Introduction to Organismal Biology (BIOL221) - Dr. S.G. Saupe; Biology Department, College of St. Benedict/St. John's University, Collegeville, MN 56321; ssaupe@csbsju.edu; http://www.employees.csbsju.edu/ssaupe/

Chemical Signaling:  A Primer

I.  Overview

A.  General:  Recall that cells/organisms require the ability to relay internal messages from one cell or part of the individual to another.  Communication can occur via:

electrical signals/messages - quick; transient; mostly animals
chemical signals/messages - slow; longer-lasting; animals & plants

The function of these messages is to:

1. coordinate growth & development activities
2. maintain homeostasis
3. respond to the environment

B.  Response System/cascade
    The generalized system by which animals and plants respond to signals/messages can be diagrammed as follows:
                  signal →  target tissue/cell →  receptor →  signal amplification (transducing mechanism)  →  response

1. Signals - may be external (alerting about environmental conditions) or internal (alerting body to internal conditions); signals are a form of energy - may be chemical, light, heat/cold, touch, sound, etc.
2. Receptor - must be designed for signal.  The receptor for light is a pigment; the receptor for a chemical is typically a protein (often embedded in membrane)
3. Transducing mechanism - refers to the complex response system by which activating the receptor initiates the response.

II.  Internal Chemical Signals (= hormones)
    Hormones are defined as: organic compound, active in low concentration, that is produced in one part of the cell/organism and has it action in another.  Thus, there is a separation of the site of production and synthesis.  The degree of separation varies:  in plants, usually little separation; in animals - in some cases there is little (autocrine), minimal (paracrine) or lots (endocrine).

    In animals - exocrine glands secrete hormones into the blood stream (e.g., hypothalamus, pituitary, kidneys, pancrease, ovaries, testis); endocrine glands secrete hormones in ducts other than circulatory system (pancreas, salivary glands)

III.  Evidence for the existence of hormones

A.  Plants  - check out the Case Studies in phototropism and fruit set in soybeans
B.  Animals - check out the secretin example in dogs (Case Study)

IV.  Criteria to establish that a chemical is a hormone (check out the Case Study)
    Essentially, four criteria need to be met:

1. exogenous application causes the response
2. lowering endogenous levels prevents the response
3. lowering endogenous and then adding the chemical exogenously returns the response
4. endogenous levels should increase before the response is detected

V.  Chemistry of Hormones
    A variety of molecules are used as hormones.  These include:

• polypeptides (=proteins)
• steroids
• terpenoids - built from isoprene
• others - amino acids, etc.

VI.  Mechanism of Action

A.  General
    Hormones typically bind to receptors to initiate a response.  The receptors are usually proteins and can be located in the cell membrane (for hydrophilic, water-soluble hormones) or somewhere in the interior of the cell (lipid-soluble hormones like steroids).  The receptor then initiates a series of responses that amplifies the hormonal signal ultimately resulting in an increase in transcription and/or translation and/or protein activation.  The amplification process often involves protein kinases that add/remove a phosphate from an enzyme to activate/inactivate the enzyme (enzyme-inactive + Pi →  enzyme-active).  A general scheme includes:

hormone →  receptor →  amplification via protein kinases, G proteins, other →  transcription, translation, enzyme activation, other →  response

B.  Example 1 - Estradiol
    Estradiol is a steroidal sex hormone and readily crosses membranes.  Estradiol enters the nucleus and binds to a protein receptor (we know it is a protein because when a cell extract is treated with proteases there is no response) the activated protein/hormone complex binds to DNA at the promoter region activating transcription and ultimately translation.  Proteins that bind to DNA typically have regions called zinc-fingers.

C.  Example 2
    The water-soluble hormones, like noradrenaline, typically bind to a protein receptor embedded in the membrane (transmembrane protein).  The membrane protein then activates a cascade/amplification of events that can either:

• in the case of noradrenaline:  binds to receptor →  stimulates a G protein →  activates adenyly cyclase →  converts ATP to cAMP →  activates a cAMP-dependent protein kinase →  activates phosphorylase kinase →  activates phosphorylase →  hydrolyzes glycogen to glucose
   
• in other cases, hormones activate other cascade systems involving calcium ions and other secondary signalling molecules