Endocrine Abstracts

Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor highly resistant to chemo-and radiotherapy. Since several reports showed that cAMP has an antiproliferative effect on different types of solid tumors both in vitro and in vivo, we evaluated the potential anti-neoplastic activity of cAMP analogues (8-Cl-cAMP and the equimolar combination of 8-PIP-cAMP and 8-HA-cAMP) in two MTC cell lines (TT and MZ-CRC-1 that harbor C634W and M918T RET mutations, respecti...

Primary Ovarian Insufficiency (POI) is an ovarian defect characterized by the premature depletion of ovarian follicles before 40 years and represents one major cause of female infertility. POI is a heterogeneous disease but, despite its idiopathic origin in most of patients, there is a strong genetic evidence, in particular for X chromosome-linked defects. BMP15 gene maps to Xp11.2 within a Turner locus critical for ovarian function and mutations in this gene have been found i...

Introduction: MEN-1 is a rare autosomal dominant familial cancer syndrome characterized by involvement of parathyroid glands, enteropancreatic endocrine tissues and anterior pituitary gland. This disease is linked to germline mutations in the MEN1 gene (more than 460 described), whose identification allows the familial genetic counselling. Here we describe a novel germinal mutation in exon 10 of the MEN1 gene identified in an Italian family.Case Report: ...

Introduction: Epidemiological data indicate that children born prematurely have a risk 3–5 fold higher of congenital hypothyroidism (CH). In addition premature infants born small for gestational age (SGA) have a risk of 12% higher to develop IC compared to prematures with appropriate development (AGA). The mechanisms that justify the increased risk of IC are still unknown. Some studies report a pattern of aberrant methylation associated with prematurity, intrauterine feta...

BMP15 is a TGFβ-like oocyte-derived growth factor involved in ovarian folliculogenesis as a critical regulator of many granulosa cell processes. BMP15 is synthesized as a pro-protein which dimerizes and then is processed in the bioactive mature domain and a large prodomain. The proregion has an important role in the BMP15 processing by driving the dimerization and secretion of the active mature dimers. Since several mutations in the BMP15 gene have been found with differe...

Primary ovarian insufficiency (POI) is a critical fertility defect characterized by a progressive and silent impairment of the follicular reserve. POI aetiology is heterogeneous and largely unknown, but a maternal inheritance often characterizes idiopathic forms. Therefore, we hypothesized a possible involvement of a mitochondrial defect in the pathogenesis of this disease since mitochondrial biogenesis and bioenergetics play an essential role in ovarian folliculogenesis. Our ...

Introduction: Idiopathic central hypogonadism (ICH) is a rare and heterogeneous disease due to defects of GnRH secretion or action. ICH could be associated or not with hypo-anosmia respectively identifying the Kallmann’s syndrome (KS) or the normosmic ICH (nICH). Even though 14 disease genes have been identified, in 70% of patients no genetic cause could be identified, suggesting additional regulatory genes and still unknown mechanisms. Thus, with the aim to identify new ...

Thyroid cancer is the most common endocrine malignancy characterized by a good prognosis. However, the subgroup of poorly differentiated thyroid carcinomas (PDTCs) includes neoplasia highly aggressive and scarcely responsive to currently available therapies.Site-selective cAMP analogs are able to inhibit the growth of poorly differentiated solid tumors and may represent valuable candidates for the therapy of PDTCs.We evaluated the ...

Spontaneous puberty occurs in a subset of Turner syndrome (TS) patients with significant 45,X/46,XX mosaicism. This observation leads to the belief that haploinsufficiency of still unidentified genes on the X chromosome is the cause of the accelerated follicle atresia in TS. Examination of particular X chromosome rearrangements/deletions led to the identification of 2 Xq and 1 Xp loci associated to the ovarian defect in TS. The availability of new generation genetic and cytoge...

In thyroid cells TSH/cAMP stimulation is associated with proliferation and differentiation. The principal effector of cAMP is the protein kinase A (PKA) and events downstream PKA activation, signaling specificity and expression of PKA isoforms are largely unexplored. PKA is composed of two regulatory and two catalytic subunits. Two major isoforms of PKA (I and II) are determined by their specific regulatory subunits (RIα, RIβ, RIIα and RIIβ). A recent gene ...