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A review of the role of neurosecretion in the control of juvenile

hormone synthesis: a tribute to Berta Scharrer

Barbara Stay

*

Department of Biological Sciences, University of Iowa, Iowa City, IA 52242, USA

Received 31 October 1999; received in revised form 31 December 1999; accepted 25 January 2000

Abstract

In the 1950s, Berta Scharrer predicted that neurosecretions from the brain regulated corpus allatum activity based upon the

observation of the change in localization of neurosecretory material in the brain and change in gland activity after severance of nerves

between the brain and corpus allatum. Isolation and characterization of neuropeptide regulators of juvenile hormone production by

the corpora allata in the late 1980s has confirmed this prediction. Both a stimulatory allatotropin and an inhibitory allatostatin have

been isolated from moth brains. Two families of allatostatins, both quite different from each other and that of moths, have been

isolated from cockroaches and crickets.

The wide distribution of these peptides in the nervous system, in nerves to visceral muscle, in endocrine cells of the midgut and

in blood cells, indicate multifunctions in the insects in which they are allatoregulatory. Some of these other functions have been

demonstrated in these insects and in insects in which these neuropeptides occur but do not act as corpus allatum regulators. For

the latter group, the neuropeptide regulators of the corpora allata have yet to be isolated. The families of neurosecretory regulators

will continue to grow.

2000 Elsevier Science Ltd. All rights reserved.

Keywords: Allatostatin; Allatotropin; Corpora allata; Juvenile hormone; Neurosecretion

1. Berta Scharrer’s experiment showing inhibitory

action of brain on corpora allata

Berta and Ernst Scharrer were founders of the concept

of neurosecretion. Their studies of invertebrates and

ver-tebrates, respectively, provided evidence for the

impor-tance and long evolutionary history of neuropeptides

(Scharrer and Scharrer, 1945, 1963). Berta Scharrer

demonstrated the neurohormonal regulation of the

corpora allata (CA) in experiments on the cockroach

Leucophaea maderae (Scharrer, 1952). After unilateral

severance of the nervi corporis cardiaci emanating from

the pars intercerebralis of the brain, she observed after

several

days:

(1)

accumulation

of

neurosecretory

material proximal to the cut, (2) disappearance of it

dis-tal to the cut and (3) enlargement of the corpus allatum

on the operated side. In the discussion of this paper she

noted that supernumerary molts of last instar nymphs

* Fax:+1-319-335-1069.

E-mail address: barbara-stay@uiowa.edu (B. Stay).

0965-1748/00/$ - see front matter2000 Elsevier Science Ltd. All rights reserved. PII: S 0 9 6 5 - 1 7 4 8 ( 0 0 ) 0 0 0 3 6 - 9

following this operation suggested brain regulation of

corpus allatum hormone. Furthermore, she assumed

from physiological effects and morphological change of

the glands that the “severance constitutes an increase

rather than a decrease in glandular activity.” In these

experiments Scharrer paved the way for the isolation and

characterization of the neurosecretory material in the

brain that could restrain, as in her experiment, or

stimu-late the production of juvenile hormone (JH).

2. Brain innervation of the corpora allata

(2)

clearer picture of the axon pathways from the brain to

the CA. In the cockroach Periplaneta americana this

method showed cells located in the contralateral pars

intercerebralis and the ipsilateral pars lateralis projecting

to the CA through the nervi corporis cardiaci (NCC) 1

and 2, respectively (Pipa, 1978). More recently,

Virant-Doberlet et al. (1994) found that two of the lateral cells

project contralaterally in the NCC2 to the CA in this

cockroach and in the cricket Gryllus bimaculatus. A

similar projection of protocerebral medial and lateral

cells was shown for the moth of the tobacco hornworm,

Manduca sexta, in which the NCC1 and 2 leave the brain

as one nerve (Copenhaver and Truman, 1986). These and

other retrograde diffusion studies identified the brain

cells whose products might influence juvenile hormone

synthesis by the CA.

3. Isolation of the neuropeptides affecting JH

production by the CA

This endeavor was much facilitated by the

measure-ment of JH production by CA in vitro, a method

developed by Pratt and Tobe (1974) after the structure

of JH was discovered (Ro¨ller et al., 1967) and methods

for purification of small amounts of material became

available. It was also spurred on by numerous

experi-mental demonstrations of brain regulation of the CA. For

all of the novel allatoactive peptides so far isolated, the

short-term radiochemical assay has been used to identify

the active fractions. However, identification of similar

peptides whether active in the species in which they were

found or not could then be achieved by immunological

or molecular biological techniques.

4. One identified allatotropin

The first allatal-active neuropeptide isolated was the

allatotropin of M. sexta (Kataoka et al., 1989), for which

the gene has now been cloned (Taylor et al., 1996). This

peptide has been isolated from and shown to be active

in a second (Spodoptera frugiperda) and possibly a third

lepidopteran, the tomato moth Lacanobia oleracea

(Table 1). The Mas-allatotropin has also been cloned in

Pseudaletia unipuncta and their CA show allatostatin

immunoreactivity to this peptide (Truesdell et al., 2000).

These data strongly suggest that the Mas-allatotropin is

also a true allatotropin in P. unipuncta. Originally found

to stimulate only adult CA (Audsley et al., 1999a,b), this

peptide is now shown, under favorable assay conditions,

to be active on larval CA of L. oleracea (Audsley et al.,

2000) and on CA of certain larval stages in the honey

bee Apis mellifera (Rachinsky and Feldlaufer, 2000;

Rachinsky et al., 2000). To date, this 13 amino acid

ami-dated peptide is the only allatotropin to be identified. It

occurs in M. sexta larval brain in one or two pairs of

ipsilateral lateral cells (1a

1

), two pairs of contralateral

lateral cells (III) and numerous axons in the corpora

car-diaca and corpora allata as shown by immunoreactivity

to antibodies against this peptide (Zitnan et al., 1995).

Immunoreactivity and in situ hybridization indicate that

the allatotropin occurs in other nerves of the central

ner-vous system and in frontal ganglion cells projecting to

the gut (Bhatt and Horodyski, 1999).

4.1. Allatotropins of unknown structure

Clearly there are other allatotropic neurosecretions to

be discovered. Some examples which have the potential

for success in isolation of allatotropins are given in

Table 2. The Galleria mellonella peptide has been

par-tially purified and an antibody against it developed

(Bogus and Scheller, 1996). The G. bimaculatus putative

allatotropin was extracted from subesophageal ganglia

(SOG) and is not species specific; it acts also on the

cricket Acheta domesticus (Lorenz and Hoffmann,

1995). As was found with the known allatotropin, the

actions of these putative allatotropins are stage specific

in their stimulation of the CA, and the CA of Locusta

migratoria require special incubation treatment for

suc-cessful stimulation by the allatotropin (Table 2).

4.2. Allatotropins from non-neural sources

Factors other than neuropeptides are known to

stimu-late JH synthesis. In the cockroach Diploptera punctata

the ovary stimulates increased JH production (Rankin

and Stay, 1984). Also, the ovary of G. bimaculatus

implanted into a male resulted in increased hormone

pro-duction by the CA, but extract of ovaries did not

stimu-late CA in vitro (Hoffmann et al., 1996). It remains to

be determined whether ovaries produce allatotropins that

act directly on the CA.

The male accessory sex gland of Drosophila

mel-anogaster produces a 36 amino acid peptide of known

sequence that, when transferred to the female during

mating, stimulates the CA, and does so also when CA

from virgin flies are incubated with this sex peptide in

vitro (Moshitzky et al., 1996). This peptide also acts as

an allatotropin on CA of the noctuid moth Helicoverpa

armigera (Fan et al., 1999). However, in the medfly

Cer-atitis capitata the Drosophila sex peptide stimulates CA

(3)

Table 1

The allatotropin of Manduca, Spodoptera, and Lacanobia: Gly–Phe–Lys–Asn–Val–Glu–Met–Met–Thr–Ala–Arg–Gly–Phe–NH2 Stimulation of CA

Species Isolation source/method No action on CA Reference

stage/concentration

M. sexta adult head adult/2·1029M larva Kataoka et al., 1989

chromatography, RCAa pupa

sequenced

S. frugiperda adult brain adult/1026M Oeh et al., 2000

chromatography, RCA sequenced

L. oleracea larval head adult/1025Mc larvad Audsley et al., 1999a,b, 2000 chromatography, ELISAb larva/1028M

not sequenced aRadiochemical assay for JH synthesis. b ELISA with antibody for Manduca allatotropin. cAudsley et al., 1999a.

d Audsley et al., 1999b.

Table 2

Examples of allatotropins of unknown structure

Species Source Stimulation of CA in vitro Reference

Galleria mellonella larval brain larval Bogus and Scheller, 1996

Pyrrhocoris apterus adult brain – SOGa–CC–CA adult, long day Hodkova´ et al., 1996 Gryllus bimaculatus

adult SOG adult, 0-day Lorenz and Hoffmann, 1995

Acheta domesticus

Locusta migratoria adult brain – CC adult, chilled 4°C, 24 h Lehmberg et al., 1992 aSubesophageal ganglion.

5. Three identified allatostatins

Mating in Drosophila stimulates JH production by the

female corpus allatum as a result of the transfer of

allato-tropic sex peptide. Mating in the cockroach D. punctata

also stimulates JH production, but it does so,

presum-ably, by signaling the brain not to release inhibitory

neu-ropeptide. Allatostatin (AST) is the name given to such

peptides and the first ones were isolated from D.

punctata brains (Woodhead et al., 1989; Pratt et al.,

1991). The three types of ASTs isolated thus far are

sum-marized in Table 3.

The M. sexta AST is a 15 amino acid non-amidated

pep-tide, completely different from the cockroach ASTs

(Kramer et al., 1991). The M. sexta AST inhibited CA

of adult Heliothis virescens (Kramer et al., 1991) and

also inhibited adult CA of S. frugiperda only after the

glands were stimulated by M. sexta allatotropin (Oeh et

al., 2000). A peptide that co-eluted with and had a

mol-ecular mass consistent with Mas-AST was isolated from

another lepidopteran, L. oleracea, but whether it is a true

AST in this insect is questionable because a much higher

concentration is required for its action than in M. sexta

(Audsley et al., 1998).

The cockroach allatostatins are a family of peptides with

a common pentapeptide amidated C-terminal sequence

and a variable number and sequence of amino acids at

the N-terminus. Several members of this family have

been isolated from other cockroaches in several different

families (Weaver et al., 1994; Belle´s et al., 1994) and

molecular characterization of the AST genes in these and

other cockroaches revealed that the gene sequence

con-tains 13 or 14 ASTs (Belle´s et al., 1999). Two members

of this Tyr–Xxx–Phe–Gly–Leu–NH

2

(YXFGL-amide)

family were isolated from the cricket G. bimaculatus

(Lorenz et al., 1995a) and a different family of ASTs,

four nonapeptides, were also found in this cricket

(Lorenz et al., 1995b).

The allatostatins have been shown to act on adult and

larval stages, and in D. punctata in embryos (Holbrook

et al., 1996). Several studies have shown that even

within one stage, the effect of the AST varies with the

physiological state of the CA (Pratt et al., 1990; Stay et

al., 1991a; Weaver, 1991). This is an important

consider-ation when assaying material for allatostatic or

allato-tropic action.

5.1. Localization of allatostatin in brain and other

tissues

(4)

Table 3

Isolated allatostatins

Structure/species Source(s) Inhibition of CA in vitro Reference

stage/concentration

pGlu Val Arg Phe Arg Gln Cys Tyr Phe Asn Pro Ile Ser Cys Phe–OH

Manduca sexta adult head larva, adult/2·1029M Kramer et al., 1991

Lacanobia oleracea larval brain larva/1025M Audsley et al., 1998

……Tyr/Phe Xxx Phe Gly Leu/Ile–NH2familya

Diploptera punctata adult brain and other tissueb larva, adult, embryo/

|1028M Woodhead et al. 1989, 1994; Pratt et al., 1989, 1991; Stay et al., 1991a; Holbrook et al., 1996

Periplaneta americana adult brain adult/|1029M Weaver et al., 1994 Blattella germanica adult brain adult/|1026–1027M Belle´s et al., 1994 Gryllus bimaculatus adult brain adult/|1028–1029M Lorenz et al., 1995a

Xxx Trp2…Gly7Gly8Trp9–NH 2family

Gryllus bimaculatus adult brain adult/|1028M Lorenz et al., 1995b

aThe cDNA for these cockroach species and three others indicates families of 13–14 peptides (Donly et al., 1993; Ding et al., 1995; Belle´s et al., 1999).

b CA, muscle extract, and hemolymph showed peptide coeluting with synthetic allatostatin (Stay et al., 1991b; Woodhead et al., 1992, 1993); midgut cells (Reichwald et al., 1994; Yu et al., 1995b) and hemocytes (Skinner et al., 1997) contain allatostatin mRNA.

immunocytochemically to be lateral protocerebral cells.

In M. sexta they are 1a

2

and 1b cells that project axons

to the ipsilateral CA with branching in the corpora

car-diaca and within the CA (Zitnan et al., 1995). In D.

punctata and G. bimaculatus it is also the lateral

proto-cerebral cells and the NCC2 that show allatostatin

immu-noreactivity which is seen in nerve branches in the

corpora cardiaca and the CA (Stay et al., 1992;

Neu-ha¨user et al., 1994). In addition to these cells that project

to the CA, there are interneurons in the brain (Zitnan et

al., 1995; Stay et al., 1992). As is indicated in Table 3,

the allatostatins of D. punctata were shown by isolation

or by the presence of mRNA in many tissues other than

the brain. Immunocytochemistry for these various

allato-statins show that they are widely distributed not only in

the central nervous system but also in peripheral nerves

to visceral muscle (e.g. Lange et al., 1993), in midgut

cells (e.g. Audsley et al., 1998) and in hemocytes

(Audsley et al., 1998; Skinner et al., 1997). Such a wide

distribution of the peptides suggests that they have

mul-tiple functions and some of these have been

demon-strated (see Section 6).

5.2. Peptides similar to allatostatins but inactive on

CA in the insect of origin

In view of the occurrence of ASTs in many tissues of

an insect in addition to brain cells innvervating the CA,

it is not surprising that peptides similar or identical to

those that do act as ASTs are found in insects, even other

arthropods, in which they do not act as allatostatins.

Examples of these are given in Table 4.

The M. sexta allatostatin is found in P. unipuncta, a moth

of a different family, but it is believed not to function

as a true allatostatin because at 10

26

M it inhibits JH

synthesis by CA of 5-day adult females only 60% and

does not inhibit larval CA (Jansons et al., 1996). It is

less surprising that M. sexta allatostatin does not inhibit

the CA of a dipteran, e.g. Drosophila (M.D. Price, R.

Nichols, P.M. Koladich, J. Merte, S.S. Tobe, W.G.

Bendena, unpublished). Also insensitive to the

cock-roach allatostatin-like peptides, YXFGL-amide, are the

CA of the dipteran Calliphora vomitoria (Duve et al.,

1993) and another fly Neobelleria bullata (Veelaert et

al., 1995) that are not innervated with allatostatin

immu-noreactive neurons. In general, it appears that CA

lack-ing innervation by nerves containlack-ing the allatostatin

being tested are not inhibited by that peptide. The CA of

the earwig Euborellia annulipes is another such example

(Rankin et al., 1998b). However, the locusts L.

migratoria and Schistocerca gregaria are exceptions to

this generality in that their CA do have allatostatin

immunoreactive neurons (Veelaert et al., 1995). Perhaps

assay conditions and/or CA stage were not ideal for

demonstrating an allatostatic effect of the schistostatins

(Veelaert et al., 1996).

5.3. Allatinhibins and allatostatins of unknown

structure

(5)

vitel-Table 4

Isolated peptides similar to allatostatins (AST), inactive on CA in insect of origin

Species Structure/name Reference

M. sexta AST

Pseudaletia unipunctaa identical Jansons et al., 1996 Drosophila melanogastera one a. a. different Price et al., unpublishedc Periplaneta americana coelutes with Audsley et al., 1998

– Tyr Xxx Phe Gly Leu–NH2

Calliphora vomitoria Leu/Met callatostatins Duve et al., 1993; Duve and Thorpe, 1994

Lucilia cuprinaa,b Leu-allatostatins East et al., 1996

Aedes aegyptib allatostatins Veenstra et al., 1997

Schistocerca gregaria schistostatins Veelaert et al., 1996; Vanden Broeck et al., 1996

Helicoverpa armigera helicostatins Duve et al., 1997a

Cydia pomonella cydiastatins Duve et al., 1997a

Carausius morosus cricket – type A Lorenz et al., 2000

Xxx Trp2– Gly7Gly8/Ala8Trp9–NH 2

Carausius morosus cricket – type B Lorenz et al., 2000 acDNA identification.

b Presumed to be inactive on CA of this species.

cM.D. Price, R. Nichols, P.M. Koladich, J. Merte, S.S. Tobe, W.G. Bendena, unpublished.

logenic cycles, for example in the viviparous cockroach

D. punctata (Rankin and Stay, 1985a), or at the end of

the last larval stadium, for example in M. sexta

(Bhaskaran et al., 1990). Bhaskaran and coworkers have

partially identified a factor from this stage larva of M.

sexta that provides stable inhibition until after

metamor-phosis, when glands are first treated in vitro with a brain

factor and then implanted into penultimate instar larvae

(Unni et al., 1993). They have called this brain factor

allatinhibin to distinguish it from the fast, reversible

action of allatostatins. The complete identification of this

factor will be important for understanding neuropeptide

regulation of the CA. Table 5 gives some examples for

other insects in which a search has begun for other

alla-tostatins. It will be of particular interest to learn what

this factor is in Drosophila since it has already been

demonstrated that M. sexta allatostatin is not active in

this species (M.D. Price, R. Nichols, P.M. Koladich, J.

Table 5

Examples of long-acting allatinhibin (AI) and short-acting allatostatins (AST) of unknown structure

Species Source/action Reference

Manduca sexta AI Brain-conditioned medium Unni et al., 1993

CA treated in vitro 16 h, long-term CA inhibition in vivo

Locusta migratoria AST Brain – CC extract Okuda and Tanaka, 1997

CA inhibited in vitro

Euborellia annulipes AST Brain extract Rankin et al., 1998a

CA inhibited in vitro

Drosophila melanogaster AST CNS extract P. Koladich (personal communication)

Sarcophaga bullata AST CA inhibited in vitro Richard et al., 1990; Altaratz et al., 1991

Merte, S.S. Tobe, W.G. Bendena, unpublished) and the

cockroach allatostatin is also likely not to be active since

it is inactive in the blow fly C. vomitoria (Duve et al.,

1993). Thus the Drosophila allatostatin may be a new

allatostatin.

5.4. Allatostatins of unknown structure, from

non-neural sources

(6)

syn-thesis by CA in vitro (Hoffmann et al., 1996). This was

reversible, dose-dependent and showed differential

potency on CA from different aged animals (Hoffmann

et al., 1996). In L. migratoria a partially purified ovarian

allatostatic peptide, with an apparent molecular weight

of 1–1.3 kDa, was also found to inhibit JH synthesis by

CA in vitro in a dose-dependent manner (Ferenz and

Aden, 1993). Further purification of this ovarian

allatos-tatin is underway (H.-J. Ferenz, H. Weinert, personal

communication).

6. Other functions of allatoactive peptides

Because the allatoactive peptides were isolated by

their action on JH production by the CA in vitro they

have been called allatostatins and allatotropins.

How-ever, demonstration of their distribution throughout the

insect of origin, in other insects and in other

invert-ebrates, clearly indicates that their function is not limited

to modulation of JH synthesis. Nerve terminals in

neu-rohemal organs, for example in M. sexta, allatostatin and

allatotropin immunopositive nerves in the corpus

car-diacum (Zitnan et al., 1995) and allatotropin

immunore-activity in the neurohemal transverse nerve (Veenstra et

al., 1994), indicate that these peptides could act

humor-ally. Direct innervation of the CA and muscles of the

gut suggest local action of the peptides in these locations

(see Section 5.1). Numerous examples of interneurons

and neuropile showing allatostatin immunoreactivity

suggest direct neuromodulatory function in the central

nervous system (e.g. Davis et al., 1997; Veelaert et al.,

1996; Yoon and Stay, 1995).

Demonstrated actions of allatoactive peptides other

than those on the CA are summarized in Table 6. These

include inhibition of muscle contraction by members of

the YXFGL-amide peptide family, shown in diverse

insects for several parts of the digestive tract and for

Table 6

Other functions of allatoactive peptides

Peptide Function Tissue Species Reference

M. sexta allatotropin Myostimulatory Heart M. sexta Veenstra et al., 1994

Inhibition of ion transport Midgut M. sexta Lee et al., 1998

YXFGL-amidea Myoinhibitory Hindgut muscle D. punctata Lange et al., 1995

allatostatin C. vomitoria Duve and Thorpe, 1994

E. annulipes Rankin et al., 1998b

Foregut L. maderae Duve et al., 1995

C. pomonella Duve et al., 1997b

Oviduct S. gregaria Vanden Broeck et al., 1996

Heart B. germanica Vilaplana et al., 1999

Inhibition of vitellogenin synthesis Fat body B. germanica Martin et al., 1996 Neuromodulatory Stomatogastric ganglion Cancer borealis Skiebe and Schneider, 1994 aTyr–Xxx–Phe–Gly–Leu–NH

2.

oviducts; and stimulation of heart muscle contraction by

M. sexta allatotropin reported for that insect (Table 6).

The M. sexta allatotropin has also been shown to rapidly

and reversibly inhibit ion transport across the midgut

epithelium in vitro in larvae of M. sexta (Lee et al.,

1998). A quite different function of YXFGL-amide

reported in Blattella germanica was inhibition of

vitello-genin production by fat body, apparently by inhibition

of glycosylation of the vitellogenin (Martin et al., 1996).

Previously reported putative allatostatin receptors in fat

body of D. punctata suggested action of allatostatin on

this tisuse (Cusson et al., 1991). The only experiments

demonstrating neuromodulatory action of an allatoactive

peptide were done with the crab Cancer borealis.

Anti-bodies against D. punctata allatostatin demonstrate the

presence of allatostatin-positive cells in the commisural

ganglion that send axons to the neuropile of the

stomato-gastric ganglion, where they ramify around the neurons

that control the rhythmic movements of the pyloric

stom-ach (Skiebe and Schneider, 1994). Allatostatin applied

to this ganglion strongly decreased the rhythmic

move-ments of the stomach in a dose-dependent manner

(Skiebe and Schneider, 1994). Members of the

YXFGL-amide family of peptides have been isolated and

sequenced from the crab Carcinus maenas (Duve et al.,

1997c). The distribution of allatostatin immunoreactivity

in the stomatogastric nervous system of several decapod

crustaceans suggests that these peptides function as

neu-rohormones as well as neuromodulators in these

crus-taceans (Skiebe, 1999).

7. Important on-going investigations

(7)

investi-gation in order to provide a complete understanding of

the regulation of the CA by neurosecretions.

Identification of the receptors for these peptides will

be important in demonstrating whether there are multiple

receptors and to what extent regulation of the receptors

conditions the sensitivity of the corpora allata to

allatos-tatins and allatotropins. Search for allatostatin receptors

has only begun (Cusson et al., 1991; Yu et al., 1995a).

The signal transduction pathways for the action of

allatoactive peptides will require further investigation.

Only a few studies have been done. The activation of

the inositol triphosphate pathway is implicated in the

action of M. sexta allatotropin on CA of M. sexta

(Reagan et al., 1992), as well as in the action of D.

punctata allatostatin on CA of D. punctata (Rachinsky

et al., 1994).

The target of action of allatoactive peptides in the

pathway of JH synthesis is also an important area of

ongoing research. Many studies have shown that

YXFGL-amide allatostatins act before the final steps in

JH synthesis (e.g. Pratt et al., 1989). It could be that the

transfer of two-carbon units from the mitochondria to

the cytoplasm is the target for allatostatin action in the

CA of D. punctata (Sutherland and Feyereisen, 1996).

Regulation of release of the allatoactive peptides is a

challenging area that will require investigating the roles

of internal and external signals that impinge on the

func-tioning of the CA. The interaction of many factors will

undoubtedly be revealed. For example, Berta Scharrer’s

severance of the nerve from the pars intercerebralis

released the corpus allatum from inhibition (Scharrer,

1952), yet the allatostatins of the cockroach are delivered

to the CA by lateral neurosecretory cells (Stay et al.,

1992). This suggests multiple neurosecretory influences

on JH production which could be regulated by different

signals. Much remains to be learned about the extent to

which neuropeptides participate in the regulation of JH

synthesis by the CA.

8. Conclusion

Only one allatotropin and three kinds of allatostatins

have been found, and only in Manduca sexta have both

an allatotropin and an allatostatin been identified.

Undoubtedly more stimulatory and inhibitory peptides

will be found. In the search for them it will be important

to consider the physiological state of the CA as well as

the conditions for assaying activity.

The allatoactive neuropeptides are not limited to

action on the CA. They occur not only in the brain but

throughout the nervous system, in the midgut cells and

in blood cells. This is not unexpected since, as Scharrer

pointed out in a retrospective review, a neuroendocrine–

gut axis is well known for vertebrates (Scharrer, 1990).

Clearly, the neuroactive peptides have multiple functions

and many of these have yet to be well characterized.

The peptides that have allatoactive function in one

insect may occur in others, but not act on CA in these

insects. These “false allatostatins” and “false

allatotrop-ins” could in some cases change their status under

differ-ent assay conditions.

Finally it is important to note that the allatoactive

pep-tides of insects are not limited to insects. They have been

found in crustaceans and will undoubtedly be found in

phyla other than arthropods. The relationship of these

molecules in their long evolutionary history will be an

interesting story which Berta Scharrer started, and in

which she took a keen interest throughout her long and

distinguished career. She would, I believe, be even more

delighted to learn of a worldwide study of neuropeptides,

including cockroach allatostatin, in crustacean ganglia,

an investigation being utilized to shed light on how the

human brain functions highlighted in the 1998 report of

Human Frontier Science Program (Strasbourg, France).

Berta Scharrer was a strong proponent of relating her

research on insects to a broad understanding of the

func-tion of neuropeptides.

References

Altaratz, M., Applebaum, S.W., Richard, D.S., Gilbert, L.I., Segal, D., 1991. Regulation of juvenile hormone synthesis in wild-type and

apterous mutant Drosophila. Molecular and Cellular

Endocrin-ology 81, 205–216.

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Gambar

Table 1The allatotropin of Manduca, Spodoptera, and Lacanobia: Gly–Phe–Lys–Asn–Val–Glu–Met–Met–Thr–Ala–Arg–Gly–Phe–NH2
Table 3Isolated allatostatins
Table 4Isolated peptides similar to allatostatins (AST), inactive on CA in insect of origin
Table 6Other functions of allatoactive peptides

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