Endocrine Abstracts

Introduction: Prostate cancer is the most prevalent malignancy affecting Western males. Initially an androgen-dependent disease, androgens bind to the androgen receptor and drive expression of genes that promote proliferation and evasion of apoptosis. Although advanced disease involves reduced androgen dependence, androgen receptor signalling remains a key driver of growth. Androgen deprivation therapy (ADT) is first line, but resistance inevitably develops. A...

Endometrial cancer is the most common gynaeological malignancy in the developed world: lifetime exposure to oestrogen is a key risk factor. Oestrogen action is mediated by ligand activated receptors encoded by the ESR1 (ERα) and ESR2 (ERß) genes: ERα plays a key role in regulating endometrial cell proliferation. ERß5, is a truncated variant isoform of ERß formed by alternative splicing of ESR2 that contains a DNA binding doma...

During the establishment of pregnancy, the endometrium undergoes dynamic remodelling in order to establish a ‘receptive’ microenvironment. Decidualisation, a key part of this process, is characterised by differentiation of endometrial stromal fibroblasts which secrete factors that regulate implantation and placental development. Recent studies in our laboratory have revealed that decidualisation results in altered expression of enzymes that regulate biosynthesis and ...

Background: Visceral fat is a key factor underlying type 2 diabetes. The amount and distribution of body fat is strongly influenced by sex steroids. Androgen receptors (ARs) are present in adipose tissue and are abundant in the detrimental visceral bed. Here, we sought to determine the contribution of the AR in adipose tissue to the pathophysiology of visceral obesity and type 2 diabetes.Methods: Male fat-specific AR-knockout (fARKO) mice (12 weeks; n...

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...

The human endometrium is a complex multicellular tissue the prime function of which is to provide a receptive environment during a fertile cycle. The tissue responds to steroid hormones exhibiting dynamic cyclical regeneration, angiogenesis, differentiation (decidualisation) and inflammation. In the absence of an embryo the inner surface is shed and repaired without scarring (menstruation). The endometrium exhitbits spatial and temporal expression of androgen receptors (AR) in...

Endometrial cancer (EC) is the most common gynaecological malignancy. Obesity is a major risk factor for EC and is associated with elevated cholesterol. 27-Hydroxycholesterol (27HC) is a cholesterol metabolite that functions as an endogenous agonist for Liver X Receptor (LXR) and a selective estrogen receptor modulator (SERM). Exposure to estrogenic ligands increases risk of developing EC however the impact of 27HC on EC is unknown.Samples of stage 1 EC ...

Heavy menstrual bleeding (HMB) is common and debilitating but it remains a taboo subject. Hence its cause remains undefined, resulting in non-specific hormone therapies with intolerable side effects.Over 70 years ago it was proposed that progesterone withdrawal caused intense vasoconstriction and a transient endometrial hypoxia that resulted in menstruation. Subsequent research confirmed that inflammation initiated menses and disputed the role of hypoxia...

Heavy menstrual bleeding (HMB) is common and debilitating but it remains a taboo subject. Hence its cause remains undefined, resulting in non-specific hormone therapies with intolerable side effects.Over 70 years ago it was proposed that progesterone withdrawal caused intense vasoconstriction and a transient endometrial hypoxia that resulted in menstruation. Subsequent research confirmed that inflammation initiated menses and disputed the role of hypoxia...

The endometrium is a complex tissue with luminal and glandular epithelial cell layers supported on a multicellular stromal compartment; in women the inner (luminal) portion of the tissue breaks down and is shed during menstruation. The endometrium is exquisitely sensitive to the actions of sex steroids (oestrogens, progestogens and androgens) produced in ovarian and other extra gonadal tissues and delivered via blood vessels that rapidly develop and mature within the tissue (e...