BSCB Newsletter, Winter 2005

7th European Conference of Endocrinology
Gothenburg, Sweden, July 2005

The conference took place in the very modern and spacious convention centre in Gothenburg, Sweden's second largest city. Throughout the city run broad avenues and the bottom of almost every building seems to have been converted to a shop. Especially difficult for the unexperienced pedestrian were the countless trams, which luckily didn't go very fast.

By Nele Schwarz

The submission of over 1100 abstracts and the registration of delegates from 68 countries promised to make this an interesting meeting, the purpose of which was the exchange of generally new research in the endocrine field on a European basis.

Of special interest was the session 'Immune-endocrine interactions'. Clemens Kirschbaum (Techninal University, Dresden, Germany) gave an interesting overview of his work on the adrenal axis and psychological stress. He is trying to identify the link between psychology and stress, which factors are involved and how and why people react differently to stressful situations. He was able to identify sex differences between men and women involving the HPA axis before and during stress. Women have higher cortisol levels and therefore a higher initial sensitivity to stress than men. The cortisol levels in women, however, decline after the stressful event, whereas the intially low cortisol levels in men increase after stress.

Dr Kirschbaum proposed a signalling mechanism by which stress activates the translocation of NFkB into the nucleus where it causes an increase in transcription of inflammatory cytokines. This then leads to an increase in IkBa, a natural inhibitor of NFkB. This inhibitor is also directly activated by glucocorticoids, e.g. cortisol. Unfortunately, he did not speculate about the biological consequences of his findings; for example, whether the initially higher cortisol levels in women lead directly to higher levels of IkBa and therefore a lower level of proinflammatory cytokines before and during the first periods of stress, compared with men.

Another session I found highly interesting was 'Impact of endocrine disrupters on human health'. The first talk dealt with hormones and endocrine disrupters in food and water and was given by Bernard Jegou (University in Rennes, France). He defines endocrine disrupters as exogenous substances that cause adverse health effects in an intact organism or its offspring. Endocrine disrupters typically perturb 'normal' signalling pathways by mimicking or blocking endocrine hormones in cells rather than causing damage directly as chemical substances do.  Most hormones that occur in the environment are natural mammalian and plant hormones, but synthetic hormones as in the contraceptive pill and environmental contaminators, such as DDT, also play a role.   

There is a significant increase in naturally occuring mammalian hormones found in water, because of an increase in farming and the number of cattle kept world wide. In the USA and Europe, more than 500 tons of steriods (androgens, oestrogens and gestagens) are released per year by cattle alone. Including pigs, sheep and chicken, this number rises to 700 tons. Usually these hormones are 100-10000 times less active than endogenous hormones, but the high amounts in the environment and also the mixture of different hormones can still cause disruptive effects in organisms.

The second talk in that session was given by Werner Kloas (Leibniz Institute of Freshwater Ecology, Berlin). He studies amphibians as models of effects of endocrine disrupters in water, especially their reproduction and the thyroid system, which is of major importance for metamorphosis in amphibians. Most studies involving endocrine disrupters have been carried out studying animals living in water, mainly fishes. These studies found that oestrogens and anti-androgenic compounds cause feminisation while androgens lead to masculinisation and anti-oestrogens cause neutralisation due to underdevelopment of the gonads. In amphibians, endocrine disrupters can affect the reproductive system, leading to abnormal sexual development as mentioned above, but also the thyroid system, leading to accelerated or retarded metamorphosis.

Amphibians are a good model to study the disruptive effects of hormones, since hormonal effects can be detected easily and in some cases very early in the development of the organism. He then pointed out that the big variety of reproductive biology needs more comparative studies to investigate whether general endocrine principles do exist between amphibian orders, different classes of vertebrates and even other groups in the animal kingdom.

From the programme, the last day of the conference sounded the most related to my work, which is on G-protein coupled receptors. The first session started with Anna Spada (Institute of Endocrine Sciences, Milan) giving a talk on G-protein mutations. After a short overview, she focused on mutations in the a sub-unit of G stimulatory proteins. Most mutations in G-protein signalling have been identified in the receptor, but mutations in the a sub-unit, causing either a gain or loss of function, can lead to pathological phenotypes. For example, McCune-Albright syndrome is caused by an inactivating germ line mutation in the gene encoding the a sub-unit G stimulatory protein 1 (GNAS1), leading to osteodistrophy and pseudo-hypoparathyoidism. Receptor-activating mutations can increase cAMP concentrations and cause uncontrolled cell proliferation.

This session was followed by a symposium on G-protein coupled receptors - basic and clinical aspects.  The most interesting talk was given by Moritz Banemann (University of Wurzburg, Germany) on Spatio-temporal aspects of GPCR-induced G protein activation. Currently, there are two models of G protein coupling. The older model is termed free collision coupling, where the G proteins are free to diffuse within the membrane and coupling occurs at random, leading to slow signalling, whereas the second model proposes a pre-coupled state in which the heterotrimeric G protein complex (a, b and g sub-units) dissociates upon activation of the receptor by a ligand.  The kinetics and coupling mechanisms in living cells are studied using  fluoroscence resonance energy transfer (FRET) assays. Analysis of the FRET signal from interactions between the a2A-adrenergic receptor and labelled Gbg-subunits of Gi proteins suggested no significant pre-coupling between the receptor and G proteins.

When studying members of the G protein family in more detail, Dr Banemann's group found that the subunits Gai1, Gai2, Gai3 and Gaz do not fully dissociate upon activation of the receptor. They observed a rearrangement of the sub-units and found complete dissociation only for the highly homologous Gao sub-unit. The difference in sub-unit behaviour upon receptor activation is unfortunately still not known, but might represent a novel mechanism for subtype selective cell signalling.

In general, I found the conference rather dissapointing. Even though it was advertised as covering a broad range of endocrinological aspects, the main emphasis was on clinical studies. All the 'meet the expert' sessions were purely clinical, discussing whether or not radioactive iodine should be given before the age of 18 and insulin pump therapy in children and adolescents. Also, I felt that this conference had a strong 'bias' towards diabetes and obesity, two subjects which seem to be very popular in endocrinology at the moment. Nevertheless, I did learn some interesting things and would like to thank the BSCB very much for the opportunity to go to the conference, especially since Sweden is not known to be cheap!

Nele Schwarz
Centre of Molecular Endocrinology
Barts and the London
Queen Mary School of Medicine and Dentistry
n.schwarz@qmul.ac.uk