Endocrine Abstracts

The principal physiological effect of the anterior pituitary hormone prolactin is to stimulate milk production during lactation. However, recombinant mouse prolactin (PRL) has recently been shown to have an antidiuretic effect when the normal antidiuretic hormone, vasopressin, is either absent from the circulation or its secretion inhibited(1). The present study was designed to investigate whether this antidiuretic effect of prolactin was mediated by changes in the glomerular ...

Introduction: Studies have suggested that PCOS is associated with increased cardiovascular (CVS) risk. The mechanisms that may contribute to increased CVS susceptibility include endothelial dysfunction, vascular inflammation and atherothrombosis.Aim: To compare CVS risk profiles in women with PCOS and healthy age and weight matched controls using novel biochemical and biophysical markers of these pathological processes.Method: Fo...

Aim: To evaluate the effects of cyproteronacetate/ethinylestradiol (Diane 35) on weight, lipid and androgen levels in women with PCOS.Methods: 19 PCOS women, age 24.3 +/- 4.3 yrs, weight (W) 66.3 +/- 13.5 kg. Blood samples in the early follicular phase of menstrual cycle for cholesterol (C), HDL cholesterol (HDL-C), triglycerides (TG), testosterone (T), androstenedione (A), DHEAS and SHBG and again after 7 +/- 3.8 months of treatment with Diane 35.<p...

The effects of N-terminal parathyroid hormone (PTH) and parathyroid hormone related peptides (PTHrP) on the spontaneous contractility of 4 days pregnant mouse uterus in vitro were investigated. The myometrial tissue contracted vigorously for several hours, when incubated in organ baths in De Jalon's solution. PTH(1-34) and PTHrP(1-40) caused similar dose related inhibitions of contractions over a dose range of 10-9 to 10-7 M. C terminal PTHrP(107-139) was devoid of this...

Background: PCO is more prevalent among SA than C and IR is central to its pathogenesis; whilst Type 2 diabetes (DM) is commoner in SA. We compared the phenotype and IR in South Asian and Caucasians with PCOS.Methods: Comparison of consecutive anovular PCOS; 47 SA and 36 Caucasians and their age and weight matched controls (11 SA and 22 Cs).Results: SA presented earlier (age 26 plus/minus 4 v 30.1 plus/minus 5, p = 0.005). BMI (24....

Macroprolactin, a high molecular mass complex of prolactin and an IgG antibody is confined to the vasculature and exhibits limited bioactivity in vivo. Using a panel of sera obtained from 10 subjects whose hyperprolactinaemia was due entirely to macroprolactin this study aims to compare the level of detection of macroprolactin by 9 of the most commonly used prolactin immunoassays.The study involved 24 clinical laboratories employing the following 9 anal...

BACKGROUND: There are wide ethnic differences in women's attitude to the menopause and hormone replacement therapy (HRT). We have surveyed the awareness and attitudes of Libyan women to the menopause and HRT. METHODS: An anonymous self-administered questionnaire on the knowledge and attitudes towards menopause and HRT was used. 353 women were studied (median age 31(20-60) years; 188 married, 157 single and 8 divorced/widowed). Majority had secondary (38%) or university (51%) e...

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Oxytocin drives parturition by contracting the uterus, but transgenic mice with no oxytocin appear to give birth normally. We have previously shown that oxytocin antagonist administration delays births showing that oxytocin plays a role in normal mouse parturition. Here, we tested the hypothesis that oxytocin neurones are active during parturition, using double immunocytochemistry for Fos and oxytocin to show neuronal activation and radioimmunoassay of blood samples to seek in...

Cytotoxic chemotherapy is a well recognised cause of premature ovarian failure (POF). A proportion of women with biochemical evidence of POF following treatment recover ovarian function with a return of normal menses and fertility, but there are no indicators that allow the identification of this subgroup of patients. In addition, we have previously reported only minor reductions in BMD in a cohort of women with POF following cytotoxic chemotherapy and had postulated that this...

Hirsutism in women with polycystic ovary syndrome (PCOS) is associated with hyperandrogenism and insulin resistance. The insulin sensitising agent metformin can reduce hyperandrogenism in women with PCOS. Conventional treatment for hirsutism in such women is combined anti-androgen and estrogen (Dianette; Schering Ltd). The aim of this study was to compare the clinical efficacy of Dianette with metformin (Glucophage; Merck, 500mgs tds) in the treatment of hirsutism in women wit...

A 29 year old male and his wife presented with an 18 month history of primary infertility. History and initial investigations suggested no major female component but a semen analysis revealed azoospermia. There was no history of any sexual dysfunction and neither partner was receiving any medication. Clinical examination revealed normal secondary sexual characteristics. Both testicles were of normal consistency with a volume of approximately 15mls but a 4x2cm mass was palpable...

Studies on breast cancer cell lines, placental microsomes and purified recombinant enzymes have shown that various phytoestrogens can inhibit both aromatase and 17beta-hydroxysteroid dehydrogenase (HSD) enzymes. This has led to the suggestion that certain phytoestrogens may exert their endocrine disrupting functions by enzyme inhibition rather than their ability to bind weakly to oestrogen receptors. Previous studies have shown that genistein, the active ingredient of soy, ind...

11 beta-hydroxysteroid dehydrogenase type 2 (11 beta-HSD2) is responsible for the conversion of hormonally active cortisol (F) to inactive cortisone (E), and is expressed in mineralocorticoid target tissues (kidney, colon). However, the most abundant source of this enzyme is human placenta, notably placental trophoblast where it is thought to protect the fetus from maternal hypercortisolaemia and play a role in fetal growth and development. During gestation placental trophobla...

Androgen deficiency may contribute to sexual dysfunction in hypoadrenalism but its role in normal female physiology is uncertain. The aim of this study was to determine the role of androgens in the aetiology of sexual dysfunction in healthy women. Twenty-nine premenopausal women with loss of libido (subjects) and 13 healthy females (controls) were studied. They were aged 18 to 45 years and in a stable heterosexual relationship. Venous blood was taken at 9 am in the follicular ...

Introduction:Vascular endothelial growth factor (VEGF), a potent angiogenic growth factor, has been implicated in various disease states, particularly pre-eclampsia. VEGF exerts its biological activities through two different receptor tyrosine kinases: KDR and Flt-1. Alternative splicing of Flt-1 pre-mRNA produces two products, one encoding the full-length receptor and the other a soluble form, sFlt-1. As sFlt-1 inhibits VEGF activities the regulation of...

The association of hyperandrogenism and insulin resistance is common in several syndromes. The proposed mechanism is the stimulation of ovarian theca cells by insulin to produce testosterone. Weight loss, improves insulin resistance, reduces insulin levels and consequently decreases circulating androgens.Material and methods:Ten female subjects with severe obesity and hyperandrogenism were evaluated before and after weight loss at...

BACKGROUND: DHEA and DHEAS, can be converted into Androstenedione, T and DHT as well as oestrogens by peripheral tissues. In normal men the conversion rate of IV-infused radiolabelled DHEAS to T is only 0.7%. In hypogonadal men, this conversion rate may be increased. We hypothesise that a pharmacological dose of orally administered DHEA may be able to raise plasma T into the normal range in hypogonadal men. METHODS: Local Ethical Committee Approval was obtained. Two groups (n=...

OBJECTIVE Measurement of serum testosterone level is an integral part of the assessment of men presenting to endocrine clinics. Little is known about variation of testosterone level by ethnic group. The principal determinant of testosterone bioavailability is sex hormone binding globulin (SHBG) which itself is a marker for insulin sensitivity. Our aim was to examine variations in testosterone and SHBG levels across three ethnic groups in relation to ethnic differences in insul...

Homeobox (HOX) genes encode proteins that are important in normal foetal development. Some of these genes such as HOXA10 also appear to be involved in haematopoiesis, tumour invasion and normal uterine function. HOXA10 is sensitively regulated by hormonal changes during the menstrual cycle. In addition, knockout mouse studies have suggested a role for HOXA10 in implantation but its precise mechanism of action remains unclear. To further investigate HOXA10 function in human rep...

Metformin has gained a reputation as an effective fertility treatment in PCOS. Most publications use ovulation rate as the main outcome measure and few quote pregnancy rates. We have audited the first 39 patients with PCOS treated with Metformin in our Reproductive Unit. In this practice, as opposed to a research setting, there were often multiple factors contributing to infertility and they were usually proven resistant to other forms of treatment.In t...

The role of the intra-ovarian insulin-like growth factor (IGF) system in preantral follicle development is unclear. Here we have examined the expression of mRNA for insulin-like growth factor-1 (IGF-1), IGF-2, Type 1-IGF receptor, Type 2-IGF receptor and insulin receptor (IR) in human pre-antral follicles at different stages. Ovarian cortex biopsies (5mm3) were obtained (with informed consent) during gynaecological surgery from six women (age 32.2 plus/minus SD 2.2,...

In vitro maturation (IVM) of oocytes obtained from medium sized antral follicles could avoid the need for superovulation for in vitro fertilisation. FSH is routinely added to culture media during IVM but the effects on oocyte health are unclear. The aim of this study was to assess the effect of FSH on 1) the metabolic activity of individual mouse cumulus-oocyte-complexes (COCs) matured in vitro,and 2) the genesis of chromosomal abnormalities. 274 mouse COC...

Introduction. We have previously used a synthetic phage display library to derive single chain (ScAbs) antibodies which bind GnSAF bioactivity in-vitro. However, recovery of GnSAF using the ScAbs, which tended to aggregate and become unstable, was limited. We have therefore engineered these ScAbs into full-length human IgG forms.Methods. CDR regions from soluble expression plasmids for two different GnSAF-recognising ScAbs were amplified by PCR. Two uni...

There is evidence from animal studies that 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) is essential for normal reproductive function. Vitamin D deficient rats have reduced fertility, and VDR null mutant mice demonstrate impaired folliculogenesis. We have recently demonstrated that 1,25(OH)2D3 suppressed the production of oestradiol (E2) independently of progesterone (P) in luteinised, but not in non-luteinised human granulosa cells, suggesting that 1,25(OH)<s...

Serum of infertile males and that of proven fathers (n=717) was analysed for the measurement of sperm concentration, serum LH, FSH and testosterone. Earlier, when classified on the basis of sperm count, 13% males turned out to be azoospermic, 15% oligozoospermic, 0.025% polyzoospermic and 42% normozoospermic in a five year analysis. Oligozoospermic subjects were further classified as mild, moderate and severe oligozoospermic. Hormonal analysis indicated normal levels of LH and...

Asthenozoospermia was seen in 43% patients (n = 516), either singly, or in combination with other semen disorders. For this study, 186 patients were divided into two groups of 93 patients each. In the treated group, the patients were advised vitamin A and E therapy for 12 weeks, while the placebo group was not administered anything. In all the patients in the treated group, sperm motility increased significantly (p < 0.05). The mean motility increase in the treated group w...

Introduction Tissue remodelling, and deposition of extracellular matrix and basement membrane are critical processes in the formation and development of ovarian follicles. Collagen is a major component of the ECM. Though there is substantial literature concerning the breakdown of collagen in the ovary, little attention has been given to the processes of collagen formation and deposition. Lysyl oxidase (LO) is critical in this process, being the enzyme responsible for the final...