Endocrine Abstracts

G protein-coupled receptors (GPCRs) are one of the largest families of the mammalian genome, mediating the effects of approximately 40% of prescribed drugs. Until recently, accepted dogma stated that GPCRs exist as monomers, however, it is becoming evident that GPCRs can form higher order dimer/oligomer complexes which provide important mechanisms for the diversification of receptor function. The LHCGR is a class A family GPCR, primarily coupling to the Gαs pat...

GnRH acts via G-protein coupled receptors to stimulate synthesis and secretion of luteinizing hormone and follicle-stimulating hormone. GnRH activates phospholipase C, causing calcium mobilisation and influx, activation of protein kinase C and stimulation of mitogen-activated protein kinase cascades. GnRH is secreted in brief pulses with each pulse causing rapid and transient activation of extracellular signal regulated kinases (ERKs) (1), yet very little is known about what s...

Clomiphene is commonly first-line treatment for ovulation induction in women with PCOS. Clomiphene results in a rise in serum FSH concentration; its effect upon FSH glycosylation is less clear. Glycosyl components of serum gonadotrophins are important determinants of their bioactivity.We compared serum FSH glycosylation in blood samples taken from healthy women with regular ovulatory cycles (group A; n=8) and anovulatory women before (group B; ...

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 ...

Polycystic ovary syndrome is the commonest cause of anovulation. The mechanism of the aberrant follicle development that is associated with anovulation remains unclear. However, data from human studies and from animal models of PCOS suggest that excess androgen production, the biochemical hallmark of PCOS, has a role in disordered follicle development. The aim of this study was to examine the direct effect of androgens on isolated mouse preantral follicles in culture. Multilay...

The glycosyl components of serum gonadotrophins are important determinants of biological half life, receptor binding and bioactivity of these hormones. We have compared serum FSH glycosylation from healthy women with regular ovulatory cycles (group A; n=8) to those identified inpharmacological preparations gonadotrophins (group B merional and group C puregon). Blood samples were taken within 4 days of the onset of menstruation in the control group (group A). Pharmaceuti...

Prostaglandins are important mediators of reproductive function. However, comparative differences in functional prostanoid receptors during gestation and postpartum are not fully explored. The aim of this study was to compare the responsiveness to PGF2α, PGE2, and U46619 in the rat uterine horn at late gestation and postpartum. Rats were sacrificed at late gestation (n=5–6) and at postpartum (n=5–6). Uterine horns were opened longitudinally, cleare...

Background: Exposure to environmental radiation can cause stress and cumulative effect of such stress leads to DNA strand brake. Testicular function is particularly susceptible to radiation emitted by electromagnetic fields. Reports of declining male fertility have renewed interest in the role of environmental and occupational exposures in the aetiology of human infertility.Objectives: The aim of the present work was to investigate the effect of 10 GHz e...

In women with PCOS, raised serum LH concentration is associated with lower age and BMI; converse associations are identified in women with IR. Our initial analysis of women with PCOS showed a 20–30% overlap of women with both raised serum LH concentration and IR. To investigate further the relationship between LH and IR we analysed endocrine data from a group of women diagnosed with PCOS by Rotterdam criteria. Notes of 241 women identified as having PCOS were reviewed; me...

Background: Testosterone deficiency is common in obesity and in type 2 diabetes mellitus. It is hypothesised that the expanded adipose pool, which is the major source of aromatase in men, depletes testosterone levels by excess conversion to estradiol. Individuals with either the GG rs2470152 polymorphism in intron 1 or a high number of TTTA repeats in intron 4 of CYP19 are known to have greater aromatase activity with demonstrable effects upon plasma estradiol and osteoporosis...

The aim of por in-vitro studies was to examine the involvement of transcription factor NF-kB (p50/p50, p65/p65) and FSH in control of porcine ovarian granulosa cells functions and the possible role of dimers p50/p50, p65/p65 in mediating FSH actions on these cells. Monolayer of primary granulosa cells was transfected with plasmids encoding human p50 cDNA and p65 cDNA, and cultured with or without addition of FSH (0, 1, 10 or 100 ng/ml). The accumulation of proteins p50 and p65...

We have investigated cell proliferation and apoptosis in Cyp11b1 null (ko) mice. Reduced glucocorticoid (corticosterone) synthesis in ko mice is associated with increased progesterone and deoxycorticosterone and the development of adenomyosis. Numbers of putative uterine stem cells were assessed in wild type (wt) and ko at an age (10–12 months) when the onset of adenomyosis was considered imminent. Mice were infused with bromodeoxyuridine (BrdU) for seven days then killed...

Chorionic Gonadotrophin (CG) is secreted by both horse and human placenta and is critical to maintenance of early pregnancy. Production of CG is dependent on the differentiation of specialised CG-secreting cells, binucleate (horse) and syncytiotrophoblast (human). We recently showed the transcription factor Glial Cells Missing 1 (GCM1) is rapidly induced in vivo during differentiation of equine binucleate trophoblast. Studies in human syncytiotrophoblast have shown cAMP...

Kallmann syndrome is a treatable form of male infertility caused by a congenital defect in the secretion or action of gonadotropin releasing hormone (GnRH). It can permanently remit in around 10% of male cases. We report a patient with atypical Kallman’s syndrome who requires intermittent testosterone replacement to sustain activity of his gonadotrophic axis A 55 year old male presented with erectile dysfunction and decreased libido. He reported normal puberty, with no hi...

Background: Male hypogonadism is commonly caused by hypothalamo-pituitary testicular disease. The effect of modifiable risk factors (obesity, alcohol, smoking, prescribed medications and recreational drugs) on secondary hypogonadism in a clinic-based cohort is unclear. The aim of this study was to ascertain the prevalence and effects of modifiable risk factors on secondary hypogonadism.Method: This was a retrospective, cross-sectional observational study...

Endometriotic tissues express oestrogen receptors and depend on oestrogen to proliferate, survive and cause symptoms, such as deep neuropathic pain, by recruiting neurones into the tissue. Raloxifene is an anti-oestrogen and so may prevent many of these effects and although the effect of raloxifene on endometriosis has not been directly assessed, low-dose use in a recent trial has been associated with a rapid return of pain symptoms. In this pilot study, pre-menopausal women w...

Background: Testosterone levels are commonly lowered in men with diabetes but it is unclear whether these impact upon symptoms of androgen deficiency and diabetes-related quality of life.Objective: To investigate the relationship between testosterone levels, symptoms of androgen deficiency, erectile function and diabetes-related quality of life in men with type 1 and type 2 diabetes. Design: Cross-sectional study of 115 men with type 2 diabetes, 93 men w...

Background: Recent therapeutic advances have resulted in prolonged survival of thalassemia major patients reaching adulthood and attaining reproductive capacity. However, endocrine complications are commoner in thalassemia major patients with up to 30% of patients showing hypogonadotrophic hypogonadism. Although spontaneous pregnancy have been described in well chelated and transfused patients, majority of thalassemia major patients are infertile and need assisted reproductive...

Objective: To study the role of the GnRH analogue Triptorelin in the assessment of the hypothalamic-pituitary-gonadal axis, in guiding therapy for infertility and identifying hypogonadic patients with recovery potential (functional hypothalamic dysfunction and idiopathic hypogonadotropic hypogonadism).Methods: Dynamic testing using subcutaneous injection of 100 μg Triptorelin was performed in 29 adults (11 women) with hypogonadotropic hypogonadism (...

Introduction: A sample of females (aged 19–40) was recruited from the local community to examine female health with regard to reproductive and metabolic indices. Data collected included saliva samples, anthropometrics, blood glucose, birth weight, pubertal development, health (current / previous / family history), reproductive health history and risk / diagnosis of Polycystic Ovary Syndrome (PCOS).Objectives: 1) Improve understanding of female healt...

Background: A moderately high fructose diet fed to rat dams shifts the secondary sex ratio in the litters towards males. These dams, as well as diabetic pregnant mice, have elevated plasma glucose. Hence, high uterine fluid glucose or a hormone that may mark high glucose, may result in preferential selection of Y-bearing sperm at the point of fertilisation through effects of glucose on sperm motility. In this study, we assessed sperm motility after incubation in media with/wit...

Background: Testosterone deficiency (TD) affects 5–6% of men aged 30–79 years and it can be a presenting feature of a serious underlying condition like a pituitary tumour. Clinical practice guidelines have recommended thorough investigative workup of such patients to delineate the underlying pathology in patients with secondary TD. We have undertaken a retrospective study to assess the need for expensive investigations in patients with relatively mild TD suspected to...

The aim of our study was to examine the role of mTOR-dependent intracellular signalling pathway in tle control of ovarian functions. For this purpose we have examine the effect of two mTOR inhibitors (resveratrol and rapamycin) on the release of hormones by cultured rabbit ovarian fragments. The secretion of hormones (progesterone, testosterone, estradiol and prolactin) by fragments of rabbit ovaries cultured during 48 h with and without addition of resveratrol or rapamycine (...