Endocrine Abstracts

Equine chorionic gonadotrophin (eCG) is not only essential for the maintenance of early equine pregnancy but is also used therapeutically for synchronisation of farm and laboratory animals. Currently it is extracted from serum of farmed pregnant mares. We have recently reported that under normoxic conditions, BMP4 treatment of equine trophoblast resulted in a dose, and developmental stage-dependent increase in total number of differentiated binucleate cells that secrete eCG. O...

Key genetic contributors are recognised to underlie the phenotype of central precocious puberty (CPP), including the imprinted genes Makorin ring finger protein 3 (MKRN3) and Delta-like homolog 1 (DLK1), alongside Kisspeptin-1 (KISS1) and (KISSR1). These genes have implicated mis-regulation of transcriptional control of the kisspeptin and gonadotropin-releasing hormone (GnRH) neuroendocrine systems in onset of CPP. However, many familial cases of CPP remain without clear a gen...

Mutations in each of the 4 subunits of succinate dehydrogenase (SDH) – SDHA, B, C and D predispose to development of phaeochromocytomas and paragangliomas. Loss of SDH function leads to accumulation of succinate which acts as an oncometabolite to drive tumourigenesis. However, mutations in SDHB have an increased likelihood of causing metastatic disease, compared to mutations in the other SDH subunits. The reasons behind this increased risk remai...

Familial glucocorticoid deficiency (FGD) is characterised by isolated glucocorticoid deficiency with retention of normal mineralocorticoid production. FGD causing mutations in the MC2R accessory protein, MRAP, often occur at the canonical donor splice-site of intron 3, presumed to result in skipping of the first coding exon with unknown consequences at the protein level. DNA from three patients (0 - 6 months) with high ACTH and/or low cortisol levels underwent whole e...

Equine Chorionic Gonadotrophin (eCG) is a heterodimeric glycoprotein produced by terminally differentiated, bi/multi-nucleate trophoblast cells in the placenta of horses and humans. It is responsible for the maintenance of early pregnancy via rescue of the corpus luteum and subsequently promotion of progesterone production. The beta subunit of eCG is expressed at levels ten-fold lower than that of the alpha subunit and confers the glycoproteins specificity to the placenta. Ver...

Placental chorionic gonadotrophin (CG) hormone secretion, critical for maintenance of early pregnancy, is dependent on differentiation of specialised CG-secreting binucleate trophoblast (horse) and syncytiotrophoblast (human). The most abundant genes expressed by binucleate cells are the α and β subunits of equine CG. We recently showed the transcription factor glial cells missing 1 (GCM1) is rapidly induced during differentiation of binucleate trophoblast and mRNA e...

Loss of function of succinate dehydrogenase (SDH), caused by mutations in each of the 4 subunits – SDHA/B/C and D – is associated with development of phaeochromocytomas and paragangliomas (PPGLs). The mutations lead to loss of enzymatic activity and subsequent accumulation of the oncometabolite succinate, a driver of tumourigenesis. It is well established but poorly understood why mutations in SDHB are associated with more aggressi...

Primary adrenal insufficiency in children can be due to mutations in >20 genes, most commonly CYP21A2, giving rise to 21-hydroxylase deficiency. Phenotypically these disorders overlap and present with conditions ranging from isolated (or familial) glucocorticoid deficiency (FGD) to syndromic disorders involving multiple tissues. Distinguishing between them can be problematic, especially where biochemical testing is not possible or not undertaken. Over the last 30 ...

Background: Primary adrenal insufficiency (PAI) can be associated with significant morbidity in children of all ages, the most common cause being Congenital Adrenal Hyperplasia (CAH). Several other rare inherited causes of PAI have been identified over the years which lack diagnostic phenotypic or biochemical signs, leaving genetic testing as the only approach to make a definitive diagnosis. Our cohort involves >440 patients who presented with features of PAI – hypogl...

Primary adrenal insufficiency (PAI) in children is usually congenital with more than 25 causal genes leading to overlapping phenotypes. A genetic diagnosis is helpful to guide management and genetic counselling but can be challenging in resource limited settings where facilities for antibodies and genetic testing may be unavailable. Studies from Africa are rare but, in Sudan, the most common genetic aetiologies for PAI are congenital adrenal hyperplasia (CAH; mostly CYP21A...