE: why measuring the concentration of a hormone in the blood can’t always tell us how much hormone action there will be

Production

Transit between signaling cell and target cell

Action on cell

Disposal

HYDROPHILIC SIGNALING MOLECULES: proteins, peptides, aa derivatives

Molecule type

Production

Inactive precursors

Vesicular storage

In transit

What determines blood concentration of a hormone?

Special circulatory pathways: portal systems

Breakdown

Target cell

Intracellular transduction pathways

e.g., cAMP-mediated pathway

e.g., inositol phosphate mediated pathway

Receptors:

Three types: ion-channel linked, G-protein linked, enzyme linked

Number and affinity

Breakdown

SAMPLE INTRACELLULAR TRANSDUCTION PATHWAY

Overview of cAMP-mediated transduction pathway

What is the overall goal of this pathway?

Work on collaborative exercise

Discuss answers and fill in details

Threshold effects

Old dogma: hydrophilic hormones cause proteins to be phosphorylated

New truth: hydrophilic hormones can cause protein synthesis, too

CRE = cAMP response element (regulatory DNA sequence)

CREB = CRE binding (protein)

CBP = CREB binding protein

Turning the pathway off

Molecular toolboxes

Amplification steps

Specificity

Specificity collaborative/homework exercise

HYDROPHOBIC SIGNALING MOLECULES: steroids, thyroid hormones, Vitamin D

Production of steroids

Cholesterol derived

Similarity in structure

Transit

Binding proteins and their functions

Solubility

Stability

Preventing overdilution

Delivery to target cells

Law of mass action

Specific binding sites

Bound vs free hormone

Target cell actions

Degradation

THE HYPOTHALAMIC-PITUITARY AXES

Structure of pituitary gland (hypophysis)

Developmental origin

Posterior pituitary (neurohypophysis, pars nervosa)

Anterior pituitary (adenohypophysis; pars distalis, pars tuberalis, pars intermedia)

Endocrine pathways involving the hypothalamus and pituitary

Generalized pathway

Trophic hormones

Feedback loops involving the hypothalamus and pituitary

Short-loop feedback

Long-loop feedback

Stressor ( adrenal medulla releases epinephrine (ng/ml or pg/ml) (

Within seconds to minutes

Hepatocytes -- huge amounts of glucose released

Cardiac muscle cells -- increased heart rate

Arterial smooth muscle cells -- vasoconstriction

Increases blood pressure

Reduces heat loss

Gastrointestinal sphincter contraction

Pupil dilation – contraction of smooth muscle

Pancreas -- insulin secretion decreased

Brown fat cells -- stimulates thermogenesis (induces transcription of UCP1)

Kidney cells -- increase sodium reabsorption

Salivary gland -- inhibits fluid secretion

Epinephrine levels decrease rapidly after removal of stress

If stress continues, responses subside even when epinephrine levels are high

ARRANGEMENTS OF SIGNALING AND TARGET CELLS

|Signal cell |Signal released |Target cell type |Signal called |Signaling type |

|type |into | | | |

|any cell |extracellular fluid |same cell |Hormone |autocrine |

| |(ECF) | |Ex: | |

|any cell |ECF |neighboring cell |Hormone |paracrine |

| | | |Ex: | |

|Presynaptic neuron |synaptic cleft |Postsynaptic neuron or |Neurotransmitter |synaptic/neural |

| | |other excitable cell |Ex: | |

| | |(e.g., muscle) | | |

|neuron |blood |distant cell |Neuro-hormone |neuroendocrine |

| | | |Ex: | |

|Cell in gland |blood |distant cell |Hormone |endocrine |

| | | |Ex: | |

|Cell in gland |environment |Olfactory receptor cell in|Pheromone |allocrine |

| | |another individual |Ex: | |

|Cell in gland |Environment/ |Cell in another individual|Allomone |allocrine |

| |another individual | |Ex: | |

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Norris DO. 2007. Vertebrate Endocrinology, 4th ed. Boston: Elsevier.

PROHORMONE

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