Endocrine Abstracts

Introduction: The human masculinisation programming window (8–14 weeks of gestation) sees testis-derived androgen drive the foetus towards a male phenotype. However, there are few systematic studies of human foetal gonad development.Aim: To conduct a pilot analysis of the foetal gonadal proteome at the end of the masculinisation programming window (13–14 weeks of gestation).Methods: Twenty-eight electively terminated foet...

Feral cat numbers in the UK are thought to number around one million and the Dogs Trust estimates it dealt with just over 110 000 stray and abandoned dogs in 2013. This scenario is common across the world and in the developing world in particular the control of feral populations is an ongoing challenge as well as a huge welfare issue. The only options currently available are expensive surgical neutering, or euthanasia of otherwise healthy animals. There is an urgent need to de...

The LH receptor (LHR) is essential for mediating multiple functions in reproduction and pregnancy. LHR belongs to the superfamily of G-protein-coupled receptors (GPCRs) that impacts nearly every aspect of human physiology and pathophysiology. Membrane trafficking is a critical mechanism for cells to decode complex signalling networks into specific downstream responses, including the signalling pathways activated by GPCRs. A detailed molecular description of GPCR trafficking is...

IGF1 plays a central role in placental growth. IGF delivered from maternal circulation binds to the IGF1 receptor (IGF1R) in syncytium resulting in the activation of Akt; inhibition of this pathway affects cytotrophoblast turnover. However, the route(s) by which IGF1 enters placenta and how its signal is delivered into the two trophoblast compartments is unknown. We have utilised quantum dots (QDs) to deliver/track IGF1 binding and internalisation in first trimester placenta (...

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: Kisspeptin stimulates hypothalamic GnRH secretion resulting in gonadotrophin release and has the potential as a future therapeutic for infertility. Previous studies have observed that kisspeptin increases LH and to a lesser degree FSH when administered to healthy women, which may limit its therapeutic potential. However, studies in women with hypothalamic amenorrhoea show that i.v. infusions of kisspeptin-54 stimulated both LH and FSH equally. Chronic s.c. infusion...

The male gonads have been exposed to various degrees of toxicants over the years and these substances affect fertility success rate. The present study investigates the effects of alcohol and/or cannabinol administration on reproductive parameters and biochemical profile in male Wistar rats. Twenty-five Wistar male rats were divided into five groups of five rats each. Group 1 served as the control, group 2 was administered methanol, 5 mg/kg BW (vehicle for cannabinol), group 3 ...

Introduction: MicroRNAs (miRNA) are a novel class of small noncoding single-stranded RNA molecules 18–24 nucleotides long that regulate gene expression at the post-transcriptional level. There is increasing evidence of their importance in polycystic ovary syndrome (PCOS), with their differential expression depending on obesity. There is recent evidence that miRNA-93 and mi-RNA-223 may have a role to play in the modulation of insulin resistance, through GLUT4 modulation in...

Failure of trophoblast invasion and remodelling of maternal blood vessels leads to the pregnancy complication pre-eclampsia (PE). Metabolomic profiling of placentas from such pregnancies has identified deranged sphingolipid metabolism as one of the pathways altered in PE. In other systems, the bioactive sphingolipid, sphingosine-1-phosphate (S1P) controls cell migration therefore this study aimed to determine its effect on extravillous trophoblast (EVT) function.<p class="...

Context: Androgen excess, obesity and hyperinsulinaemia are the cardinal features of polycystic ovarian syndrome (PCOS). While several studies have addressed the relationship between androgen excess and hyperinsulinaemia, the link between androgen excess and fat distribution remains largely undefined. Recent work has highlighted the importance of adipose tissue as an organ of androgen activation. Here, we evaluated the relationship between visceral fat and androgen excess in w...

Introduction: Accumulating evidence has shown that not only maternal health during pregnancy, but also the paternal metabolic status at the time of conception have an impact on the subsequent health of the offspring. Cholestatic liver diseases are metabolic conditions characterised by increased circulating serum bile acid and lipid levels. A previous study has shown that long-term cholestasis results in destruction of the blood–testis barrier and germ cell apoptosis. We h...

Intrauterine prostaglandin (PG) synthesis and release are key components of human labour at term and pre-term, resulting in synchronised membrane rupture, cervical dilation and myometrial contractility. A key mediator of uterine PG production is the highly inducible enzyme cyclooxygenase 2 (COX2 or PTGS2). Epidermal growth factor (EGF) is released by the foetus during pregnancy and amniotic fluid levels rise rapidly during late gestation, moreover EGF stimulates expression of ...

Single cell measurements of signalling proteins typically reveal high cell–cell variability raising questions about how reliably individual cells sense their environment in order to make decisions. Information theoretic approaches can be used to explore such sensing, treating cell signalling pathways as ‘noisy’ communication channels. Mutual information (MI) can be calculated between system inputs and outputs as a statistical measure of the reliability of sensin...

Congenital hypogonadotropic hypogonadism (CHH (MIM161110)) due to GnRH deficiency is a rare genetic disorder (affects ~1/30 000) characterised by abnormal pubertal development and infertility. Over 60% cases have anosmia (Kallmann syndrome) and some exhibit additional phenotypes. CHH is a genetically heterogeneous developmental disease. Most cases present sporadically, although familial forms (AD, AR, and X-linked) with incomplete penetrance and variable expressivity occur. Re...

Minerals and micronutrients deficiency have been reported to impair reproductive function. We investigated the influence of low salt diet and high salt diet on implantation and pregnancy in Sprague-Dawley rats. One hundred and forty-four rats were acclimatized and divided into three groups consisting of control/normal salt diet (0.3% salt), low salt diet (0.14% salt) and high salt diet (8% salt). All the rats were fed with respective diets for 6 weeks. The oestrous cycle was t...

Vitamin D-deficiency during pregnancy has been associated with increased complications of pregnancy including a high risk of pre-eclampsia (PET). Current analysis of vitamin D ‘status’ is based exclusively on analysis of maternal serum 25-hydroxyvitamin D3 (25(OH)D3), the circulating precursor form of vitamin D. We hypothesised that comprehensive profiling of vitamin D metabolites may provide a more accurate determination of vitamin D function i...

Vitamin D deficiency is prevalent in pregnant women. Active vitamin D (1,25(OH)2D3) exerts important non-classical immune-regulatory effects, and the maternal placenta (decidua) is a potential target for this. CD56+ -uterine natural killer (uNK) cells are the most prominent cell type in the decidua during early pregnancy. Given their critical role in foetal implantation and placentation, we hypothesised that uNK cells are a pivotal immunomodula...

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...

Introduction: Heavy menstrual bleeding (HMB) affects over 1 million women in the UK. At menses, progesterone (P4) withdrawal drives inflammation, tissue break-down and repair of the endometrium. Glucocorticoids are mediators of inflammation and angiogenesis. Our previous studies have demonstrated that differential endometrial expression of the glucocorticoid-metabolising enzymes, 11β-HSD-1 and -2, may play a role in HMB. We hypothesise that aberrant lo...

Background: Structured education programmes (SEP) have proved effective in changing illness perception and increasing physical activity (PA) in those with or at risk of diabetes. The SUCCESS–RCT was designed to test such a programme in women with polycystic ovary syndrome (PCOS).Methods: This was a single centre, randomised controlled trial in overweight and obese women with PCOS aimed at increasing their walking activity by 2000 steps/day after 12 ...

Gonadotropin-releasing hormone (GnRH) regulates secretion of the reproductive hormones luteinising hormone (LH) and follicle-stimulating hormone (FSH) in mammals. Homologs of GnRH have been identified in protostomian and deuterostomian invertebrates, and functional studies suggest an ancient role in regulation of reproductive physiology. The aim of this study was to characterise for the first time a GnRH-type signalling system in an echinoderm, using the starfish Asterias ...

We have reviewed the outcome of a low-dose step-up regimen for induction of ovulation in clomiphene-unresponsive women with PCOS and in women with hypothalamic hypogonadism (HH), treated at a single centre. Data from 366 women with PCOS and 80 with HH (1165 records) were entered into a FileMakerPro database, refined and constrained to allow stratification and analysis of relevant data. 85% of cycles were ovulatory in both PCOS and HH. PCOS patients were more likely to have cyc...

Background: Bile acids (BAs) are end-products of cholesterol catabolism, which act as signalling molecules to regulate glucose, lipid and energy metabolism. BAs activate several receptors including the ligand sensitive transcription factor Farnesoid X receptor (FXR) and the membrane G-protein coupled receptor, TGR5. Besides the organs physiologically in contact with BAs, like the gut and liver, BA-receptors are also expressed in cholesterol-rich steroidogenic tissues, such as ...

The aim of our studies was to examine the effect of some food, drink and medical plants and their molecules on female ovarian endocrine and other functions in vitro and in vivo. We analysed the effects of plant (green tea, rooibos, ginkgo, flaxseed, chia, yukka) extracts and plant substances (green tea polyphenols, green tea epigallocatechin-3-gallate, curcumin, resveratrol, diadzein and diosgenin) on the release of hormones and markers of proliferation, apop...

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in reproductive-aged women. Its most typical form is the association of hyperandrogenism with chronic anovulation. Theca cells (TC) of large antral and ovulatory follicles are the main source of ovarian androgens and express P450c17α, encoded by Cyp17a1, which converts progesterone to 17α-hydroxyprogesterone and androstenedione. It is known that Cyp17a1 expression in TC f...

Low birth weight has been reported in the offspring of rats fed with low salt diet. This study estimated the levels of maternal growth factors of pregnant rats fed with low salt and high salt diet. Seventy-two female Sprague–Dawley rats were acclimatized and divided into three groups consisting of control/normal salt diet (0.3% salt), low salt diet (0.14% salt) and high salt diet (8% salt). Rats were fed for six weeks and the cycles of the rats were observed in the 6th we...

Equine Chorionic Gonadotrophin (eCG) is a heterodimeric glycoprotein produced by terminally differentiated, bi/multi-nucleate trophoblast cells in the placenta of horses and humans. It is responsible for the maintenance of early pregnancy via rescue of the corpus luteum and subsequently promotion of progesterone production. The beta subunit of eCG is expressed at levels ten-fold lower than that of the alpha subunit and confers the glycoproteins specificity to the placenta. Ver...

Turner Syndrome (TS) is defined as the combination of characteristic physical features in phenotypic females and complete or partial absence of the second sex chromosome. Short stature is a constant clinical finding in patients with TS. We report the case of a 18 year old female with TS and normal stature. Primary amenorrhea was the reason for the first clinical presentation. Laboratory evaluation showed hypergonadotropic hypogonadism, low oestrogens and testosterone. A pelvic...

Background: Intramuscular long acting testosterone injections are widely used, convenient form of androgen replacement in patients with hypogonadism.Aims: To evaluate the long term effects of parenteral long acting testosterone replacement on patients commenced on treatment in years 2006–2014 and adherence to monitoring undertaken by primary care after discharge from specialist service.Method: We reviewed the results of 64 pat...

Background: Premature ejaculation (PE) is believed to be one of the most common male sexual disorders across all age groups. However its prevalence and risk factors has been rarely investigated among Nigerians. Hence, the study determined the prevalence and risk factors for erectile dysfunction (ED) especially PE among this populace.Subjects and methods: This cross-sectional survey was conducted on seventy-three (73) males aged 18-75years who were sexual...

Recently there has been reports that the administration of hormonal contraceptives alter the metabolic processes and micronutrients levels. Meanwhile some of these micronutrients are cofactors and or coenzymes of enzymes and are involved in important metabolic pathways. We compared the influence of three contraceptive methods (oral contraceptive, injectables and implants) on serum levels of Iron, ferritin, copper, ceruloplasmin and Vitamin E, using standard methods. Blood samp...

Introduction: 3-β-hydroxysteroid dehydrogenase (3BHSD) deficiency is a rare genetic disorder of steroid biosynthesis that results in decreased production of all three groups of adrenal steroids, which include mineralocorticoids, glucocorticoids, and sex steroids.Case presentation: An infant was born with ambiguous genitalia in 1975 to a conservative Muslim family and was registered as male. The child was hospitalised with addisonian crisis on the el...

Introduction: Testicular regression syndrome (TRS) or vanishing testis syndrome is a rare condition defined as the absence of testicular tissue in a genetic and phenotypic male. Rudimentary accessory structures can be present; in that case, the removal of all remnants is recommended.Case report: Male patient, 39 years old, had initially been evaluated at the age of 8 for persistent bilateral cryptorchidism. The medical documents are lacking except for a ...

Objective: This is a prospective audit looking at cardiovascular parameters in transpeople comparing those who have self medicated verses those who have not.Methods: Patients attending a workshop for new patients were questioned about cardiovascular risk factors including diabetes hypertension and smoking status. Measurements were made of lipid profile, glucose, blood pressure, waist, height and weight measurement. Those that were self medicating (SM) we...

Introduction: In addition to safety and efficacy, patient satisfaction with treatment is potentially a key factor in maintaining therapy adherence. Testosterone replacement therapy (TRT) is provided using a variety of products with different features and routes of administration. These differing product characteristics may impact on patient satisfaction and adherence with a concomitant impact on well-being and health-related quality of life. The aim of this study was to explor...

Introduction/background: Hypothalamic Amenorrhea (HA), or stress-induced anovulation, is one of the most common causes of secondary amenorrhea (1,2) and accounts for the reproductive dysfunction seen in under nutrition, excessive exercise, sever emotional stress and chronic disease. From a teleological standpoint, in the face of nutritional or physical stress, it is adaptive for an organism to allocate energy resources for its own survival rather than the costly process of rep...