Chemical Regulation

Glands and Hormones

 Cellular Secretions
■ All cells secrete a surface coat
■ Epithelial cells often secrete a mucous layer -
giving rise to the term mucosal layer for the outer
epithelium
■ Secretions often function for protection and in
cellular recognition
■ Many cells also secrete signaling substances
Some Cellular Secretions
 Classification of Signaling Cells
■ Autocrine - affect activities of the cell itself
– Autoinhibition within the autonomic nervous system
■ Paracrine - affect the activities of neighboring
cells
– Inflamatory response is a good example
■ Endocrine - released into blood stream for action
upon distant targets
■ Exocrine - released onto the surface of the body,
both outside and internally such as within the
digestive system
Autocrine and Paracrine
Two Types of Endorcine Action
Classic Endocrine Action
Endocrine Mechanisms
 Diversity of Action
■ Some secretions can show multiple actions
– Calcitonin - produced in gills of pacific salmon
and in utimobranchial gland as well
■ Modifies calcium uptake within in the gills
themselves (autocrine and paracrine)
■ Ultimobranchial secretion is an endocrine
secretion
 Pheromones
■ These are exocrine chemicals intended to initiate a
response in another individual of the same species
or another species in some cases
– Sex attractants or
stimulants
– Antipredator
chemicals
– Chemicals used to
coordinate activity
of animals within
a group
 Pheromones
(A type of exocrine activity)
Example of Insect Pheromone
Behavioral Pheromonal Effects
Honey Bee Activity Under Pheromonal Control
■ 1. Activation of Guard Bees
■ 2. Attraction of Colony Bees
■ 3. Movement/Buzzing of Caged Bees
■ 4. Stinging of Still Objects
■ 5. Stinging of Moving Objects
■ 6. Bees Flying in Air
■ 7. Sound Production
■ 8. Inhibition of Nasonov Scenting (used to attract
other workers to water source, swarming location or
nest entrance)
■ 9. Inhibition of Nasonov Attraction
■ 10. Abdominal Contractions
Potential Pheromone Release Sites

Whitetails have four sets of external

glands that are used primarily for
communication. Gland secretions can
describe a deer's social status, breeding
condition and health.

Alarm 
Pheromones
Pheromone Humor
 Other Exocrine Functions
■ Mucous secreted by snails aids in movement
■ Aids in digestion and swallowing
– Saliva- lubricates food for swallowing
– Saliva - also contains digestive enzymes
– Pancreatic and other digestive secretions -
lubricate and contain digestive enzymes
 Surface Secretions
■ All animal cells secrete a cellular coat or
glcocalyx
– Chemical composition allows certain cells to
recognize and adhere to one another
– Forms the basis of immune recognition
– Fundamental in organ formation
■ Mucus secreted by some cells is often used as a
surface protectant
■ Collagen - give tissues form and rigidity and
create surfaces along which cells can slide
 Packaging and Transport
■ The processes of synthesis and packaging occur in
one part of the cell
■ Secretion takes place in another cellular region
■ Most substances packaged within secretory
vesicles or granules
■ Some substances may be released directly as free
molecules (steroids which are lipid soluble)
 Formation and Delivery of Vesicles
Proteins are synthesized on the endoplasmic
reticulum and accumulate within the lumen
Vesicles bud off after the material passes to the
smooth ER
These newly formed vesicles migrate to the Golgi
complex where they fuse with the Golgi cisternae
Processing and modification occurs within the Golgi
New vesicles break off of the Golgi and fuse to form
secretory vesicles
Synthesis and Packaging of Proteins
Micrograph of Process
Golgi Structure
 Sorting of Vesicles

Sorting is carried
out by the Trans
Golgi Network

If deliverd initially
to the basolateral
membrane and then
to the apical mem-
brane process is
called tanscytotic
delivery
 Storage of Secretory Products
■ Large proteins retained simply based upon size
■ Small hormones bound to larger accessory
molecules, often proteins
■ Continual uptake from the cytosol - can be
blocked
■ Some hormones such as steroids are released
quickly upon production
■ Thyroid hormones can be stored in extracellular
spaces termed follicles for up to several months
 Activation of Secretion
■ Stimulation of cell induces release
■ May be hormonal or nervous induced
■ Direct stimulation occurs in some cases - increase
in plasma osmolarity for example
■ Electrical stimulation
Role of Calcium in Endocrine
Activation
 Control of Glandular Activation
■ Some secretions come from combined activity of
many cells in a gland
■ Some glands show a resting level of secretion that
can be either modulated up or down
■ Other glands respond only to a homeostatic
change
■ Signals
– Neurotransmitters
– Direct homeostatic change (osmolarity)
– Can be influenced by both conditioned and
unconditioned reflexes
 Mechanisms of Secretory Action
■ Apocrine secretion - apical portion of cell breaks
off and cell then reseals itself (molluscan exocrine
and some human sweat glands)
■ Merocrine secretion - apical portion pinches off
and releases product into lumen of the gland
(digestive glands of mammals and many arthropod
and annelid exocrine glands)
■ Holocrine secretion - entire cell is cast off (insect
and moluscan exocrine and mammalian sebaceous
glands)
Secretory Mechanisms
 Glandular Structure
■ Glands are classified as either endocrine (ductless)
or exocrine (ducted)
■ Endocrine glands secrete hormones
■ Exocrine glands secrete fluids through a duct
■ No such thing as a typical gland
– Endocrine glands are diverse in structure and
function and show no distinctive features other
than vascularization
– Exocrine glands do often have specific duct
arrangements
Exocrine Gland Forms
 Endocrine Glands
■ First endocrinology
based on work with
young roosters and
the development of
their combs
(1849-Berthold)
 Origin of Term Hormone
■ Derived from Geek of “I Arouse” - introduced by
Starling in 1905
■ Starling described three characteristics of
hormones
– Are synthesized by specific tissues or glands
– Are secreted into the bloodstream which carries
them to the site of action
– Change the activities of the target tissues or
organs
 Criteria for Endocrine Function
■ Ablation produces deficiency symptons
– May be difficult in tissue is part of a structure with
another function (atrial)
■ Replacement of ablated tissue elsewhere in the
body should remove the deficiency symptoms
– May be difficult due to severing of nervous system
connections
■ Injection of suspected hormone will relieve
deficiency symptoms
– Basis of replacement therapy
 Further Support Evidence
■ Chemical analysis and synthesis of hormone
■ Testing of synthesized version for similar function
■ Identification of storage sites for hormone is
suspected tissue
■ Demonstration of actual release of hormone
 Chemical Classes of Hormones
■ Amines - include catecholamines epinephrine and
norepinephrine as well as thyroid hormones and
small amino acid derived hormones
■ Eicosenoids (prostaglandins, leukotrienes, and
other products of arachidonic acid metabolism)
■ Steroids - derived from cholesterol and include
testosterone and estrogen
■ Peptides and Proteins - largest and most complex
group
 Relationship of Endocrine and
Nervous System
■ Closely associated
■ Nervous system leads to rapid short term
responses
■ Endocrine system leads to slower often more
prolonged responses
■ In some respects the nervous system is the most
important endocrine organ
– Produces several hormones which regulate the
activity of other endocrine organs
– Neurohormones often keep hormonal release
modulated up or down from a basal level
 Feedback Control
■ May be either feedforward or feedback regulation
■ In feedforward the secretion is not modulated by
the consequences of the secreted hormone
■ Most feedback systems are negative
■ There may be either long loop or short loop
feedback
■ In short loop the hormone itself or its direct effect
alters production
■ In long loop there are more elements included
Long vs Short Loop Feedback

No feedback

In a positive feedback
situation ­ some process 
will ultimately couter 
the process and reverse
the increase.
 Neuroendocrine Systems
■ Neurohormones are produced by specialized neurons
called neurosecretory cells
■ Secretory vesicles are often larger
■ Secretory transport is accelerated
■ Release hormones into a neurohemal organ where
hormones are taken up by capillaries
■ Neurosecretory cells of the hypothalamus control the
activity of two distinct pituitary regions
– Those secreted within the hypothalamus regulate
anterior pituitary
– Those secreted within the pituitary regulate posterior
pituitary
Hypothalamus-Pituitary
Relationship
 Important Tables In Text

Table 9.2 ­ Hypothalamic neurohormones

Table 9.3 ­ Tropic hormones of anterior pituitary
Anterior 
Pituitary
Control
(acidophils) All basophils
(basophils)

(acidophils)
Posterior 
Pituitary
Control
Cellular Mechanisms of Hormonal Action
■ Hormones exert their action by acting on receptors
in one of two locations
– Lipid-soluble hormones (steroid and thyroid)
bind to cytoplasmic receptors and are
transported to nucleus. - lead to long term
changes lasting hours to days
– Lipid-insoluble hormones bind to cell surface
receptors which often leads to the production of
one or more second messengers - lead to rapid,
short lived responses
Lipid-soluble Mechanism
Lipid Insoluble Mechanism
 Lipid Soluble Mechanisms
■ Hormones are carried in blood stream complexed
with a carrier molecule
■ Once dissociated they readily enter cells by way
of diffusion
■ They then bind with specific receptors in the
cytoplasm or nucleus
■ The hormone-receptor complex activates (in some
cases inhibits) transcription of specific genes
■ Some lipid soluble (aldosterone and estrogen) also
bind to surface receptors
 Lipid-insoluble Mechanisms
■ Binding to receptors on cell surface triggers the
production of a second messenger
■ There are three classes of second messengers
– Cyclic nucleotide monophosphates
■ cAMP and cGMP
– Inositol phospholipids
■ IP3 and DAG
– Ca2+ ions
Cyclic Nucleotides
Inositol Phospholipds and Calcium
Cyclic Nucleotide Signaling
 Amplification

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C­AMP
Production
C-AMP mediated action

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 Calcium Signaling Systems
■ Calcium has been identified as an important
signaling molecule
■ Two important cellular characteristics allow this to
take place
– The ability of cells to increase or decrease
cellular calcium concentrations over a wide
range
– The presence within cells of many proteins
whose activity is modulated by calcium
 Regulation of Cytosolic Calcium
■ Concentration in cytoplasm can be increased in
two ways
– By release of calcium from intracellular stores
■ Endoplasmic reticulum
– By influx of calcium from the cell exterior
through calcium channels
■ May be by activation of calcium channels through
another hormone regulated mechanism, electrical
activity, phosphorylation of a calcium channel or
receptor activation itself
 Calcium Binding Proteins
■ Many calcium binding regulatory proteins exist
■ Binding of calcium to the proteins leads to a
conformational shape change
■ One particularly important one is calmodulin
which mediates most intracellular calcium
regulated processes
■ Has receptor sites for four calcium - when
complexed it can bind to and activate many
enzymes and effector proteins
Calmodulin

CALcium MODULated proteIN.

Calmodulin Regulatory Activity
Second Messenger Role of Calcium

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Calmodulin Activation of Adenyl
Cyclase
 Second Messenger Networks
■ A single hormone may trigger several second
messenger systems by activating different types of
receptors
■ α adrenoreceptors and β adrenoreceptors are one
example of such a system
■ These pathways may be either convergent, leading
to the same general response or divergent leading
to differing responses
Divergent Pathway
Convergent Pathway
Serotonin Receptors
The figure depicts a system where the signal causes a G-protein to become active,stimulating the
membrane enzyme phospholipase C. This enzyme degrades cell membrane phosphatidyl inositol
releasing IP3 (inositol triphosphate) and leaving diacyl glycerol (glycerol with two fatty acids,
DAG). Both are second messengers, with IP3 causing the endoplasmic reticulum to release Ca++
(also a second messenger). The DAG activates protein kinase C, a kinase that is dependent on Ca++
for activity. Note that both second messengers play a role in the activation of protein kinase C. The
response made by the cell will depend on what targets for protein kinase C are available
 Physiological Effects of Hormones
■ Hormones fall into several categories with respect
to the type of responses they regulate
– Metabolic and Developmental
■ Glucagon, glucocorticoids, growth hormone,
insulin, norepinephrine and thyroxine
– Regulation of water and electrolyte balance
■ ADH, atrial natriuretic peptide, calcitonin, mineral-
corticoids, parathyroid hormone
– Reproductive hormones
■ Estrogens, progesterone, testosterone, oxytocin and
prolactin (first three are primary sex hormones)
 Alternative Classification
■ Kinetic - activate muscles, pigmentation changes,
secretory processes
■ Metabolic -influence cellular respiration rates,
regulate carbohydrate and protein balance, influence
electrolyte and water balance, regulate minerals such
as calcium and phosphorus
■ Morphogenetic - growth, molting, metamorphosis,
regeneration, gonadal maturation and function,
differentiation of genital ducts and development of
sexual characteristics
■ Behavioral - tropic effects on developing nervous
system, release of behavior patterns, sensitization to
specific stimuli which influence behavior
 Properties of Mammalian Hormones

Property             Steroids          Thyroxine       Peptides     Catecholamines

Feedback             yes                   yes                     yes                yes
regulation
of synthesis

Storage of       minimal      weeks            one day       several days
preformed                                                                    in adrenal
hormone               medulla     
Metablolic and Developmental

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Glucocorticoids and Glucagon

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Metabolic and Developmental

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Catecholamine Secretion
Catecholamine Effects
Growth Hormone and Thyroxine
Water and Electrolyte Balance

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Calcium Regulation
Reproductive Hormones

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Mammalian Sex Hormones
Primate Menstrual Cycle
 Prostaglandins
■ Long chain, unsaturated, hydroxy fatty acids
■ First discovered in the 1930's in seminal fluid
■ Thought to be produced by prostate gland
■ Very diverse with numerous functions
■ Use surface receptors even though they are lipid
soluble
■ Linked to cAMP second messengers
Prostaglandin Functions
 Invertebrate Hormones
■ Neurosecretory and other hormone producing cells
have been found in all invertebrates
■ Most of what is known is based on studies of
insect hormones
■ Insects show two basic life history patterns
– Hemimetabolous - egg, nymphal instars and
adult
– Holometabolous - egg, larval instars, pupa and
adult (adult bears no resemblance to larval
stagesa0
 Study of Insect Hormones
■ Studies first carried out between 1917 and 1922
■ Studies involved ligatures separating body regions
■ Concluded that pupation is based on production of
a circulating substance produced in the anterior
portion of the body
■ Work eventually determined that this substance
was a neurohormone secreted by the brain which
stimulate the prothoracic gland to produce molt-
inducing hormones
■ Parabiotic exeriments also facilitate such studies
Insect Study Methods

Application of JH induces larval 
cuticle
 formation in adult
 Major Insect Hormones
■ Parathoraciotropic (PTTH) - neurohormone
■ Juvenile hormone - produced by corpus allata
which is somewhat analogous to the anterior
pituitary (non-neuronal)
■ Ecdysone - produce by prothoracic gland - similar
to vertebrate steroids (non-neuronal)
■ Eclosion - neuropeptide from corpora cardiaca
■ Bursion - neurohormone of brain and nerve cord
 Insect Hormones

(NS)
(ES) (NS)

(NS)
(ES)
Insect Hormone Functions
Juvenile Hormone Levels
Juvenile Hormone:Ecdysone Interactions