Endocrine Abstracts

Aberrant development of the pituitary gland can result in the clinical manifestation of hypopituitarism. The Wnt/β-catenin pathway has been shown to be involved in normal organogenesis, terminal differentiation and the aetiology of pituitary tumours. However, the specific developmental roles during hypothalamic–pituitary development of some of the Wnt/β-catenin effectors, such as Tcf3, have been hampered due to the early lethality of null embryos for th...

Introduction: Hypogonadotrophic hypogonadism (HH) is a genetically heterogeneous disorder. A number of genes have been implicated in its pathogenesis but, to date, in most cases, the cause remains genetically unknown.Case: A 14-year old male with delayed puberty (G1P2A3, testes two males) and family history of HH was diagnosed with HH following anterior pituitary assessment and an overnight gonadotrophin profile. His baseline gonadotrophins were low (LH,...

Introduction: KAL1 is essential for GnRH neuronal migration and olfactory bulb development, and mutations within this gene have been implicated in 5% of Kallmann syndrome (KS) cases, a disorder characterized by the association of hypogonadotrophic hypogonadism with anosmia. It is the only identified X-linked form of the disorder and as a result only KS males had been screened for mutations until recently, when females exhibiting KS phenotypes were screened and subsequen...

The key mitotic regulator pituitary tumor transforming gene (PTTG) is expressed at low levels in fetal brain compared with adult, and modulates the proliferation of human embryonic neuronal N-Tera2 (NT2) cells. We examined the function and expression of PTTG’s interacting partner separase, along with Rad21, the functional component of cohesin, which is cleaved by separase following interaction with PTTG. In contrast to PTTG, the cleaved forms of separase and Rad21 were hi...

The pituitary gland, is a small midline organ situated at the base of the brain, that acts as a master regulator of multiple physiological functions: such as growth, puberty, metabolism, stress response, reproduction and lactation. The pituitary gland is composed of three lobes: the anterior and intermediate, which form the anterior pituitary (AP and contains hormone producing cells), and the posterior lobe which constitutes the posterior pituitary (PP contains axonal inputs)....

Introduction: Loss-of-function mutations in PROK2 and PROKR2 in humans have been associated with Kallmann syndrome (KS), characterised by the combination of hypogonadotrophic hypogonadism with anosmia, suggesting that both are critical for GnRH neuronal development.Objective: KS has overlapping phenotypes and genotypes through FGF8 and FGFR1 with congenital hypopituitarism including septo-optic dysplasia (SOD) and thus we aime...

Loss-of-function mutations in FGF8 in humans have been associated with Kallmann syndrome (KS), which is characterised by the combination of hypogonadotrophic hypogonadism with anosmia, suggesting that FGF8 is critical for GnRH neuronal development. Interestingly, hypomorphic Fgf8 mutant mice demonstrate poor telencephalic development with deletions of midbrain tissue, absence of olfactory bulbs and optic chiasm, and holoprosencephaly (HPE) with an abnormal corpus...