G-protein-coupled receptor kinases (GRKs) are implicated in the pathophysiology of human diseases such as arterial hypertension, heart failure and rheumatoid arthritis. While G-protein-coupled receptor kinases 2 and 5 have been shown to be involved in the desensitization of the rat thyrotropin receptor (TSHR), their role in the pathophysiology of hyperfunctioning thyroid nodules (HTNs) is unknown. Therefore, we analyzed the expression pattern of the known GRKs in human thyroid tissue and investigated their function in the pathology of HTNs. The expression of different GRKs in human thyroid and HTNs was measured by Western blotting. The influence of GRK expression on TSHR function was analyzed by coexpression experiments in HEK 293 cells. We demonstrate that in addition to GRKs 2, 5 and 6, GRKs 3 and 4 are also expressed in the human thyroid. GRKs 2, 3, 5 and 6 are able to desensitize the TSHR in vitro. This GRK-induced desensitization is amplified by the additional over-expression of beta-arrestin 1 or 2. We did not find any mutations in the GRKs 2, 3 and 5 from 14 HTNs without TSHR mutations and Gsalpha mutations. The expression of GRKs 3 and 4 was increased in HTNs independently from the existence of TSHR mutations or Gsalpha mutations. In conclusion, the increased expression of GRK 3 in HTNs and the ability of GRK 3 to desensitize the TSHR in vitro, suggest a potential role for GRK 3 as a negative feedback regulator for the constitutively activated cAMP pathway in HTNs.
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C Voigt, HP Holzapfel, S Meyer, and R Paschke
GÜNTHER SACHS, KLAUS-DIETER VOIGT, and J. C. BECK
Letzter Hasenpfad 63, 6000 Frankfurt 70 a.M., Federal Republic of Germany, * Medical University Clinic, Department of Clinical Chemistry, Martinistrasse 52, 2000 Hamburg 20, Federal Republic of Germany, and † The Robert Wood Johnson Foundation, Suite 310, Parnassus Heights Medical Buildings, 350 Parnassus Avenue, San Francisco, California 94117, U.S.A.
The increase in size of national and international scientific meetings has posed challenges to their efficient and effective organization. In planning the scientific programme, particularly when a process of abstract selection involves the judgement of multiple referees, new procedures should facilitate administration and reduce overall costs. The International Congress of Endocrinology held in Hamburg, Germany, in 1976, utilized a computer-assisted series of steps in handling abstracts and this paper summarizes the observations arising from the processing of over 1500 abstracts. We believe this experience will be valuable to future Congress organizers.
The objective of the process was the preparation of a
