Endocrine Abstracts

The autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) syndrome is an autosomal recessive disorder characterized by immune deficiency and the autoimmune destruction of endocrine organs such as the parathyroids, adrenal cortex and ovaries. APECED is caused by biallelic germline mutations of the autoimmune regulator (AIRE) gene on chromosome 21q22.3, which is expressed in thymic medullary epithelial cells and plays a key role ...

Hypoparathyroidism may occur as: a hereditary syndromic disorder (e.g. Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED), Hypoparathyroidism Sensorineural Deafness and Renal Disease (HDR), Autosomal Dominant Hypoparathyroidism type 1 (ADH1), or ADH type 2 (ADH2), which are due to mutations of autoimmune regulator (AIRE), GATA binding protein 3 (GATA3), calcium-sensing receptor (CASR) and G-protein sub...

Loss- and gain-of-function mutations of the calcium-sensing receptor (CaSR) cause familial hypocalciuric hypercalcaemia (FHH) and autosomal dominant hypocalcaemia (ADH), respectively. The CaSR is a homodimeric receptor that has a 612 amino acid extracellular domain (ECD), which binds extracellular calcium (Ca2+e) and mediates dimer interactions upon ligand binding. The ECD consists of lobes 1 and 2, and a cysteine-rich domain (CRD). To elucidate the struc...

Heterotrimeric G-proteins are important molecular switches that transduce extracellular ligand-binding at G-protein-coupled receptors (GPCRs) to intracellular signals. G-protein alpha-subunits (Gα) have two domains, a helical and GTPase domain, which provide structural stability and mediate GTPase activity, respectively. Gain-of-function Gα mutations cause endocrine conditions including McCune-Albright Syndrome, due to Gαs mutations, and a...

The autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) syndrome is an autosomal recessive disorder characterized by immune deficiency and the autoimmune destruction of endocrine organs such as the parathyroids, adrenal cortex and ovaries. APECED is caused by biallelic germline mutations of the autoimmune regulator (AIRE) gene on chromosome 21q22.3, which is expressed in thymic medullary epithelial cells and plays a key role ...

Hypoparathyroidism may occur as: a hereditary syndromic disorder (e.g. Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED), Hypoparathyroidism Sensorineural Deafness and Renal Disease (HDR), Autosomal Dominant Hypoparathyroidism type 1 (ADH1), or ADH type 2 (ADH2), which are due to mutations of autoimmune regulator (AIRE), GATA binding protein 3 (GATA3), calcium-sensing receptor (CASR) and G-protein sub...

Increased mammary metabolism is critical for initiating lactation during postpartum days 1-4. We utilised clinical and cellular approaches to investigate whether thyroid hormones, which promote lactation in rodents, are involved in initiating human lactation and regulating mammary metabolism. We recruited n=30 pregnant women following informed consent and measured serum thyroid hormones (free T4 and TSH) at 36 weeks’ gestation and on postpartum day 4. Free T4 inc...

Increased mammary metabolism after child-birth supports the synthesis of milk components and is critical for initiating lactation during postpartum days 1-4. We utilised clinical and cellular approaches to investigate whether growth hormone (GH), which is reported to increase milk yield in breastfeeding women, may play a role in initiating lactation and promoting mammary metabolism. We recruited n=30 pregnant women (age range 24-41 years) following informed consent an...

The onset of lactation during post-partum days 1-4 is hormonally-regulated and critical for successful breastfeeding. Insulin represents a key lactogenic hormone as evidenced by women with type 1 diabetes who have delayed lactation onset. However, the role of insulin in lactation and its influence on mammary cells are unclear. We utilised clinical and cellular approaches to investigate this, and recruited n=12 women following informed consent and measured serum insuli...

The onset of lactation occurs during postpartum days 1-4 and is associated with altered mammary metabolism leading to increased milk component synthesis. We hypothesised that increases in metabolic hormones or cytokines after childbirth may support these processes. To investigate this, we recruited n=12 pregnant women following informed consent and measured: prolactin; thyroid-stimulating hormone; insulin; cortisol; insulin-like growth factor-1; and interleukin-6 (IL-...