Endocrine Abstracts

We have earlier shown that treatment with gonadotropin releasing hormone antagonist blocked adrenocortical tumour progression through gonadotropin suppression in inhibin α/SV40 T-antigen (inhα/Tag) transgenic (TG) mice. Hereby, we investigated the molecular mechanisms underlying the GnRH antagonist (Cetrorelix acetate; GnRH-a) treatment induced potential antitumor effects on gonadal somatic cell and adrenocortical tumors in vivo and in vitro. In...

FSH receptor (FSHR) expression has been shown in gonadal tumours, as well as in endothelial tumour vessel cells of various cancers. FSHR, due to its transmembrane localization could be a good candidate for receptor-mediated targeted cancer therapy. In recent years, a number of membrane disrupting lytic peptides have been used for receptor-based cancer therapy. In the present study, we characterised the specificity and cytotoxicity of a lytic peptide Phor21 conjugated to three ...

Expression of the follicle-stimulating hormone receptor (FSHR) has been shown in gonads, gonadal tumors, and in endothelial tumor vessel cells of various cancers. We investigated the specificity and cytotoxicity of a fusion lytic peptide Phor21, conjugated to different FSHβ-chain fragments to ablate FSHR expressing cancer cells in vitro and in vivo. Cytotoxicity of 12 different Phor21-FSHβ conjugates was tested in HEK-293 cells, stably transfected w...

The adrenal cortex is a dynamic organ that undergoes self-renewal. In the mouse it is divided into two concentric layers, the outer zona glomerulosa (ZG) and the inner zona fasciculata (ZF), that secrete aldosterone and corticosterone, respectively. Capsular and subcapsular stem/progenitor cells differentiate and migrate in a centripetal fashion to repopulate the gland until they reach the juxtamedullary region where they undergo senescence and apoptosis. Our lab has previousl...

Prepubertally gonadectomized (GDX) wild-type DBA/2J mice develop adrenocortical neoplasms presenting with small spindle-shaped non steroidogenic A-cells and large lipid-laden, steroidogenic and mitotically active B-cells. Neoplastic B-cells overexpress estrogen receptor α (ERα, Ers1) and β (ERβ, Ers2), aromatase (CYP19a1) and produce sex-steroids, resembling gonadal rest tissue. To test the role of estrogen-ER system in adrenocortical tumor progression, GDX...

The role of luteinizing hormone (LH) and its receptor (LHCGR) signaling in the adrenal gland remains unknown. Gonadectomy-induced chronically elevated LH levels trigger neoplastic transformation in genetically susceptible mouse strains (DBA/2J) or transgenic mice expressing the Simian Virus 40 T antigen (SV40Tag) oncogene under inhibin-α promoter (inhα/Tag). In order to study the functional role of LHR and GATA4 in the onset and progression of adrenocortical tumors i...

: We analyzed the occurrence of adrenocortical tumors in transgenic mice expressing Simian Virus 40 T antigen (SV40Tag) under the inhibin-α promoter (inhα/Tag) and searched for novel biomarker genes for the tumorigenesis. We studied 2-, 4-, 6-mo-old intact (never forming tumors) and prepubertally gonadectomized (GDX) inhα/Tag mice (developing tumors) and similar groups of wild-type mice as controls. Furthermore, the role of ectopic luteinizing hormone receptor (...

Adrenocortical tumorigenesis in prepubertally gonadectomized (GDX) DBA/2J mice has been attributed to chronically elevated luteinizing hormone (LH) and ectopic expression of luteinizing hormone receptor (LHCGR) and GATA-4 transcription factor. We analyzed now the mechanistic role of LH-LHCGR activation in GDX-induced adrenocortical tumorigenesis in intact and ovariectomized (OVX) wild-type (WT) and Lhcgr-/- mice in the DBA/2J genetic background mice, or by ...