Endocrine Abstracts

Strong gain-of-function mutations have not been identified in humans in the FSH receptor (FSHR), while such mutations are common among many other G-protein-coupled receptors. In order to predict consequences of such mutations on humans, D580 (D6.44) mutant forms of mouse (m) FSHR were expressed under the human anti-Müllerian hormone promoter in transgenic mice. Transgenic expression of mFshrD580H in granulosa cells led to abnormal ovarian structur...

BACKGROUND: Male steroidal contraceptive regimens achieve azoospermia in 60-90% of Caucasians. The mechanisms underlying this heterogeneity in response are not clear. The aim of this retrospective study was to examine a number of polymorphisms in genes involved in androgen metabolism and action, in azoospermic responders (n=73) and oligozoospermic non-responders (n=44) from previous contraceptive trials. METHODS: Local Ethical Committee approval was obtained. DNA was extracted...

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...

We have earlier shown a reciprocal feed-forward amplification link between expression of transcription factor GATA-4 and luteinizing hormone receptor (LHR) during adrenocortical tumorigenesis, and also that chronically elevated LH levels may induce LHR in mice, but not GATA-4. Hereby, our goal was to analyze the consequences of ectopically expressed GATA-4 on murine adrenal cortex in the presence and absence of gonadectomy (GDX) induced elevated LH levels. For this purpose, we...

The LH receptor (LHR) is a 7-transmembrane domain G-protein coupled receptor (GPCR) mainly expressed in the gonads with a major role in the development and maintenance of gonadal steroidogenesis and gametogenesis. Its ligand LH, secreted by the pituitary gland, binds to the extracellular domain of LHR triggering a conformational change in the transmembrane domain and leading to activation of intracellular signalling cascades.As a member of the GPCR famil...

Male transgenic (TG) mice overexpressing both the hCGα- and hCGβ- subunits present elevated levels of circulating hCG, Leydig cell hyperplasia/hypertrophy, elevated androgen levels and infertility (Rulli et al. 2003). In addition, serum FSH is significantly reduced in prepuberal and adult TG males compared with wild-types (WT), and does not change after treatment with the antiandrogen flutamide. The aim of this study was to evaluate the regulation of the hypot...

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...