Endocrine Abstracts

Familial hypocalciuric hypercalcaemia (FHH) is an autosomal dominant disorder characterised by hypercalcaemia and inappropriately low renal calcium excretion. FHH can be classified into three types: FHH1, caused by calcium-sensing receptor (CaSR) loss-of-function mutations, accounting for >65% of cases; FHH2, due to loss-of-function mutations of the G-protein α11 subunit (Gα11); and FHH3, resulting from loss-of-function mutations in the adap...

G-protein coupled receptors (GPCR) mediate the effects of multiple hormones, and consequently are fundamental for endocrine functions including glucose homeostasis, thyroid function, fertility, control of urine output, and bone remodelling. Mutations in genes encoding GPCRs result in endocrine disorders, and studies of these mutations has improved understanding of GPCR signalling and trafficking pathways, and could facilitate novel therapies. The calcium-sensing receptor (CaSR...

G-protein coupled receptors (GPCR) mediate the effects of multiple hormones, and consequently are fundamental for endocrine functions including glucose homeostasis, thyroid function, fertility, control of urine output, and bone remodelling. Mutations in genes encoding GPCRs result in endocrine disorders, and studies of these mutations has improved understanding of GPCR signalling and trafficking pathways, and could facilitate novel therapies. The calcium-sensing receptor (CaSR...

Adrenocortical adenomas are among the most commonly identified human neoplasias, with a prevalence of 2-3% in the population. In some cases they are associated with autonomous cortisol excess that leads to increased morbidity and mortality. Altered cAMP/protein kinase A (PKA) signalling is common in sporadic cortisol-producing adenomas (CPA), mostly caused by somatic mutations in the genes coding for the catalytic subunit α of PKA (PRKACA) or the stimulatory G-pr...

Pituitary luteinizing hormone (LH) and placental human choriogonadotropin (hCG) are two heterodimeric glycoprotein hormones regulating reproduction. They bind the same receptor (LHCGR) expressed in gonadal cells, activating hormone-specific G protein- and β-arrestins-dependent signaling cascades, before LHCGR internalization. LH induces preferential proliferative signals, while hCG activates mainly the steroidogenic pathway, reflecting their physiological roles. In this s...

Introduction: Most serum cortisol (SeC) is linked to cortisol binding globulin and albumin. When the synthesis of proteins is reduced or increased, SeC does not reflect the actual free cortisol (FC) (active fraction). Methods for FC analysis are very laborious and expensive, which makes difficult to use them as a routine laboratory tests. Salivary cortisol (SaC) mirrors the FC in serum, being its measurement easier and cheaper. The determination of SaC, instead of tot...

Background: Follicle-stimulating hormone receptor (FSHR) and G protein-coupled estrogen receptor (GPER) are expressed on the surface of granulosa cells, where they form heteromeric complexes, shifting FSH-induced signals to survival pathways and determining the follicular fate.Objectives: We evaluated whether GPER can interact with the luteinizing hormone (LH)/choriogonadotropin (hCG) receptor (LHCGR) and modulate the LH/hCG/dependent signalling pathways...

G-protein subunit α-11 (Gα11), which is encoded by GNA11, plays a major role in calcium homeostasis by regulating parathyroid hormone (PTH) secretion, and germline loss-of-function mutations cause familial hypocalciuric hypercalcaemia type 2 (FHH2). Since Gα11 is ubiquitously expressed, we investigated whether FHH2 is associated with additional non-calcitropic phenotypes by analysing mice harbouring a homozygous germline deletion o...

Introduction: Despite being on adequate amounts of levothyroxine (>1.6 μg/kg) some patients still exhibit biochemical evidence of inadequate replacement (serum TSH >4.2 mIU/l±free-thyroxine (FT4) <12 pmol/l). We report the use of a 5-day absorption test for assessing levothyroxine absorption in such a patient.Case: A 35-year-old female with hypothyroidism since 2007 had a serum TSH ranging from 4.48 to 54.9 mIU/l and FT<s...

The calcium-sensing-receptor (CaSR) is a G-protein-coupled receptor that plays a fundamental role in extracellular calcium homeostasis, but is also implicated in non-calcitropic disorders including colon cancer and asthma. In addition, CaSR is highly expressed in pancreatic islets where it has a role in insulin secretion. Patients with gain-of-function CaSR mutations, and mice (referred to as Nuf) with a gain-of-function CaSR mutation (Leu723Gln), develop autosomal dominant hy...