Endocrine Abstracts

Fibrous dysplasia (FD) is a focal bone lesion composed of immature mesenchymal osteoblastic precursor cells which may occur at one site (monostotic) or multiple sites (polyostotic) in individual patients. Polyostotic FD may also be associated with other manifestations, including hyperpigmented (café-au-lait) skin lesions, gonadotropin-independent sexual precocity, and/or other endocrine and nonendocrine manifestations, and these constellation of features are known as the ...

Background: In addition to its normal spectrum of metabolic effects, insulin has been identified as a growth factor capable of promoting mitogenic activities. Thus, hyperinsulinemia, a consequence of insulin resistance, is regarded as a potential risk factor for the development of cancer in patients with diabetes. However, the mechanism of action of insulin in prostate cancer has not yet been completely elucidated. The aim of this study was to investigate whether insulin can d...

Background: IGF1R targeting emerged in recent years as a promising therapeutic approach in prostate cancer (PCa). The insulin receptor (IR) shares high structure homology with the IGF1R and activates similar signaling cascades. In recent studies we have shown that insulin’s mitogenic activities in PCa cells are mediated via the IR. Given the central role of IR in regulation of metabolism, most anti-IGF1R therapeutic strategies were designed to specifically inhibit IGF1R, ...

The ovarian enzyme 20alpha-hydroxy steroid dehydrogenase (20HSD) plays a central role in the termination of pregnancy in rodents. The enzyme which is expressed mainly in the corpus luteum, catalyzes the reduction of progesterone to 20alpha hydropregn-4en-3-one which is biologically inactive and cannot maintain pregnancy. During pregnancy ovarian 20HSD expression is inhibited, activity peaked in the CL of pregnancy about 24 hrs before parturition at the same time that progester...

Background and aims: Obesity is associated with dyslipidemia through insulin resistance and adipokines secretion, and weight loss can improve obese patients’ lipid profile. Here we aimed to assess whether non interventional weight changes are associated with alterations in the lipid profile, particularly the triglycerides (TG) to high density lipoprotein (HDL) cholesterol ratio (TG/HDL) which is an emerging marker for insulin resistance, the metabolic syndrome and an elev...

20alpha-hydroxysteroid dehydrogenase (20αHSD) has been initially characterized as a progesterone metabolizing enzyme of the ovary mandatory for the final reduction of progesterone blood levels before parturition. As the exact zonal distribution and regulation of adrenal 20αHSD has not been defined, adrenal 20αHSD expression and activity was determined by western blotting, immunohistochemistry and enzymatic assays in wild type BALB/c mice of both genders at diffe...

Gsα is a ubiquitously expressed G protein α-subunit that couples receptors to adenylyl cyclase and cAMP generation. In patients with Albright hereditary osteodystrophy (AHO), heterozygous Gsα mutations only lead to obesity when present on the maternal allele. Similarly, mice with heterozygous germline Gsα mutations on the maternal allele develop severe obesity and insulin resistance with reduced energy expenditure relative t...

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...

Background: Multiple studies have shown that approximately 50-70% of patients with MEN1 die of causes directly related to MEN1 particularly gastroenteropancreatic (GEP) neuroendocrine tumors (NETs). While non-functional GEP-NETs are the most common in the general population, gastrinomas (40%) are the most common functional GEP-NETs in patients with MEN1. c-Met is a proto-oncogene that encodes for c-MET, a tyrosine kinase receptor which promotes tumor cell motility, proliferati...

Background: The presence of a genotype-phenotype correlation in patients with MEN1 remains controversial with conflicting data from different centers. Furthermore, about 10-30% patients have genotype-negative (GN)-MEN1. Here, we evaluate the presence of genotype-phenotype correlation in our cohort of comprehensively phenotyped patients with MEN1. In addition, we compare the phenotype of GN-MEN1 and genotype-positive (GP)-MEN1 patients and investigate somatic mosaicism as a cau...