Table Of ContentVertebrate Endocrinology
Fifth Edition
David O. Norris, Ph.D.
Professor Emeritus,
Department of Integrative Physiology,
University of Colorado at Boulder,
Colorado, USA
James A. Carr, Ph.D.
Professor,
Faculty Director, Joint Admission Medical Program,
Department of Biological Sciences,
Texas Tech University,
Lubbock, Texas, USA
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Dedication of the
Fifth Edition
Wededicatethisvolumetothe many
Vertebrate Endocrinologists whose researchefforts
are represented here aswell as tothe manystudents ofendocrinology
thathave helped us refine our understandingofthis vast field andhow
to communicate it effectively.
Wewish tothankour editors,MeganWicklineand Mara Conner,
for their able assistance throughoutthisrevision aswell asthe marvelous
illustrators who broughtourideasinto colorfuland informativevisuals.
Additionally, we owe agreatdebt toour wives,Kay Norris and Deborah Carr,
for their patience and support during the preparation ofthis edition.
Preface to the
Fifth Edition
Fifty years ago, I read two new books that shaped my literature. For example, in one month there may be (1)
professionallife.ThefirstwasATextbookofComparative information about bioregulation in new species that influ-
Endocrinologyby AubreyGorbmanandHoward A.Bern ences our understanding of the evolution of endocrine
(1962) that contained virtually everything known about systems,(2)discoveryofnewbioregulatorychemicalsthat
invertebrate and vertebrate endocrinology at that time. contribute to coordination of activities within cells,
The second book was Silent Spring by Rachel Carson. between cells, and among organs and organ systems and
Thus began my development as an “environmental endo- even between organisms, (3) new understandings or treat-
crinologist”long beforetheterm appearedin print.Since mentsforaspecificclinicaldisorder,and(4)newevidence
that time there has been exponential growth in our ofdisruptionofendocrinefunctionsinhumansandwildlife
knowledgeanditwouldtakemanyvolumestoadequately by chemicals previously believedto besafe.
summarize it today. We thought the old lines drawn In an attempt to make the content of Vertebrate
between the disciplines of endocrinology, neurobiology, Endocrinologymorerepresentativeofthisvastandrapidly
and immunology were relatively clear 50 years ago but changingfield,Ihaveaddedaco-author,Dr.JamesA.Carr,
now they have become indistinct. All three fields employ Professor of Biological Sciences at Texas Tech University
chemical messengers affecting target cells through tohelpwiththistask.Additionally,theillustrations(mostly
specific receptors, often involving the same messengers infullcolor)havebeencompletelyredonetohelpstudents
and receptors, and we now recognize that the nervous, better conceptualize the major concepts. Rather than
endocrine, and immune systems each influence the activ- produce a compendium, we have attempted to provide
ities of the others. Thus, a broader, integrated concept of a current overview and interpretation of chemical
chemical bioregulation for physiology and behavior has bioregulation of vertebrates with a basic framework for
emerged that incorporates these three disciplines. helping students access and understand the primary bio-
Furthermore, a great variety of man-made chemicals regulation literature. Vertebrate Endocrinology is orga-
related to products we use every day are appearing in nized to challenge advanced undergraduates and graduate
aquatic and terrestrial environments at extremely low students interested not only in mammalian or human
concentrations.Thesesamechemicalsareassociatedwith endocrinology but those wishing to examine comparative
endocrine, immunological, and neural disorders in labo- vertebrate endocrinology aswell.
ratoryrodentsandverylikelyinhumans.Similarimpacts
are being described for aquatic and terrestrial wildlife. David O. Norris
Consequently, an understanding of endocrinology and ProfessorEmeritus,DepartmentofIntegrativePhysiology,
other chemical regulatory mechanisms and their interac- UniversityofColoradoatBoulder,Colorado,USA
tions is essential for our future on Earth.
James A. Carr
Vertebrate or comparative “endocrinology” (i.e., bio-
regulation)hasbecometoobroadafieldforanyoneperson Professor,FacultyDirector,JointAdmissionMedicalProgram,
to keep abreast of, with hundreds of new publications DepartmentofBiologicalSciences,TexasTechUniversity,
appearing each year in the clinical and non-clinical Lubbock,Texas,USA
xi
Chapter 1
An Overview of Chemical Bioregulation
in Vertebrates
Endocrinology as a scientific subdiscipline within physi- deals with chemical regulation of virtually all biological
ologybeganalittleover100yearsagoasthestudyofcertain phenomenainanimalsatthemolecular,cellular,organism,
glands called endocrine glands, or glands of “internal andpopulationlevelsoforganization.Thestudyofchemical
secretion”thatsecretedtheirproductsintotheblood.These regulation or bioregulation can be defined to include
secretions were called hormones (hormon, to stimulate or secretions of the endocrine system, nervous system, the
excite)becauseoftheireffectsondistanttargetcells.Each immune system, and virtually all cells in the body that use
hormonebindstoaspecificreceptormoleculelocatedinor chemical messengers to communicate with one another
on a target cell, and the resultant hormoneereceptor (Figure 1-1). The many secretions involved as internal
complex causes a measurable change in the target cell. chemicalmessengerscanbecalledbioregulators.
Many mechanisms employed in the vertebrate endocrine Learning about the intricacies of how the activities of
system have their counterparts among invertebrate animals animals are regulated and coordinated by bioregulators is
aswellasinmicrobialandbotanicalorganisms.Originally one of the most fascinating and complicated endeavors in
a traditional field of specialization that focused on the biology. Every act that an animal performs is initiated,
endocrine glands and their secretions, endocrinology has modulated,orblockedbybioregulators.Understandingthe
expanded as a specialty within physiology and now endocrine systems of invertebrates and vertebrate animals
Chemical Bioregulation
Targets Targets
Hormones Neurocrines
Nervous system
Endocrine system
(Neurotransmitters,
(Hormones,
Neuromodulators,
Cytocrines)
Neurohormones,
Cytocrines)
Immune system
(Hormones,
Cytocrines)
Hormones,
Cytocrines
Targets
FIGURE1-1 Chemicalbioregulation.Theendocrinesystem,nervoussystem,andimmunesystemeachsecretesitsownbioregulators:hormones,
neurocrines,andcytocrines,respectively.However,allofthesesystemsinfluenceeachother,andfromahomeostaticviewpointwecanassumethey
functionasonegreatbioregulatorysystem.
1
VertebrateEndocrinology.http://dx.doi.org/10.1016/B978-0-12-394815-1.00001-X
Copyright(cid:1)2013ElsevierInc.Allrightsreserved.
2 VertebrateEndocrinology
isessentialifweareevertounderstandhowbioregulatory I. THE COMPARATIVE VERTEBRATE
mechanismsandsystemsevolvedinanimalsandhowthey APPROACH
operatetomaintainthevastarrayoflivinganimalspecies.
Furthermore, the continued health of each ecosystem Comparative vertebrate endocrinology emphasizes the
depends on continued reproductive success of its compo- evolution of bioregulatory systems and the discrete struc-
nent animal species. tures and bioregulators that constitute the vertebrate
Because the nervous system and endocrine system act neuroendocrine and endocrine systems. Also of interest is
together to integrate environmental information with bio- theevolutionofvertebrateendocrineglandsandsecretions
regulationofphysiologyandbehavior,asubdisciplinecalled from invertebrates. Vertebrate endocrine systems may be
environmental endocrinology has emerged within the studied in a variety of ways. Some comparative endocri-
more traditional approaches to endocrinology. This area of nologistsmayhaveabasicinterestinfishesorreptilesand
researchnotonlyisfocusedonnaturalenvironmentalfactors study their endocrine systems to better understand their
such as pheromones, behavior, light (e.g., photoperiod), ecology and evolution. Others may be interested in
and temperature but has also expanded to include effects a specific phenomenon, such as aging, learning, or repro-
of pesticides, heavy metals, and all manner of organic duction,andemploynon-mammalianvertebrates asmodel
compounds added to the environment by human activities. systems in which to unravel basic mechanisms or evolu-
Thesechemicalscanalternormalbioregulatorymechanisms tionary relationships. Certain procedures may be more
bymimickingorinhibitingtheworkofnaturalbioregulators. readily performed on non-mammals, where processes are
This interference of endocrine bioregulation by environ- spreadoutstepwiseovertime,whereasinthemammalthese
mental pollutants and some natural chemicals is called steps all occur simultaneously. Comparative approaches
endocrine disruption, and these chemicals are called may have direct applications for aiding our understanding
endocrine-disrupting chemicals (EDCs) or endocrine- of these same phenomena in mammals including humans.
activechemicals(EACs). There are numerous examples of basic research in non-
The application of the estrogenic mimic diethylstil- mammalian vertebrates that have had direct applications
bestrol (DES) to cattle and to pregnant women was to human biology. For example, Spiedel made the first
recognizedmanyyearsagobyJohnMcLachlinandothers observation of neurosecretory neurons in the posterior
as causing a disruption of normal endocrine function that spinal cord of fishes. Later, Ernst and Berta Scharrer
has serious consequences for exposed animals and their extended this observation to the description of the
offspring. Recent evidence suggests permanent effects of hypothalamusepituitary neuroendocrine system. Geneti-
DES exposure that can be transmitted to subsequent callycontrolledplatyfishstrainshaveprovidedasystemfor
generations in both laboratory mice and humans. The use studying the bioregulation of aging and the reproductive
of the pesticide DDT and polychlorinated biphenyls system in relationship to genetic factors. Many species of
(PCBs) was banned in the United States when it was fishes are used extensively as models for stress, growth,
recognizedthattheywereaccumulatingintheenvironment carcinogenesis,aging,andbehavioralstudies.
andwereaffectingthehealthofbothwildlifeandhumans. Thetoadurinarybladderwasanexcellentinvitromodel
However,itisnowrecognizedthatthepotentiallyharmful for initial studies of the mechanism of action for the
nature of extremely low concentrations of estrogenic mineralocorticoid hormone aldosterone. Similarly, the
(feminizing and demasculinizing) pollutants in the envi- amphibian ovarian folliclehasprovidedaninvitrosystem
ronmentrepresentsagreaterthreatthaneverbefore.Louis forstudyingthebioregulationofoocytematurationandthe
P. Guillette, Jr., in Florida, was the first to observe that process of ovulation. Studies of non-mammals have been
a natural population of alligators exhibited abnormal crucial for understanding mechanisms of tissue induction
sexual development after exposure in nature to low andchemicalregulationofgeneactivityduringembryonic
concentrations of DDT and its metabolite DDE. Soon, development and differentiation. Numerous important
through the efforts of John Sumpter and numerous hypotheses about development were first tested in
colleaguesintheUnitedKingdomandEurope,evidenceof amphibians. The discovery by Alberto Houssay that
reproductivedisturbancessurfacedthatwerearesultofthe removal ofthepituitaryglandgreatlyreducedtheseverity
exposure of fishes to incredibly low concentrations of oftheremovalofthepancreasinatoadbecameamodelfor
estrogeniccompoundspresentinwastewatereffluents.We studying diabetes mellitus using dogs. The origin of the
have nowobserved similar effectsofwastewater effluents gonadotropin-releasing hormone (GnRH) in neural ecto-
in the United States, as well. Knowledge of the intricate dermandthesubsequentmigrationofGnRHneuronsfrom
workings of the endocrine system is essential for the olfactory placode to the hypothalamus were first
understandinghowsucheffectshappenandtocomprehend reported by Linda Muske and Frank Moore in an
the enormous implications of these observations (see amphibian. Additional confirmation of the origin of the
ahead). pituitary was performed using transplantation of normally
Chapter | 1 AnOverviewofChemicalBioregulation in Vertebrates 3
pigmented toad embryonic cells into albino toad embryos as illustrated in Figure 1-3. The first of these involves
andfollowing their pigmented descendents. the nervous system. Neurons produce neurocrine bio-
Furthermore, ingenious experiments using chickene regulators called neurotransmitters or neuromodulators
quail chimaeras with cytologically distinct cell markers thataresecretedintothesynapsesformedwheretheymake
verified the neural origin of a number of endocrine cells. direct connections with their target cells (typically other
ThelizardAnoliscarolinensiswasusedbyRichardJonesto neurons,musclecells,orglandcells).Onceaneurocrineis
studyhormonalandneuralcontrolofthealternatingpattern bound to its receptor molecule, it brings about distinct
ofovulationbythepairedovaries,aphenomenonthatalso changesinthepostsynapticcell.Theparallelismsbetween
occursinhumanswhereitismoredifficulttostudy.Avian endocrine cell and neuron, hormone and neurocrine, and
systems have been used extensively for studies of devel- target cell and postsynaptic cell are obvious. Only the
opment,neurobiology,immunology,cancer,andmolecular locationandchemicalcompositionofthemediumthrough
genetics.F.AnneMcNabbhasusedthequailasamodelfor which the bioregulator travels to reach its target cell
theactionsofacommonpollutant,ammoniumperchlorate, separate hormones from neurocrines.
onthe inhibition ofthyroidfunction. In the 1950s, Berta and Ernst Scharrer recognized that
Thediscovery ofpheromonesamonginvertebratesand some neural regulators were released into the blood like
later studies in non-mammalian vertebrates as well as in hormones. These neural hormones were named neurose-
miceandvoleshasledtonewunderstandingsintherolesof cretions or neurohormones to distinguish them from
such secretions controlling mammalian reproductive and neurotransmitters, neuromodulators, and the traditional
maternal behavior. Each of these systems has wide appli- hormones. It seems that it was easier to formulate more
cabilitytoothervertebratesaswellastothemechanismsof definitions than to acknowledge that certain brain regions
hormone actions. were also endocrine glands. Those neurons that secrete
neurohormones are sometimes called neurosecretory
II. THE ORIGINS OF BIOREGULATION neuronstodistinguishthemfromthe others. Althoughall
neurocrines are actually neurosecretions, that latter term
Regulatory chemicals were probably essential for the unaccountablyhasbeen reservedfor the neurohormones.
survival of the first living cells both for coordination of Later, the separation of neural and endocrine systems
internaleventsandforcell-to-cellinteractions(Figure1-2). became even more blurred for us when it was learned that
Secretions that favored survival of the secreting cell no some established hormones also are produced within the
doubt led to further evolution of new chemical bio- nervoussystem,wheretheyfunctionasneurotransmittersor
regulators. Thus, bioregulation probably had its origin in neuromodulators (see Table 1-1). It soon became common
local secretions that affected nearby cells as well as bio- knowledge that parts of the nervous system have control
regulators that affected internal cellular processes. The overcertainportionsoftheendocrinesystemthroughdirect
evolution of multicellular aggregates and eventually of innervation or via neurohormones. Likewise, hormones
multicellularorganismsallowedfurthercell-to-celltypesof wereseen toinfluencemarkedly notonly thedevelopment
bioregulation but more importantly also allowed for the ofneuralsystemsbutalsotheiractivity.Hence,ourconcept
eventual evolution of endocrine and neural bioregulation. of a neuroendocrine division within the endocrine system
The earliest appearance of neurons is noted in the most was established in physiology. Discovery of specific
primitive of multicellular animals, the cnidarian inverte- chemicals produced by diverse cellular types and released
brates (Cnidaria), and these neurons secrete both peptides into extracellular fluids including blood, lymph, cerebral
and non-peptides that function as typical neural and local spinalfluid,andinterstitialfluidhasbroadenedtheconcept
bioregulators.Theendocrineglandsthatsecretehormones ofchemicalbioregulationstillfurthertoincludecell-to-cell
did not appear until the type of internal transport mecha- chemicalcommunicationthatisnotmediatedviatransport
nisms we call blood vascular systems developed. These inthebloodoratasynapse.Additionalsourcesofhormones
bioregulatory systems have been termed neuroendocrine were discovered to come from traditionally non-endocrine
systems because they involve both neural and endocrine tissuesororganssuchastheheart,theliver,adiposetissue,
components. Complex neuroendocrine systems have and skeletal muscle. The organization of the vertebrate
evolved in annelids (Annelida), mollusks (Mollusca), endocrinesystemisoutlinedinFigure1-4.
insects,arachnids,andcrustaceans(Arthropoda),aswellas Chemical bioregulators were also discovered that are
inthe chordates(including thevertebrates). used for cell-to-cell communication within tissues. Such
bioregulatorsthataresecretedintoextracellularfluidrather
III. CATEGORIES OF BIOREGULATORS than the bloodstream are named “local hormones” or
cytocrines. This category includes locally acting growth
In addition to traditional endocrine regulation, we now factors, mitogenic regulators, embryonic tissue-inducing
recognizeseveralotherpatternsofchemicalbioregulation, substances, secretogogues (secretion-enhancing factors),
4 VertebrateEndocrinology
(A)
(B)
Cells accumulate toxins, nutrients, etc.
Toxins
Nutrients
Receptors
Bioregulators
FIGURE1-2 Originsofchemicalcommunication.(A)Earlycellslivingintheprimordialseasdeveloped“receptors”(hereshownonlyonthecell
membrane)forrecognitionofwater-solubletoxins(bluecircles)andnutrients(redsquares)aswellasinternal“receptors”(notshown)forlipidsthatcould
readilypassthroughthemembrane.Someofthese“receptors”transferredthesemoleculesintothecellformetabolismordetoxification.(B)Inadditionto
accumulatingmoleculesintracellularly,earlycellsalsoreleasedspecialmoleculesintotheenvironmentthatweredetectedviareceptorsonothercellsand
servedasamechanismforcell-to-cellcommunication.Variousfeaturesoftheseancientmechanismsforaccumulation,detoxification,metabolism,and
chemicalcommunicationhavepersistedinoneformoranotherinalllivingcellstothisday.
inhibitors,andimmuneregulators.Ifcytocrinesalsoaffect Chemicalsreleasedfromneuronsintothecerebrospinal
the emitting cell, they are sometimes termed autocrines. fluid(CSF)donotquitefitthedefinitionofneurohormone,
When they affect other cell types, they are called para- as they are released into a filtrate of blood, but they do
crines. However, both types of local cytocrine secretion not quite fit the definition of paracrine secretion, either.
into the general extracellular fluids are sometimes loosely For our purposes, we will refer to these bioregulators as
referred toas paracrine secretion. neurohormones.
Chapter | 1 AnOverviewofChemicalBioregulation in Vertebrates 5
Ordinary FIGURE 1-3 Bioregulator organization.
neurons Chemical communication involves neurocrines,
including neurotransmitters or neuromodulators
(1) and neurohormones (2), as well as hormones
(3)andautocrine/paracrineregulators(4).Theliver
1 andkidneyserveasmajorsitesforthemetabolism
1 andexcretionofbioregulators.
Neurosecretory
(ns) neuron
Autocrine
Neurosecretory 2
(ns) neuron
4
1
Endocrine Paracrine
2 cell
3
Liver Kidney Target
cell cell cell
Metabolism Excretion Effect
Intracellular chemical messengers that govern intra- subclasses of semiochemicals have been identified on
cellular events have been called intracrines. These intra- functionalbases.Pheromonesaresemiochemicalsthatact
crine bioregulators would include chemicals such as the only on other members of the same species. Primer
second messengers and transcription factors that are dis- pheromones usually initiate a series of physiological
cussed inChapter3. events such as gonadal maturation. Signal or releaser
In its broadest sense, the study of bioregulation may pheromones trigger immediate behavioral responses such
include specific chemical messengers released by one as sexual attraction or copulation. Allelomones are inter-
organism into its environment that may affect the physi- specificsemiochemicalsandarefurtherseparatedintotwo
ology or behavior of other individuals of that species or types. If only the emitter of the semiochemical benefits
evenofanotherspecies.Agoodnameforthesesubstances fromtheeffectontheotherspecies,theallelomoneiscalled
might have been “exocrines,” but that term had already an allomone. The well-known odor released by skunks is
been assigned to the products of exocrine glands adramaticexampleofanallomonethatprotectstheskunk
(e.g., salivary glands,sweat glands, mammaryglands,and from would-be predators. When only the recipient species
portions of the liver and pancreas) that secrete their prod- benefits,theallelomonemaybetermedakairomone.The
ucts into ducts through which the secretions are conveyed release of the simple metabolite l-lactate in the sweat of
totheirsitesofactiononthefreesurfaceoftheepithelium humansattractsfemalemosquitoes,whichobtaintheblood
in such places as the digestive tract or the skin. These meal necessary for their reproduction. l-Lactate, then,
externally secreted bioregulators are called “ecto- couldbeclassified asakairomone,forthereisnoobvious
hormones” or semiochemicals (semio, signal). Three benefit tothe emitterand infact it may harm the emitter.
6 VertebrateEndocrinology
In summary, intraorganismal bioregulation can be A bioregulator has a distinct life history analogous
classified as endocrine (hormones), neurocrine (neuro- to that of an organism, as illustrated in Figure 1-5 for
transmitters,neuromodulators,neurohormones),paracrine atypicalhormone.Abioregulatorisborn(synthesis),may
(cytocrines, autocrines), or intracrine (intracellular regu- exist first as an immature stage (inactive precursor mole-
latory messengers). Semiochemicals (pheromones and cule) that later is transformed to a mature form (metabo-
allelomones) are specialized for interorganismal commu- lized to an active molecule), has a life (binds to receptors
nication.Alistingofthesetypesofbioregulatorsandtheir and produces an effect), and dies (is metabolized and/or
definitions are provided in Table 1-2. excreted).It only lacksthe abilitytoreproduce itself.
Mostbioregulatorsarepeptides,proteins,orderivatives
of amino acids. Some are lipids (e.g., steroids) and still
others are nucleotides or nucleotide derivatives. A discus- IV. GENERAL ORGANIZATION OF
sion of the chemical nature of regulators, how they are BIOREGULATORY SYSTEMS
synthesized,howtheyproducetheireffectsontargets,and
how they are metabolized is the subject of Chapter 3. As stated above, the endocrine system and the nervous
However, before examining these bioregulators more systemarethesourcesformostofthechemicalmessengers
closely, we must consider some more general features of we have defined as bioregulators. Traditionally, the verte-
bioregulatory systems. brate neuroendocrine system includes the brain and the
pituitary gland plus the classical endocrine glands they
control:thethyroidgland,thepairedadrenalglandsand
gonads(testesandovaries),andtheliver.Inaddition,there
areindependent endocrine bioregulatorsdthatis,those
TABLE1-1 SomeMammalianNeurocrineBioregulators* not directly under the influence of the brain and/or pitui-
tary. This would include the adipose tissue, parathyroid
ClassofRegulator Example
glands, thymus, heart, endocrine pancreas, organs of
Nonpeptides Acetylcholine(ACh) thegastrointestinaltract,pinealgland,andkidney.The
Carbonmonoxide(CO) major focus of this textbook is on the neuroendocrine
Dopamine(DA)
systemsofmammalsandnon-mammalianvertebrates.The
Epinephrine(E)
independent endocrine glands are discussed for some
g-Aminobutyricacid(GABA)
Glutamate special cases (for example, regulation of calcium homeo-
Nitricoxide(NO) stasis, which is discussed in Chapter 14) and when they
Norepinephrine(NE) interact with the bioregulators of the neuroendocrine
Serotonin(5-HT)
system such as in the bioregulation of metabolism
Hypothalamic-releasing Corticotropin-releasinghormone (Chapters 12 and 13).
neuropeptides (CRH) The vertebrate neuroendocrine bioregulatory system
Gonadotropin-releasinghormone
(Figure1-4)involvesamajorportionofthebraincalledthe
(GnRH)
hypothalamus, that portion of the brain located directly
Prolactin-releasinghormone(PRH)
Somatostatin(SSorGHRIH) above and anterior to the pituitary gland. The detailed
Thyrotropin-releasinghormone(TRH) organization and operation of this system are described in
Chapters4and5.Specialgroupsofneurosecretoryneurons
Otherneuropeptides AngiotensinII(Ang-II)
Argininevasopressin(AVP) in the hypothalamus produce a variety of neurohormones.
Atrialnatriureticpeptide(ANP) Some of these neurohormones (i.e., releasing and release-
Brainnatiureticpeptide(BNP) inhibiting hormones) control the secretion by the pituitary
Cholecystokinin(CCK)
g gland of peptide and protein hormones called tropic
Ghrelin
hormones (tropic is derived from the Greek word trophe,
Insulin
Kisspeptin(Kp) referring to nutrition). These tropic hormones regulate the
Leptin endocrine activities of the thyroid gland (secretes thyroid
NeuropeptideY(NPY) hormones; see Chapters 6 and 7), the adrenal cortex
NeuropeptideYY(PYY)
(secretes corticosteroids; Chapters 8 and 9), the gonads
peptidehistidineisoleucine(PHI)
(secretereproductivesteroids;Chapters10and11)andthe
SubstanceP(SP)
Vasoactiveintestinalpeptide(VIP) liver (secretes an essential factor for growth; Chapter 4).
Furthermore,sometropichormonesinfluencemoregeneral
*Someofthesemoleculesmayfunctiononlyasaneurotransmitter,neu-
aspectsofgrowth,metabolism,andreproductionandaffect
romodulator, neurohormone, or paracrine regulator whereas others may
performmultipleroles. many non-endocrine target tissues. Additional neurohor-
mones(vasopressinandoxytocin)arestoredinpartofthe
