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9th European Congress of Endocrinology


GH and prolactin at their targets

ea0014s10.1 | GH and prolactin at their targets | ECE2007

Cellular control mechanisms for GH sensitivity

Strous Ger , van Kerkhof Peter , van den Eijnden Monique , Putters Joyce

The growth hormone (GH) receptor is a key regulator of cellular metabolism. Using model cell systems we have investigated how GH-induced signaling is regulated, both in paracrine and autocrine conditions.Three features render GHR unique: (a) an active ubiquitination system is required for both endocytosis and degradation in lysosomes; (b) uptake of receptor is a continuous process, independent of GH binding and Jak2 signal transduction; (c) only cell sur...

ea0014s10.2 | GH and prolactin at their targets | ECE2007

GH receptor signalling

Norstedt Gunnar , Egnell Petra Tollet , Morales Amilcar Flores

GH receptor stimulation changes intracellular protein phosphorylation and activates the JAK-STAT signalling pathway. The JAK2 - STAT5 components of this pathway seem critical for growth. Factors of essence for cellular effects of GH include the duration of GH receptor stimulation and in different species there are sex differences in GH secretion where males have an episodic and females have a more continuous mode of GH secretion. At the cellular level, these two types of GH se...

ea0014s10.3 | GH and prolactin at their targets | ECE2007

Gene expression profiling of the antiangiogenic factor 16K human prolactin (hPRL) on endothelial cells underlines the key role of NF-κB and reveals novel mechanisms of action

Tabruyn Sébastien , Sabatel Céline , Nguyen Ngoc-Quynh-Nhu , Verhaeghe Catherine , Castermans Karolien , Malvaux Ludovic , Griffioen Arjan , Martial Joseph , Struman Ingrid

The 16-kDa N-terminal fragment of human prolactin (16K hPRL) is a potent angiostatic factor described to prevent tumor growth in mouse models. Using microarray experiments, we have dissected how the endothelial-cell genome responds to 16K hPRL treatment. Of the 23.000 transcripts present on the chips, 210 are regulated by 16K hPRL. Bio-informatic analysis and experiments performed on endothelial cells with various chemical inhibitors clearly suggest that NF-κB is crucial ...

ea0014s10.4 | GH and prolactin at their targets | ECE2007

Development of human prolactin receptor antagonists

Goffin Vincent , Rouet Vincent , Jomain Jean-Baptiste , Tallet Estelle , Kayser Christine , Kelly Paul A.

Experimental, clinical and/or epidemiological evidence points to a role for prolactin (PRL) in the promotion of benign and malignant tumors of the breast and the prostate. However, therapies reducing PRL levels (dopamine agonists) are currently not considered for the treatment of these pathologies. Dopamine agonists only target PRL secretion from the pituitary, while recent observations suggest that the involvement of autocrine PRL is perhaps even more relevant than circulatin...