Searchable abstracts of presentations at key conferences in endocrinology

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...

ea0041gp117 | Endocrine Tumours | ECE2016

FSH supplementation increases the growth of PC-3 human prostate cancer cell xenograft in gonadotropin-suppressed nude mice

Oduwole Olayiwola , Poliandri Ariel , Rawson Phil , Rahman Nafis , Koechling Wolfgang , Huhtaniemi Ilpo

Gonadotropin-releasing hormone (GnRH) analogues are now the standard hormonal treatment for prostate cancer. A fundamental difference between GnRH agonist and antagonist treatment is the permanent suppression of both gonadotropins (LH and FSH) by antagonist, while a rebound in FSH is associated with agonist treatment. The benefits of antagonist include the immediate onset of action and profound long-term suppression of FSH, suggested to be an independent growth factor in prost...

ea0037gp.30.05 | Endocrine tumours and neoplasia – General | ECE2015

Targeted destruction of FSHR-positive cells by lytic peptide Phor21 conjugated with FSHβ subunit in vitro

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

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 ...

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...

ea0035p518 | Endocrine tumours and neoplasia | ECE2014

Molecular mechanisms of unexpected promoting effects of progesterone and mifepristone on granulosa cell tumorigenesis

Ponikwicka-Tyszko Donata , Chrusciel Marcin , Stelmaszewska Joanna , Bernaczyk Piotr , Li Xiangdong , Huhtaniemi Ilpo , Wolczynski Slawomir , Rahman Nafis A

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...

ea0022h1.4 | Oral Communications Highlights 1 | ECE2010

Physiological rescue by functional complementation of mutated LH receptors in transgenic mice

Rivero-Muller Adolfo , Chou Yen-Yin , Lajic Svetlana , Hanyaloglu Aylin , Jonas Kim , Rahman Nafis , Ji Tae , Huhtaniemi Ilpo

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...

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...

ea0086op2.4 | Adrenal and Cardiovascular | SFEBES2022

Delta-like non-canonical notch ligand 1 (DLK1)-expressing adrenocortical progenitor cells: role in adrenal turnover, remodeling and tumorigenesis in mice

Mariniello Katia , Pittaway James , Hadjidemetriou Irene , Borges Kleiton , Doroszko Milena , Doghman Mabrouka , Lalli Enzo , Rahman Nafis , Breault David , Rognoni Emanuel , Guasti Leonardo

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...

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...