a b s t r a c tExpression of the two gonadotropin-releasing hormone homologue peptides GnRHI and GnRHII and their receptor GnRHR has been demonstrated in a number of malignancies. In hormone-dependent breast cancer, GnRH analogs are used for therapy in premenopausal women. Gene expression of GnRHI, II and R was studied in breast biopsies from primary breast adenocarcinoma obtained from the tumor and the adjacent benign tissue. Levels were evaluated by a multiplex real-time RT-PCR. GnRHI transcripts were detected in 14.7% of the benign and 29.4% malignant biopsies and GnRHII in 21.2% benign and 44.1% malignant biopsies. GnRHR was also more frequent in the malignant (54.2%) than in the benign (24.0%) biopsies, at similar expression levels. No transcripts were detected in biopsies from healthy individuals. There was a strong correlation between the presence of GnRHI and GnRHII transcripts and their receptor in the benign and the malignant biopsies. GnRHI, II and R expression correlated significantly with poor prognosis pathological parameters. Immunohistochemistry for GnRHR revealed expression in malignant cells and in epithelial cells of mammary ducts of the adjacent area with pre-cancerous features. In contrast, GnRH I and II peptides were rarely expressed at low levels in breast cancer cells. In conclusion GnRH peptides and receptor are expressed more frequently in breast tumors than in the adjacent mammary tissue, representing a malignant feature. Their expression correlated to tumor characteristics of poor prognosis and was therefore related to more aggressive malignancies. Concomitant expression of peptides and receptor supports an autocrine/paracrine regulating role.

The corticotropin-releasing factor (crF) system plays a crucial regulatory role in the adaptation to exogenous and endogenous stress stimuli, as well as homeostasis. Apart from the central nervous system (cNs), the members of this neuropeptide family extend their actions in the periphery, where they may affect various body systems independently, stimulating peripheral crF receptors via vagal and/or autocrine/paracrine pathways. Here, we review all findings concerning the expression and role of the crF system in human liver, but also in other species. Direct and indirect regulatory data are also analyzed in order to draw conclusions about possible physiological/pathophysiological implications. Although data supporting any clinical significance are still limited and further research in the field is necessary, scientific interest in the crF system is particularly active, with multiple ongoing clinical studies evaluating the activity of crF ligands in medical conditions involving other organs. Thus, new knowledge with therapeutic potential appears to be steadily accumulating.

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oBJectIVe: the corticotropin-releasing factor (cRf) family consists of the neuropeptides cRf, ucn I, II and III and the binding sites cRfR1, cRfR2 and cRf-BP. It regulates stress response and the homeostasis of an organism. In this study, we examined the presence of the cRf system in the human hearts of normal and pathological fetuses. desIGn: Heart tissues from 40 archival human fetuses were divided into Group A (without pathology, 'normal'), Group B (with chromosomal abnormalities) and Group c (with congenital disorders). Immunohistochemistry was used to localize the cRf system. Results correlated to gestational trimester and pathology. ResuLts: Immunoreactivity for all antigens was found in cardiac myocytes of all groups, in almost all samples, except ucn III which was present in almost half of the fetuses of Groups B and c and was not detected at all in Group A. ucn III was more often present during the earlier stage of development (<21weeks) and in fetuses with congenital disorders. In a fetus diagnosed with heart pathology, all but ucn III antigens were also present. concLusIons: we localized a complete cRf system in the human fetal heart and correlated the presence of ucn III to development and pathology. More studies are needed to verify and clarify the exact role of the cRf system in the human fetal heart.

We localized a complete CRF system in the human fetal heart and correlated the presence of Ucn III to development and pathology. More studies are needed to verify and clarify the exact role of the CRF system in the human fetal heart.