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 ...

Progesterone (P4) treatment has been shown to have a clear modulating effect on murine Leydig tumor cell (mLTC-1) function, including downregulation of luteinizing hormone receptor. We hypothesized that P4 would stimulate, whereas an antiprogestine mifepristone (MF) block tumor progression in vivo in a transgenic (TG) murine Leydig cell tumor model (inhibin-α promoter-driven SV40 T-antigen (inhα/Tag)) and act similarly on cell proliferation in vitro...

Antiprogestine mifepristone (MF) has been shown to inhibit ovarian epithelial cancer (OEC) cell growth in vitro and in vivo. Recent clinical trials with MF for human OEC were unsuccessful, for unknown reasons. Progesterone (P4) is believed to have preventive measures towards breast, endometrial or hOEC cancers. Hereby we analyzed the effects of P4 and MF on ovarian granulosa cell tumorigenesis (GCT) in vitro and in vivo...

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...

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 ...