Searchable abstracts of presentations at key conferences in endocrinology

ea0049s21.2 | Environmental influences on endocrine systems | ECE2017

Evidence on reproductive disorders through endocrine disruption in-utero

Toppari Jorma

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...

ea0022s1.2 | European networks | ECE2010

NECTAR: network for environmental chemical toxicants affecting reproduction

Toppari Jorma

NECTAR ( 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...

ea0037ep1134 | Endocrine tumours | ECE2015

Gonadotropin releasing hormone antagonist treatment induces cell cycle arrest in gonadal somatic cell and adrenocortical tumours

Doroszko Milena , Chrusciel Marcin , Huhtaniemi Ilpo , Toppari Jorma , Rahman Nafis

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...

ea0035oc10.5 | Endocrine Tumours | ECE2014

Molecular mechanisms underlying the unexpected promoting effects of mifepristone on murine testicular Leydig cell tumorigenesis

Chrusciel Marcin , Ponikwicka-Tyszko Donata , Stelmaszewska Joanna , Li Xiangdong , Huhtaniemi Ilpo , Toppari Jorma , Wolczynski Slawomir , Rahman Nafis

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...

ea0022p68 | Bone/Calcium | ECE2010

Imatinib mesylate disturbs bone growth and remodellation in postnatal rats

Nurmio Mirja , Joki Henna , Kallio Jenny , Maatta Jorma , Vaananen Kalervo , Toppari Jorma , Jahnukainen Kirsi , Laitala-Leinonen Tiina

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...

ea0056gp49 | Adrenal medulla and NETs | ECE2018

Targeted destruction of FSHR-positive cancer cells by a lytic Phor21-FSHb conjugate

Chrusciel Marcin , Stelmaszewska Joanna , Doroszko Milena , Ponikwicka-Tyszko Donata , Toppari Jorma , Wolczynski Slawomir , Ziecik Adam , Huhtaniemi Ilpo , Rahman Nafis

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...

ea0073oc15.2 | Oral Communications 15: Late Breaking | ECE2021

Screening for mutations in isolated central hypothyroidism reveals a novel mutation in insulin receptor substrate 4 (IRS4)

Patyra Konrad , Kristiina Makkonen , Maria Haanpää , Karppinen Sinikka , Viikari Liisa , Jorma Toppari , Mary Pat Reeve , Kero Jukka

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...

ea0049oc4.2 | Thyroid Disease 1 | ECE2017

Inducible thyrocyte-specific Gs alpha-deficient mice as a novel model for hypothyroidism

Patyra Konrad , Jaeschke Holger , Undeutsch Henriette , Lof Christoffer , Ruohonen Suvi , Jannari Meeri , Chen Min , Weinstein Lee S. , Paschke Ralf , Toppari Jorma , Kero Jukka

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...

ea0049oc7.1 | Cardiovascular endocrinology (1) | ECE2017

Estrogens enhance gonadectomy-induced adrenocortical tumor progression in mice

Chrusciel Marcin , Doroszko Milena , Jakobi Meike , Brouze Michal , Ponikwicka-Tyszko Donata , Bernaczyk Piotr , Anisimowicz Slawomir , Wolczynski Slawomir , Toppari Jorma , Huhtaniemi Ilpo , Rahman Nafis

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...

ea0049gp118 | Endocrine Tumours | ECE2017

Luteinizing hormone receptor mediated GATA4 induction promotes adrenocortical tumorigenesis in gonadectomized mice

Doroszko Milena , Chrusciel Marcin , Stelmaszewska Joanna , Slezak Tomasz , Rivero-Muller Adolfo , Padzik Artur , Anisimowicz Slawomir , Wolczynski Slawomir , Huhtaniemi Ilpo , Toppari Jorma , Rahman Nafis

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...