Endocrine Abstracts

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...

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...

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-...

Lactation promotes infant development and confers long-term health benefits to mothers and infants. However, the endocrine and paracrine mechanisms mediating milk synthesis remain to be fully elucidated. Hormones such as prolactin and progesterone trigger the onset of lactation, whereas local mammary factors are considered to play a greater role in the maintenance of milk synthesis. We hypothesised that mammary epithelial cytokines are required for established lactation, and u...

The calcium-sensing receptor (CaSR) is a G-protein coupled receptor that predominantly signals via Gαq/11-mediated pathways to regulate extracellular calcium (Ca2+e) homeostasis. Germline Gα11 inactivating and activating mutations cause familial hypocalciuric hypercalcaemia type-2 (FHH2) and autosomal dominant hypocalcaemia type-2 (ADH2), respectively. To date, four FHH2 and six ADH2 mutations have been reported. To identif...

Familial hypocalciuric hypercalcaemia (FHH) is an inherited disorder of calcium homeostasis, which is caused by germline loss-of-function mutations of the calcium-sensing receptor (CaSR) in ˜70% of cases. We report a 22 year old woman who was referred with asymptomatic hypercalcaemia. Biochemical investigations revealed hypercalcaemia on 3 of 4 occasions with adjusted serum calcium ranging from 2.59–2.80 mmol/l (normal range 2.20–2.60 mmol/l). Parathyroid hormon...