Endocrine Abstracts

Differentiation of male reproductive system is guided by testicular hormones and growth factors secreted during fetal development under gonadotropin control. Disruption of testicular hormone production or action leads to gonadal dysgenesis and maldevelopment of external genitalia. Cryptorchidism and hypospadias are the most common birth defects in boys, and both conditions can arise as a consequence of anti-androgenic disturbance during development. Both of them are also assoc...

NECTAR (http://www.nectarcluster.eu/index.htm) is a cluster of EU-funded projects set up to investigate the potential impact of chemicals and pollutants on male and female reproductive health. NECTAR is coordinated by Andreas Kortenkamp. It was launched on May 1st 2008 and joins together the REEF (Reproductive Effects of Environmental chemicals in Female, coordinated by Paul Fowler), DEER (Developmental Effects of Environment...

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...

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...

Imatinib mesylate is a well-tolerated receptor tyrosine kinase inhibitor that has gained interest as a potential treatment for osteoporosis and other metabolic bone diseases. It is clinically approved for the treatment of chronic myelogenous leukaemia (CML), Philadelphia-positive acute lymphoblastic leukaemia and gastrointestinal stromal tumors (GIST), and targets the receptors for PDGFs, ABL-related gene, c-Abl, c-Kit and c-Fms. Altered bone and mineral metabolism has been de...

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...

BackgroundCentral hypothyroidism (CeH) is a rare condition affecting approximately 1:16000 – 100 000 individuals. Congenital forms can harm the normal development if not detected and treated promptly. The clinical and biochemical diagnosis especially of the isolated CeH can be challenging. The cases are not usually detected in the neonatal screening, which, in most countries, are focused on detection of the more prevalent primary hypothyroidism. Unt...

The thyroid gland produces thyroid hormones, which are essential regulators of growth, development and metabolism of the body and is mainly regulated by the thyroid stimulating hormone (TSH)/TSH receptor (TSHR) interplay. The TSHR couples to all four G protein families in vitro but only for the Gs and Gq signaling cascade a role has been identified in vivo. To gain further insights into the complex signaling networks mediated by G proteins in the thyroid, we generated...

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...