Gen. Pharraac. Vot. 12, pp. 429 to 43 I. 1981 0306-3623 81/060429-03502.00/0 Printed in Great Britain, All rights reserved Copyright © 1981 Pergamon Press Ltd

THE EVOLUTION OF HORMONAL SYSTEMS A REPORT ON THE LEOPOLDINA SYMPOSIUM 1981

ROBERT J. WALKER School of Biochemical and Physiological Sciences, Southampton University, Southampton, U:K.

{Receiced 7 April 1981)

L E O P O L D I N A S Y M P O S I U M - - T H E E V O L U T I O N O F

H O R M O N A L SYSTEMS

A symposium was held in the Schloss Reinhards- brunn, Thuringia, German Democratic Republic from the 22rid to the 26th March 1981 on the Evolution of Hormonal Systems. The symposium which was or- ganised by Professor M. Gersch, (Jena) and Professor P. Karlson, (Marburg) was held under the auspice of the Deutsche Akademie der Naturforscher Leo- poldina and will be published in an edition of the Nova Acta Leopoldina N.F. The Deutsche Akademie der Naturforscher Leopoldina was founded in 1652 as a society for all German speaking scientists and as such is older than the Royal Society of London. The Society has its permanent headquarters in Halle at August-Bebel-Strasse 50a, 4020 Halle.

The symposium was attended by about 80 scientists from Czechoslovakia, France and the United King- dom as well as from all over Germany. There were three main sessions, general aspects of hormonal evo- lution, evolution of peptide hormones, and the evolu- tion of terpenoid hormones. In addition there were two round table discussions, one on the possible path- ways in the evolution of terpenoid hormones and one on peptides in the evolution of the hormonal system. After some introductory remarks by the vice-Presi- dent of the Leopoldina, the first session was opened with a talk by Professor Karlson who introduced the idea of hormones from the initial concept of hormo- nal substances from the early experiments of Pro- fessor Starling in 1905, leading to the concept of neurohormones from the work of Professor Scharrer in 1928. He discussed the relative values of the terms neurotransmitter, neuromodulator, neurohormone, hormone, autocoid etc. He considered that progress in comparative endocrinology as well as in functional endocrinology was important in providing clues as to the possible evolution of hormonal systems. This was followed by a lecture on the hormonal control of metabolism in insects by Dr Goldsworthy (Hull). Attempts have been made using antibodies raised against vertebrate peptide hormones to identify such hormones in insects but those insect peptides so far isolated do not show any structural similarity to verte- brate hormones. Dr Goldsworthy discussed the roles of hyperglycaemic and adipokinetic hormones in the control and regulation of energy metabolism. The evolution of neurosecretory cells and systems was reviewed by Professor Oksche (Giessen). Professor Oksche considered peptide hormones to be very primitive in terms of evolution and suggested that

neurones might have evolved from neurosecretory type cells. He discussed the value of the central ner- vous system of Lumbricus as a model for the interac- tion between neurones containing amines with neur- ones containing peptides. He discussed the role of the neurosecretory cells in the vertebrate hypothalamus: In anatomical and function terms Professor Oksche considered that the reptillian brain was of great value in the comparison of avian and mammalian neuro- endocrine systems. Professor Gersch (Jena) concluded the afternoon programme with a lecture on the evolu- tion of peptide neurosecretion in invertebrates. He reviewed the widespread occurrence of neurosecretory cells in the central nervous system of invertebrates, linking this with the presence of neurohaemal organs.

On the Monday Dr Gerisch (Munchen) reviewed his work on the slime mould Dictyostelium and the role of cAMP in its ability to aggregate. He discussed the possible mode of action of cAMP in this species. cAMP stimulates the differentiation of cells from the growth phase to the aggregate competent stage. The most efficient stimuli for this process are repeated pulses of cAMP. One cell surface marker which is characteristic of aggregate competent cells is a glyco- protein which is probably involved in cell adhesion. cAMP pulses control the expression of this glyco- protein. When the cells are stimulated with cAMP, there follows a rise in intracellular cGMP level and there is an influx of calcium. Dr Schaller (Heidelberg) then gave a most interesting account of her work on the factors regulating regeneration in Hydra, includ- ing the information that she knew the amino acid sequence of the head activating agent in Hydra and that a similar peptide was present in the vertebrate hypothalamus. However the function of this peptide in the vertebrate central nervous system was un- known. This was followed by an account of the local- isation of vertebrate neuropeptides in invertebrates using immunocytochemical techniques by Dr Remy (Bordeaux). It is clear that vertebrate neuropeptides or closely related substances have a very wide distri- bution in invertebrate phyla but relatively little is known of their functions in these animals. The pep- tides so far identified include adrenocorticotrophic hormone (ACTH), arginine vasotocin, bombesin. bovine pancreatic polypeptide (BPP), cholecystokinin (CCK), enkephalin, ~-endorphin, fl-endorphin, gas- trin, glucagon, insulin, :t-melanotropin (ct-MSH), neurophysin, neurotensin, oxytocin, secretin, somato- statin (SRIF), Substance P, thyrotropin releasing hor- mone, vasoactive intestinal peptide (VIP) and vaso- pressin.

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430 ROBERT J. WALKER

In the afternoon Professor Pearse (London) dis- cussed and APUD concept, that is, the presence of cells which contain an amine, are able to take up an amine precursor, contain an amino acid decarboxy- lase and also contain peptides. These cells may also contain a nonspecific esterase or cholinesterase. There are now over 40 of these cells and whatever their individual origins the cells possess true endocrine functions and Professor Pearse considers that they constitute a third, neuroendocrine, division of the ner- vous system. Dr Wallis (Brighton) then reviewed the mechanisms for the molecular evolution of growth hormone, prolactin and other adenohypophyseal hor- mones. Comparison of the amino acid sequences of growth hormone and prolactin, from a single species, shows identity between about 25~o of all residues which strongly suggests a common evolutionary ori- gin. The growth hormone/prolactin family shows remarkable variability in evolutionary rates which is in contrast to most protein families where the evolu- tion rate is generally constant. The average rate of evolution in the line leading to human growth hor- mone is at least ten times faster than that in the non- primate growth hormone lines. This talk was followed by another biochemical lecture on the molecular evo- lution of neurohypophyseal hormones and neurophy- sins by Professor Acher (Paris). These two talks rep- resented a very comprehensive review of the evolution of these hormones through the vertebrate groups. Finally Professor Jaenicke (Koln) presented some of his data on sex induction in Volvox, this being in place of a talk on evolutionary aspects of the pleio- tropy of peptide hormones by Professor Schwyzer (Zurich) who was unable to attend. After dinner the final event of the day was a round table discussion on Peptides in the evolution of the hormonal system, chaired by Professor Gersch. Topics discussed in- cluded the link between receptor and hormonal evo- lution and the possibility that neuropeptides have dif- ferent functions in different groups of animals.

On the third day the symposium was opened by a review on neurotoxins from sea anemones by Dr Beress (Kiel) which replaced the lecture by Dr Dock- ray (Liverpool) on evolutionary relationships of gut hormones and neuropeptides. The anemone toxins can have very potent actions on excitable cells and can act in a variety of ways. This was followed by a talk by Dr Walker (Southampton) on aspects of research on neurohormones and neurotransmitters in invertebrates. Possible evolutionary relationships between invertebrate hormones so far identified chemically were discussed followed by a review of the central actions of neuropeptides from insects and molluscs. The interactions between neuropeptides and neurotransmitters was reviewed and possible evolu- tionary aspects of the occurrence of vertebrate pep- tides in invertebrates considered. Finally the role for a number of neurotransmitters as more long term neur- omodulators was discussed. Dr Teschemacher (Gies- sen) then reviewed the role for endorphins in the brain and their relationship with opioid receptors. He considered possible physiological roles for fl-casomor- phins in milk and their action on calves. It would appear that certain endorphins are released under emotional or physical stress. Finally before lunch Professor Oehme (Berlin) reviewed the physiological

roles for Substance P in association with pain and nociception.

In the afternoon there was an excursion to the cas- tle of Gotha, where, following a tour of the castle and library, a concert was held in a theatre in the castle.

The evening session was devoted to terpenoid hor- mones and composed two lectures. Professor Jaenicke (Koln) reviewed the various types of hydrocarbon gamones which he has isolated from a variety of spe- cies. Highly unsaturated C8 and C l l hydrocarbons act as gynogamones in the sexual cycle of brown algae. In, for example, the Fucales, the attractant of the spermatozoids is fucoserratene, 1,3cis,5trans-octa- triene. In the Ectocarpales and Laminariales the attractants are alicyclic C l l hydrocarbons with one or two side chains, for example, butenyl-cyclohep- ta-2,5-diene and vinyl,butenyl-cyclopent-3-ene. It is suggested that there is a common biogenetic pattern for these compounds, synthesis from unsaturated fatty acids by cyclizing proxidations. Professor Jaenicke has characterised the binding sites on the gametes. Dr Sehnal (Prague) provided a very comprehensive review of the Juvenile hormone in insects discussing in full the various roles that it plays in insect develop- ment. He also discussed the changes in Juvenile hor- mone function during evolution in this class.

On the morning of the last full day of the sym- posium there was a session on steroid hormones. Firstly the biosynthesis was very comprehensively reviewed by Dr Rees (Liverpool). He discussed the extent to which the various animal groups could syn- thesise steroids, observing that many invertebrates cannot synthesise sterols from acetate and mevalonate since the pathway is generally blocked at the C15 stage, farnesol. Although most steroid hormones come from cholesterol by side chain cleavage, the ecdysteroids of arthropods have a C27 skeleton. C21 and C19 steroids and oestrogens occur widely in invertebrates. The inactivation of steroids was reviewed by Dr Koolman (Marburg) while Professor Hoffmann (Strasbourg) considered the role of ecdy- sone in insects. The control of the circulating levels of steroids is achieved by the regulation of synthesis in the endocrine gland. Steroid hormones are relatively hydrophobic and catabolic reactions besides inacti- vating the hormone also make the molecule more hydrophilic. Steroid catabolism is similar in both ver- tebrates and insects. Following coffee Professor Ches- ter-Jones (Sheffield) was to have lectured on the evo- lution of hormones from the adrenal cortex but unfor- tunately illness prevented him from attending the symposium. But his paper will be published in the proceedings of the symposium. In his place Professor Hanke (Karlsruhe) lectured on the adrenal cortex, in terms of factors regulating its physiology and reviewed its biological functions. This was followed by Professor Baulieu (Paris) who discussed the inter- action between steroid hormones with their receptors and reviewed the isolation of these receptors. Pro- gesterone has been found to decrease adenylate cyc- lase activity in Xenopus oocyte membranes which re- produces the effect observed with intact cells. He presented evidence which indicated that the stereo- chemical specificity is different between soluble intra- cellular steroid receptors of most target cells and the membrane sites of Xenopus oocytes.

The evolution of hormonal systems 431

In the afternoon Professor Schutz (Heidelberg) reviewed the control of transcription by steroid hor- mones in the chick oviduct of the lysozyme gene. The steroid controlled rate of synthesis of egg-white pro- teins is closely correlated with the cellular concen- tration of egg-white protein mRNAs. Professor Beato (Marburg) then talked about protein induction by steroids hormones. Steroids act at the level of the genome and he discussed the events which occur in the genome. Experimental evidence supports the hy- pothesis that the steroid hormone receptors recognise specific nucleotide sequences in the neighbourhood of hormone dependent genes. He discussed general models for gene regulation. In the evening there was a discussion on the evolution of terpenoid hormones under the guidance of Professor Karlson.

On the final morning there were two lectures fol- lowed by a general discussion. Professor Buckmann (Ulm) reviewed the phylogeny of hormones and hor- monal systems. He suggested the possibility of a com- mon ancestor between fungi and animals and dis- cussed the possible evolution of various vertebrate hormones within invertebrate phyla. He postulated

that multiplicity and variability of functions might be inherent features of hormonal mechanisms and that a change in hormonal function during ontogeny or phy- logeny might be relatively easy. Finally Dr Richter (Jena) reviewed the various ways in which cells can communicate with one another, for example, via hor- mones, modulators or transmitters. He concluded that it was not possible to clearly separate these dif- ferent roles for a compound and that such names were artificial and that one should talk about the hor- monal, modulatory, transmitter function of a particu- lar substance.

The symposium provided an excellent opportunity for the exchange of ideas between scientists interested in the evolution of hormones and related substances. The published material from the symposium includ- ing both the talks and the discussions will provide a very comprehensive review of the subject and a useful basis for future work. It will also be of great value to people wishing to become aquainted with this area of research. Professor Gersch and Professor Karlson are to be congratulated for their decision to organise this symposium.