Endocrinology
(Chapter 11)
Comp. Physiol.
Last revision: 10/15/98
Overhead: text (classic view of neural and endocrine regulatory systems)
Nervous and classical endocrine systems were for the longest time considered
quite distinct entities.
Nervous system: rapid transient responses – Endocrine system: slow long-lasting
effects.
Nervous system: Very short distance between effector cell and target cell –
Endocrine system: Long distance between endocrine cell and target cell
We know now that this classical division does not fit with reality. There is really a
continuum in the transition between nervous and endocrine systems, both in
respect to the distance between effector and target and also regarding the duration
of the response. The discovery of paracrine signaling certainly killed the idea that
only neurotransmitters act over short distances.
Electric synaps - Chemical synaps - Varicosities - Neuroendocrine systems Classical endocrine glands
Regulation of the activity of the gastrointestinal system in vertebrates is an
example where it is really difficult to distiguish between nerve and hormone
signaling. Several of the chemical signaling substances in the gut (e.g. CCK,
substance P, VIP) are used both as hormones and as neurotransmitters.
Overhead: Withers 11-2 (integration between neural and endocrine systems)
Nervs and endocrine cells often work intimately together in the regulation of
physiological systems. A typical neural reflex arc is rather similar to a 1st order
neur-endocrine loop. In both cases the signaling substance is made by neurons that
are located in the CNS. The practical difference is that the neurohormone is
carried some distance in the extracellular fluid. There are 2nd and 3rd order
neuroendocrine loops in which one or two of the links in the chain are made up by
either neurons or endocrine glands. There are indeed several systems that are build
upon a direct endocrine loop, in which the endocrine cells themselves sense the
stimulus and react accordingly.
All these control loops occur commonly in vertebrates whereas first order
neuroendocrine loops are dominating in most invertebrates. There is a trend in the
invertebrate series of increasing complexity in the higher phyla in terms of the
numbers of neuro- and classical hormones and the number of physiological
functions they regulate.
1
Because we already have an excellent vertebrate endocrinology course in our
school, the common lectures on endocrinology will focus primarily on
invertebrates.
Coelenterata
Overhead: LD1-1 (hydra)
The coelenterates is the most primitive phylum with known endocrine system.
This system consists exclusively of 1st order neuroendocrine loops. No classical
endocrine glands are known.
What you see here is a diagram of a freshwater coelenterate, the Hydra.
These animals produce a surprisingly rich collection of chemical signaling
substances, including a number of catecholamines, “vertebrate neuropeptides,”
and some novel peptides.
Overhead: LD1-6 (neuropeptides in hydra)
This figure shows the distribution of several neuropeptides, we recognize in
mammals, in the Hydra.
a) oxytosin/vasopressin
b) CCK
c) Substance P
d) Neurotensin
e) Bombesin
f) FMRFamide
I should say that the evidence for presence of these substances is based on
crossreactivity with antibodies to the mammalian peptides. I do not know if any of
these peptides have actually been isolated or their genes cloned from coelenterates.
Also, the biological effects of these neuropeptides in coelenterates remain
enigmatic.
Overhead: text (head activator)
The most fundamental and potentially significant aspect of coelenterate
endocrinology pertains to some peptides with morphogenic effects. A compound,
named head activator peptide has been isolated and sequenced (Glp-Pro-Pro-GlyGly-Ser-Lys-Val-Ile-Leu-Phe). Interestingly, the identical peptide has been
sequenced from mammals, including humans.
In the Hydra, the head activator influences head and bud formation, stimulating
the elaboration of these structures when present in very low concentrations. It is
2
also stimulating regeneration of the head region if it is severed. At the cellular
level, the head activator functions as a mitogen or growth hormone, stimulating
cells in G2 phase of the cell cycle to proceed through mitosis. There is also
evidence for an involvement in control of determination of uncommitted stem
cells.
Overhead: text (other neuroendocrine roles)
In addition to the effects of the head activator on tissue growth and differentiation
it has been shown that the “vertebrate hormone” thyroxine promotes asexual
reproduction through budding
There are other apparent endocrine functions in coelenterates as well. Some of
these relate to feeding, but I will not get into that here.
Platyhelminthes
Overhead: A7-13 (Planaria)
Flatworms are more complex animals than the coelenterates, but they are still
considered very primitive invertebrates. Like many lower invertebrates, most
flatworms have a remarkable ability to regenerate lost body parts. This function
has been worked on to some extent in an endocrinological context.
Overhead: LD2-6 (chemical changes after sectioning)
Flatworms have neurosecretory cells while no classical endocrine glands have
been located. If you section off a piece of a planaria worm you will find increased
activity in neurosecretory cells. There will also be a number of other chemical
changes in the tissue surrounding the wound and this high activity will go on until
the tissue is completely regenerated.
This figure illustrates some of this increased activity in the area of the wound.
Early 5-HT peak, parallel with increased adenylate cyclase activity and increased
cAMP concentrations. Subsequently, there is a rise in intracellular Ca, which is
believed to trigger DNA synthesis in planaria. While DNA synthesis and cell
division may be directly attributed to 5-HT release, the increase in protein
sysnthesis rate is probably the result of a different neurohormone. This other
neurohormone may be dopamine because dopamine levels peak in the regenerate
from 12 to 18 h, which correlates well with the increase in RNA synthesis, which
starts 12 h after the sectioning and peaks at 18 h. Furthermore, dopamine
inhibitors (haloperidol; fluphenazine) significantly delay regeneration of tissue.
3
Overhead: text (“vertebrate hormones in plathyhelminthes)
Several studies have investigated a number of turbellarians for the presence of
hormones resembling those of mammals. In all these studies, the approach has
been to use antibodies raised against mammalian hormones. Thus, rather than
demonstrating the presence of the same hormone, the investigators have shown
that there are molecules in turbellarians with antigenic determinants that resemble
those of some mammalian hormones. Immunoreactivity against the following
hormones have been detected:
 ACTH (primarily in margins of cerebral ganglia and nerve chords)
 Somatostatin (variable distribution)
 Met-encephalin
Any functions of these possible hormones remain elusive.
Mollusca
We are now taking a big step up to some advanced invertebrates, the mollusks.
Neurosecretory hormones are important in 1st order responses and also some 2nd
and 3rd order neuroendocrine systems. Much molluskan endocrine research has
been devoted to the reproductive system. At present, the endocrine control of
reproduction only of gastropods and cephalopods is known in some detail.
Reproduction of mollusks is extremely diverse and its control is complicated. For
example, many mollusks are protandrous hermaphrodites; young adults are males,
followed by a phase during which both sexes are present simultaneously. In the
final phase these snails have degenerated their male sex organs and become fully
female.
Overhead: B10-10 (prosobranch)
This is a prosobranch, namely the marine keyhole limpet. In many aspects,
prosobranchs are among the most primitive mollusks. The majority of the
prosobranchs are protandrous hermaphrodies. Sex reversal from males to females
has received a great deal of attention.
Overhead: LD mollusks 1-1 (reproductive systems); 1-2 (neuroendocrine
system)
The juvenile gonad of protandric snails is bisexual. At sexual maturity, the gonads
develop into testis under the influence of an androgenic neuroendocrine factor
from cerebral ganglia. If this factor is absent, female gonads develop. Subsequent
sex reversal is induced by a feminizing factor that also is released from the
cerebral ganglia.
This is the “slipper shell” (Crepidula fornicata). The male accessory sex organs
consist of a sperm duct, seminal vesicles, and external sperm groove, and a non4
retractable penis. During sex reversal, these organs are rearranged into an oviduct,
receptaculum seminis, uterus, and vagina. These changes occur independently of
the conversion of testis into ovaries.
Differentiation of the penis is orchestrated by a neurohormone that is released
from the right pedal ganglia under the influence of external ‘masculinizing’
stimulation. This hormone is released into the hemolymph and seems to
accumulate in a specific haemal lacunae in the right tentacle.
The dedifferentiation or lysis of the penis, which occurs during the transition to the
female phase, is induced by a neurohormone produced by neuroendocrine cells
located in the mediodorsal area of the pleural ganglia. At the same time there is a
negative control of the activity in the cells of the area in the pedal ganglion that
produces the morphogenic factor responsible for penis differentiation.
Overhead: B10-16 (Pulmonates)
Pulmonate gastropods are more advanced than the prosobranchs and their
endorcrine system is also more complex. We will look at the reproductive
endocrinology of two suborders within the subclass pulmonata, stylomatophora
and basommatophora. Stylommatophora include terrestrial snails and slugs, like
Helix and Limax. Basommatophora are the most primitive pulmonates and they
are primarily freshwater forms, such as Lymnaea. There are a few marine species,
such as marine limpets, Siphonaria.
Overhead LD p.142 Fig. 1 (Lymnaea)
The drawing on top is an illustration of the basommatophoran, Lymnaea stagnalis.
Overhead W11-15 (Pulmonates reproductive endocrinology)
Like the Prosobranchs, the pulmonates are typically hermaphrodites. While the
stylommatophorans (A) typically are protandrous hermaphrodites, basommatophoran species (B) are usually more simultaneous hermaphrodites (both sexes
at the same time).
Stylommatophora
In stylomatophora, the ovotestis is connected to the male and female assessory sex
organs by a hermatophroditic duct. The female and male reproductive tracts
diverge and may, or may not, re-fuse to form a common genital opening. The
female accessory sex organs are shown on top and the males below.
Dorsal body hormone (DBH) from the dorsal body (DB), which is under neural
control of the cerebral ganglia (CG), promotes vitellogenesis and functioning of
the female secondary sex organs. A secretion of the optic tentacles (OT) inhibit
female sex cell development and promotes male sex cell differentiation. A female
5
gonadal hormone (fgh) controls development of the female accessory sex organs
and a male gonadal hormone (mgh) regulates development of the male accessory
sex organs.
In basommatophoran snails the ovotestis is connected to the male and female
accessory sex organs via a hermaphroditic duct. The female and male reproductive
tracts diverge and the fertilization pocket may, or may not, re-fuse to form a
common genital opening. Again, the female system is shown on top and the male
organs below. Dorsal body hormone (DBH) from the dorsal body (DB) promotes
female sex cell development, vitellogenesis, and the development of female
accessory sex organs. Caudo-dorsal cell hormone (CDCH) from the caudo-dorsal
cells promotes ovulation, oviposition, and egg-laying behaviour. A secretion of the
lateral lobes (LL) promotes male sex cell maturation, most likely via stimulation
of a neurohormone from neurosecretory cells (NSC).
Overhead: LD p. 178, Fig. 33 and 34
CDCH from Lymnaea has been cloned and sequenced. It forms a part of a larger
precursor protein that is cleaved proteolytically into several neuropeptides. The
entire gene spans >10kb. CDCH has been found to be homologous to the EggLaying-Hormone (ELH) in Aplysia. Also, other hormones encoded in this
precursor show high degree of homology between Lymnaea and Aplysia.
Phylum Arthropoda
Class Crustacea
Overhead:Withers 11-16 (endocrine system of decapoda)
The crustacean endocrine system, like that of other higher invertebrates, has
neurosecretory cells and some classical endocrine glands. The following are the
principal endocrine areas.
1. The eye stalk contains a number of, so called, X-organs including medulla
externa (me), sensory pore, medulla interna (mi), and medulla terminalis (mt)
and the neurohemal organ, the sinus gland (sg). Axons from neurosecretory
cells in the brain and other parts of the nervous system pass to the sinus gland
via a neurosecretory tract.
2. The postcommisural organs receive axons from 4 neurosecretory cells in each
side of the circumesophageal connectives: only one is shown on the left side.
3. The pericardeal organs are located over openings of branchiocardiac veins into
the aorta: Numerous nerves run from the nervous system to the organs. The
dorsal nerve of the heart (n. dors) and nerves to muscles (n. mot) are also
shown.
4. The androgenic gland often is a vermiform mass of secretory cells attached to
the distal portion of vas deferens. The ovaries secrete female sex steroids in
many species.
6
5. The generalized neurosecretory system (except the eyestalk) consist of cerebral
neurosecretory cells (ns 1-5) and thoracic ganglia neurosecretory cells. Axons
of neurosecretory cells in all parts of the brain pass to the sinus gland, but only
axons from ganglionic neurosecretory cells pass out through the pedal nerves.
6. The Y-organ is an endocrine gland without innervation; it is an ovoid disk of
hypertrophied epidermis, which secretes molting hormone.
Overhead: Withers 11-17 (molting cycle)
Molting, that is the periodic shedding of the exoskeleton, is under endocrine
regulation in crustaceans as well as in other arthropods. The event of exoskeleton
shedding is termed, ecdysis, and names of the other phases in the molt cycle relate
to ecdysis. Thus, the molt period starts with the proecdysis, which leads into the
ecdysis. The period immediately following ecdysis is called metecdysis, and
periods between molts are called anecdysis.
1. During proecdysis, the epidermis starts to separate from the old cuticule
(exoskeleton) and the epidermal cells enlarge and begin to secrete the new
exoskeleton. Minerals and macromolecules are reabsorbed from the old
exoskeleton and temporarily stored elsewhere for later incorporation into the
new exoskeleton. Amino acids are stored in the hemolymph, while Ca is
deposited at various locations depending on species. The muscles of the major
limb segments atrophy during proecdysis so that the limbs can be pulled out
through the narrow basal segment at ecdysis. Regeneration of lost limbs also
begins during proecdysis.
2. At ecdysis, the old exoskeleton cracks open, typically in the rear end, and the
animal backs out of the old shell. When newly emerged, the new exoskeleton
is pale and soft. In many species the molted animal eats the old exoskeleton to
regain some of the minerals and other nutrients.
3. During metecdysis, Ca and other components are laid down in the new
exoskeleton and the limb muscles grow.
Overhead: LD p. 262, Fig. 4. (20-OH ecdysone in lobster)
Molting in crustaceans is induced by the steroid, 20-hydroxyecdysone, which is
produced and released as a precursor from the Y-gland. What this figure shows is
the concentration of 20-hydroxyecdysone in hemolymph of a lobster during the
molt cycle. The molting event, or ecdysis, is indicated by an M. The peak in 20hydroxyecdysone occurs just prior to the molt.
Overhead: LD p. 264, Fig. 8 (20-OH ecdysone in eyestalk ablated lobster)
There is however more to the story, because 20-OH ecdysone is not the only
hormone controlling molting. Already in 1905 there was a paper reporting that
bilateral ablation of the eyestalks of crabs accelerated the molting cycle.
7
This figure describes an eyestalk ablation experiment with lobster. Again, 20hydroxyecdysone concentrations in hemolymph were measured during the molting
cycle. One of the groups, represented by triangles, was eyestalk ablated here
(indicated by an “A”). Ablation substantially reduced the lag before the 20hydroxyecdysone peak and thereby also the time to molt.
Overhead: LD p.263, Fig. 6
The net effect of eyestalk ablation is pretty dramatic. This picture shows two
lobster siblings. The larger animal was bilaterally eyestalk ablated at the 2nd larval
stage and then kept under identical conditions during 5 months.
Overhead: Withers 11-16 (endocrine systems of crustaceans)
The explanation for this dramatic effects is that ecdysone release from the Y-gland
is under negative control of a peptide hormone, molt-inhibiting hormone (MIH),
which is released from the sinus gland of the eyestalk. MIH is a protein with a
molecular weight of 7000-9000, depending on species. MIH release, in turn, is
stimulated by a neurotransmitter, 5-HT. Exactly how the periodicity of molting is
regulated seems to be a matter of current research.
Reproduction
Already in 1943 it was demonstrated that the sinus gland is involved in
reproductive regulation as well. In a classic experiment, Panouse showed that
eyestalk ablation from prawn females leads to rapid increase in ovarian size and to
precocious egg deposition. The author further demonstrated that an ‘ovarianinhibiting factor’ was released by the sinus gland. The factor is now known to be a
peptide hormone with a MW of 7,000 – 8,000, and it is generally called, gonadinhibiting hormone (GIH). The sinus gland is the GIH-releasing organ, but the
source of this neurohormone is the medulla terminalis (mt) X-organ.
In females, the GIH level in the plasma varies during the course of the annual
reproduction cycle and ovary development is stimulated when the GIH
concentration of the hemolymph is low. In many species, sexual maturation and
molt cycle is synchronous. In such species, follicle growth and oocyte
development appear to be related not only to the absence of GIH but also to the
low levels of 20-OH ecdysone present at the beginning of each molt cycle.
Overhead: LD p. 292, Fig. 4 (vitellogenesis)
In all oviparous species that have been investigated, the yolk of the egg is not
produced in the follicle itself but elsewhere in the body and is transported to the
oocyte. The yolk protein is called vitellogenin (VTG) in arthropods and well as in
chordates. The process of vitellogenin production and its subsequent transport to
and uptake by oocytes is collectively called vitellogenesis.
8
In crustaceans, VTG synthesis occurs in an organ, called the fat body, and possibly
at other sites as well. VTG is transported in the hemolymph to the ovaries where
the protein is incorporated into the oocytes. The follicle cells that surround the
oocyte have an extensive tubular network through which the VTG molecules can
pass. Uptake of VTG in the oocyte occurs by means of receptor mediated
endocytosis.
There seems to be two targets for GIH: (1) Inhibition of VTG synthesis, and (2)
binding of VTG to the membrane receptors on the oocyte. When the level of GIH
in the hemolymph goes down the vitellogenesis can proceed, which leads to
maturation of the follicle.
Colour
Overhead: Withers 11-18 (crustacean chromatophores)
The colours of the crustaceans is given by pigments in the exoskeleton and by the
presence of chromatophores in the epidermis underneath. The chromatophores are
star-shaped cells, which contain pigments of different kinds. Red and yellow
pigments are carotenoids. The blue pigment of lobsters comes from carotenoids
bound to a specific protein. This protein is heat-labile, while the carotenoids are
not and this is the reason why blue lobsters turn red when you boil them. White
pigment is considered to be mainly pteridines with small amounts of purines. The
brown-black pigment, occurring in most crustaceans, is thought to be
ommochromes in most species. The otherwise commonly occurring dark pigment,
melanin, may not be present in crustaceans.
Most chromatophores are monochromatic and contain only one single type of
pigment. Polychromatic chromatophores contain two or several pigments.
Sometimes different chromatophores that each contain one pigment can be
organized very closely to each other so that they appear to be polychromatic; these
are called chromatosomes.
Many crustaceans are able to change colours to blend in with the background
environment. There are two types of colour change: (1) morphological and (2)
physiological. Morphological colour changes are slow and involve deposition of
pigment in the exoskeleton. Changes in the number of chromatophores, their
location, and pigment content are also considered to be morphological colour
changes. In contrast, physiological colour changes involve only alterations due to
redistribution of the pigment within the chromatophores. This process is usually
rapid, occurring in minutes or hours.
The pigment can be moved laterally out in the processes of the chromatophores
and, conversely be contracted in the center. When the pigment of a particular
chromatophor is dispersed the colouring effect of that chromatophor will
9
enhanced. For example, dispersion of pigment in a melanophor will give the
animal a dark appearance while pigment contraction will make the animal blanch.
Overhead: Withers 11-16 (endocrine system of crustaceans)
There is a dual regulation of each specific chromatophore type by pigment
dispersal and contracting hormones. Thus, there is a pigment dispersal hormone
and a pigment contracting hormone for each of the colours present. The sinus
gland is the main endocrine organ for regulation of dispersion and contraction of
pigment in chromatophores. Hormones inducing red pigment contraction and
white pigment contraction are also released in considerable quantities from the
post-commissural organ.
Overhead: text (pigment controlling hormones)
At least some of these hormones are oligo-peptides with amidated C-termini (red
pigment-concentrating hormone (RPCH: pGlu-Leu-Asn-Phe-Ser-Pro-Gly-TrpNH2).
In some crustaceans, there are general pigment dispersing hormones that affect
several different chromatophores. 5-HT, for example, has been found to produce
pigment dispersal in a wide variety of crustaceans, most often red pigment, but
dispersion of black and white pigments have also been reported. In the case of the
red pigment, the effect of 5-HT has been found to be indirect by promoting release
of RPDH.
Similarly DA produces red pigment concentration. Again this effect seems to be
indirect by stimulation of RPCH release.
NE has been found to produce red and black pigment dispersion in some species.
Again, the effect turns out to be indirect by stimulation of pigment dispersion
hormones.
Other hormones including Ach, histamine, octopamine, and GABA all have
effects on pigment dispersion or contraction, but in all cases the effects seem to be
indirect by release or inhibition of pigment dispersing or pigment concentrating
hormones.
Insecta
Of all invertebrates, the endocrinology is undoubtedly best described in insects.
Indeed, endocrine control of some physiological functions, such as molting, is
perhaps as well investigated as some mammalian systems. There are several
reasons for this progress in insect endocrinology. (1) Basic science: Insects are
pretty hardy animals, which allows you to carry out radical surgery, such as
10
parabiosis experiments where you join the front end of one individual to the rear
end of another. (2) Human health: Insects are sometimes vectors for diseases. (3)
Agriculture: There is also a strong financial incentive to work on insects in terms
of potential pest control.
Overhead: W11-20 (development in hemi- and holometabolous insects)
The processes of molting and pupation have been extensively studied in several
insect species and I will spend some time explaining the quite complex endocrine
regulation of these processes.
Like other arthropods, insects have exoskeletons, which they periodically have to
shed and renew in order to grow. Each larval stage, as separated by molts, is called
an instar. So before the first molt the larvae is a 1st instar, after the first molt it
becomes a 2nd instar, and so on. As you all know many insects such as moths have
larval and adult phases that are quite distinct. These phases are separated by a
pupa stage during which the metamorphosis from juvenile to adult form takes
place. Development including a pupa stage is called holometabolous development.
Many insects do not go through a pupa phase, but there is a gradual transition from
juvenile to adult morphology. Such a development is called hemimetabolous and is
exemplified here by the cockroach.
In insects with hemi- or holometabolous development the larvae goes through a
series of molts, but the adult stage is final and no more molts occur after that. A
few primitive insects continue to molt through the adult stage. Insects that
continue to molt as adults are called ametabolous.
Overhead: Withers 11-19 (CNS and endocrine system in an insect)
This figure shows the brain of a generalized insect and the major endocrine
systems involved in molting and metamorphosis. Corpora cardiaca and corpora
allata are two neurohemal organs which house the nerve terminals from several
neuroendocrine cells that have their cell bodies located elsewhere in the brain.
Nuclei for neuroendocrine cells include the median (mnc), lateral (lnc), and
subesophgeal (snc) neurosecretory cells.
The corpora allata are actually classical endocrine glands, which are somewhat
analogous to our adenohypophysis. The prothoracic gland is another important
classical endocrine gland.
Overhead: Eckert 9-34 (5 major developmental hormones)
Of the five major insect developmental hormones, three are produced by
neurosecretory cells and two by classical endocrine tissues. Median neurosecretory
cells synthesize prothoracicotropic hormone (PTTH). PTTH is synthesized in the
11
cell bodies of these cells, which are located in the protocerebrum, and transported
down to storage depots, or neurohemal organs, formed by the terminals of the
axons. The corpus cardiacum was previously thought to be the neurohemal organ
that stores and releases PTTH, but more recent evidence from the tobacco
hornworm moth indicates that the axons of the PTTH-producing neurosecretory
brain cells actually pass through the corpus cardiacum and end within the corpus
allatum. PTTH appears to be a small protein with a MW of about 5000.
Eclosion hormone (EC) is also produced and released by neurosecretory cells. EC
is a peptide that in contrast to PTTH seems to be released from corpora cardiacum.
Bursicon is the third neurohormone involved in molting. Also this hormone is a
protein. It is rather large with a MW of 40K and it is primarily produced and
released from neuroendocrine cells associated with the nerve chord. There is also
some production of bursicon in neurosecretory cells of the brain.
The two major players in molting are, however, not neuropeptides. These two
hormones are juvenile hormone (JH) which is a modified fatty acid, produced and
secreted by endocrine cells in corpus allatum, and ecdysone, which is produced
and released by the prothoracic gland in response to PTTH. As you know from our
discussion about crustaceans, ecdysone, is a steroid hormone. Furthermore, just as
in crustaceans, ecdysone is actually a pro-hormone that gets converted elsewhere
to the active form, which is 20-hydroxyecdysone. Ecdysone is sometimes called ecdysone and the street name of 20-hydroxyecdysone is ß-ecdysone.
Overhead: Eckert 9-36 (JH during different stages of development)
As the name implies, JH preserves the juvenile characters in the larvae. As long as
the JH concentration of the hemolymph is high at the time of molting, a larvae is
coming out of the molt. Now, the paradox is that in the adult moth JH is actually a
sex hormone, stimulating vitellogenesis and activating both ovarian follicles and
accessory sex glands. Consequently, the JH concentrations in the hemolymph have
to be high during each molt of the larval phase; to be metamorphosed into an adult
the JH must literally drop to zero; finally in the adult JH has to be upregulated
again to participate in the orchestration of sexual reproduction.
Overhead: Withers 11-21 (basic endocrine control of molting and
metamorphosis)
This is a very simplified diagram of the endocrine control of molting and
metamorphosis in a holometabolous insect, such as a moth.
PTTH, released from corpora allatum, act on the prothoracic gland stimulating it
to release ecdysone, which subsequently is converted to the active hormone, 20OH ecdysone. The role of 20-OHecdysone is to initiate the epidermal changes
12
necessary for molting and also to stimulate a change of the body tissues to adult
structures. However, JH from corpora allatum blocks the adolescence effect of 20OHecdysone. The result is that as long as there is a high level of JH in the
hemolymph, the larval characters are preserved; a low JH level, however, will
result in a pupa (in holometabolous insects). The metamorphosis to an adult in the
pupa requires that JH concentrations further drop to zero.
The question, now, is how are all these events coordinated?
Overhead: tobacco hornworm development (1, The Players)
What I am about to show you is a model of the endocrine regulation of larval and
pupal development. The model is based on information from the tobacco
hornworm, but probably applies to many other holometabolous insects as well.
Let’s first have a look at the “players”……
HSF is Hemolymph Stimulating Factor which is a proteinous hormone we have
not been talking about so far. In the tobacco hornworm, the synthesis of ecdysone
from the prothoracic gland is not only dependent upon PTTH stimulation, but
stimulation by HSF is also required. HSF is produced and released by the fat body,
which also is responsible for the conversion of ecdysone to 20-OH-ecdysone in
this species.
Overhead: tobacco hornworm development (2, Days 0-2)
On about days 1-2 of the last larval instar, the hemolymph concentration of JH
drops, setting into motion the endocrine cascade that drives larval-pupal
development. The decline in the JH levels occurs principally as a result of a
decrease in its synthesis by corpora allata (c.a.). The cue for this reduced JH
synthesis works via the brain to affect neural regulatory systems that inhibit the
production of JH in c.a. The decline in JH concentration results in an immediate
drop in the concentration of HSF level, thus, reducing its stimulatory effect on the
prothoracic gland to produce ecdysone. At this time the prothoracic gland (PG) is
actually not responsive to either PTTH or HSF, presumably because of a downregulation of PTTH receptors.
The drop in JH levels renders the PG competent to respond to both PTTH and
HSF. (JH inhibition of receptors?). However, because the PTTH and HSF
concentrations are low the ecdysone level remains low as well.
Before the larva has reached the point of pupa commitment, there is an inhibitory
feed-back of JH on PTTH neurosecretory cells in the brain. As a result of the precommitment drop in the JH titre, this inhibitory feed-back loosens up.
13
Overhead: tobacco hornworm development (3, Days 3-4)
Because the brake on PTTH synthesis is gone, there is a gated, episodic release of
PTTH on Day 3 of the instar. PTTH in turn acts on the now competent prothoracic
gland, in the presence of a low level of HSF, to elicit a subtle peak in ecdysone.
The ecdysone is converted to 20-OH-ecdysone in the fat body and it is this small
increase in 20-OH-ecdysone, occurring on Day 4 of the instar, that makes the larva
commit to become a pupa.
The pupal commitment peak in 20-OH-ecdysone elicits a typical wandering
behaviour of the larvae. It does not eat anymore and just hangs out while its tissues
are getting reprogrammed to enter the pupal stage. Another effect of this small but
crucial peak in 20-OH-ecdysone is a stimulation of JH production in c.a.
Overhead: tobacco hornworm development (4, Days 5-8)
This positive feedback causes the second JH peak during the last instar, which
serves to bring up the 20-OH-ecdysone concentration to the level required for the
tissues to change into a pupa. The JH peak results in very high HSF levels by
stimulation of the fat body. At this point, there is also believed to be a positive
feedback of JH on the synthesis of PTTH. The HSF together with high PTTH
concentration, in turn, boosts the production of ecdysone in the prothoracic gland.
The result of this hormonal interaction is very high ecdysone and 20-OH-ecdysone
levels culminating on Days 6-8.
Around Days 7-8 of the last instar, 20-OH-ecdysone starts to inhibit production of
JH from c.a. The effect is not direct, but mediated through stimulation of
inhibitory neurons in the brain. This inhibition will cause JH levels to drop at the
end of the instar.
Overhead: tobacco hornworm development (5, Days 8-10)
Will falling JH concentrations the HSF concentration will slowly drop. Although
the HSF concentrations still are high at this time the concentrations of ecdysone
and 20-OH-ecdysone start to gradually fall because of a reduced responsiveness of
the prothoracic gland to PTTH. The drop in ecdysteroid concentrations late in the
instar are not as rapid as the decline in JH levels but the ecdysteroid levels
continue to fall gradually up to pupation on Day 10.
There is a lot of more stuff on endocrinology in invertebrates (i.e. reproduction and colour change that may
be covered next time around)
14
15