Endocrine Abstracts

Wolffian duct (WD) development is believed to be testosterone dependent. However, patients with complete androgen insensitivity syndrome (CAIS) and a causative mutation in the androgen receptor (AR) still develop WDs. Exceptions to this observation are those patients with severe N-terminal mutations. We investigated the role of the AR in WD development in these patients.AR expression in genital skin fibroblasts (GSF) from eleven patients with CAIS was studied by Western hy...

Sex differentiation is the development of the internal and external genitalia following gonad determination. Genital ridge formation is regulated by WT1, SF1 and LHX9 whereas SRY is a major player in testis determination. Quite how SRY functions as a transcription factor is still unknown twelve years after the (i)SRY(/i) gene was cloned. How testis determination is regulated is incomplete, as the cause of sex reversal is unknown in the majority of patients with XY gonadal dysg...

The Androgen Receptor (AR) is a ligand dependent transcription factor that regulates the development and maintenance of the male reproductive system. Previous studies in AIS have demonstrated ligand binding domain mutations resulting in decreased trans-activation activity through reduced N-terminal/C-terminal interaction of the AR, despite unaltered ligand binding ability.We have introduced mutations in the hinge region of the Androgen Receptor (AR) and assessed the effect...

Hormonal activation of the androgen receptor plays a critical role in male fetal sex differentiation.Current hypotheses concerning estrogen/androgen balance and the role of estrogenic environmental contaminants have led us to investigate the capacity for androgenic/antiandrogenic activity in such chemicals. We have previously developed a sensitive in vitro assay using a telomerase-immortalised human cell line capable of detecting putative endocrine disrupting activi...

Complete androgen insensitivity syndrome (CAIS), is generally caused by a mutation in the androgen receptor (AR) gene. In sequencing genomic DNA from patients with CAIS, we identified 7 novel mutations in the AR. Their effects on AR function are speculated in relation to AR functional domains and crystal structure. Local Ethical Committee approval was obtained for the use of patient samples.Exon 1 mutations, Q86X and Y480X, are located in the transactiv...

Antipsychotic induced hyperprolactinaemia, mediated by blockade of dopamine D2 receptors, is much more common than prolactinoma in patients receiving antipsychotic medication. We present two cases of the latter.Case 1: A 47-year-old gentleman with depression treated with amitriptyline, fluoxetine and risperidone presented with headaches and a left sided visual field defect. Pituitary MRI showed a 2 cm macroadenoma abutting the optic chiasm. Prolactin was...

Background: The published data on the natural history of (presumed) non-functioning pituitary microadenomas (micro-NFAs) is possibly compromised by small sample sizes, short follow-up and inclusion of cases with other pathologies in the analyses.Objective: To clarify the long-term outcomes of micro-NFAs in a large cohort of patients.Methods: We conducted a multi-centre, retrospective, cohort study involving 22 UK endocrine departme...