Endocrine Abstracts

The oestrogen-receptor related orphan nuclear receptors (ERR) share significant sequence homology with oestrogen receptors (ER) alpha and beta but are unable to bind oestradiol. They are reported to constitutively regulate gene expression by binding to the ER response elements (ERE) or SF1 binding sites (SFRE) in gene promoters. However recent evidence from transgenic animal models point towards a role of these orphan nuclear receptors as regulators of energy-producing metabol...

Oestrogen receptor (ER) activity has a wide spectrum of functions in the human body, including the development, growth and maintenance of the reproductive system. There are two ER subtypes, ERα and ERβ. The latter exists as multiple splice variants (ERβ1, ERβ2 and ERβ5) some of which lack a steroid ligand-binding domain. ERs act as steroid-ligand activated transcription factors. Epidermal growth factor (EGF) acting via the MAP kinase pathway has been s...

Steroid receptors are members of a family of ligand-activated transcription factors that mediate tissue responses to a variety of endocrine stimuli. Using the human endometrium as a paradigm of a steroid responsive tissue, we aimed to characterise the expression and function of the oestrogen-receptor related orphan nuclear receptors (ERR) alpha and beta. ERRs share significant sequence homology with oestrogen receptors (ER) alpha and beta but are unable to bind oestradiol. The...

From human epidemiological and related studies, there is strong (indirect) evidence that common male reproductive disorders that manifest at birth (cryptorchidism, hypospadias) or in adulthood (low sperm count, low testosterone, primary hypogonadism) may have a common origin in foetal life due to impaired androgen (testosterone) production or action; the so-called testicular dysgenesis syndrome (TDS) hypothesis. Whilst the foetal origin of cryptorchidism and hypospadias is sel...

Background: 5-Cytosine methylation of DNA is a means of encoding epigenetic information. In the testis, the generation of de novo methylation is conducted by the enzymes DNMT3a and 3b and the co-enzyme DNMT3L. Epigenetic marks made to the DNA of germ cells are important as a potential means of trans-generational carriage of environmental information. In fetal life, germ cell demethylation and remethylation are important physiological events and these overlap with key ...

Fetal events can affect adult testosterone levels but how this occurs is unknown, as adult Leydig cells (ALC) do not differentiate until puberty. Qin et al. 2008 (PLos ONE) identified that chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) is essential postnatally for ALC development. We hypothesized that: i) COUP-TFII+ non-Leydig interstitial cells are progenitors for ALC and are present in the fetal testis, ii) these ‘pr...

Background: Endocrine disruption in the human fetal testis by environmental agents has been proposed as a possible cause of testicular dysgenesis syndrome (TDS) comprising male reproductive disorders such as testicular germ cell tumours (TGCT), cryptorchidism, hypospadias and low sperm counts. Exposure of fetal rats to the widely used plasticizer di(n-butyl) phthalate (DBP) results in a TDS-like syndrome due to a reduction in testosterone production. Whether such effects also ...