Increased protein expression of LHCG receptor and 17a-hydroxylase/17,20-lyase in human polycystic ovaries

STUDY QUESTION Does the expression of LHCG receptor (LHCGR) protein and key enzymes in the androgen biosynthetic pathway differ in normal human versus polycystic ovarian tissue? SUMMARY ANSWER LHCGR and 17a-hydroxylase/17-20-lyase (CYP17A1) protein levels are increased in polycystic ovaries (PCOs). WHAT IS KNOWN ALREADY The predominant source of excess androgen secretion in women with polycystic ovary syndrome (PCOS) is ovarian theca cells but few studies have directly assessed the presence and abundance of protein for key molecules involved in androgen production by theca, including LHCGR and the rate-limiting enzyme in androgen production, CYP17A1. STUDY DESIGN, SIZE, DURATION This is a laboratory-based, cross-sectional study comparing protein expression of key molecules in the androgen biosynthetic pathway in archived ovarian tissue from women with normal ovaries (n = 10) with those with PCOs (n = 16). PARTICIPANTS/MATERIALS, SETTING, METHODS A quantitative morphometric study was performed using sections of archived human ovaries (n = 26) previously characterized as normal or polycystic. The distribution and abundance of LHCGR, CYP17A1, 3ß-hydroxysteroid dehydrogenase type 2 (3ßHSDII) and 17ß-hydroxysteroid dehydrogenase type 5 (17ßHSD5) proteins were evaluated by immunohistochemistry and quantified. MAIN RESULTS AND THE ROLE OF CHANCE A higher proportion of theca cells from anovulatory PCO expressed LHCGR protein when compared with control ovaries (P = 0.01). A significant increase in the intensity of immunostaining for CYP17A1 was identified in antral follicles in sections of PCO compared with ovaries from normal women (P = 0.04). LIMITATIONS, REASONS FOR CAUTION As the study used formalin-fixed ovarian tissue sections, it was not possible to carry out studies ‘in vitro’ using the same ovarian tissues in order to also demonstrate increased functional activity of LHCGR and CYP17A1. WIDER IMPLICATIONS OF THE FINDINGS The data are in keeping with the results of previous studies in isolated theca cells and support the notion of an intrinsic abnormality of theca cell androgen production in women with PCOS. STUDY FUNDING/COMPETING INTEREST(S) The research was supported by a Programme Grant, G0802782, from the Medical Research Council (MRC) UK and by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Imperial College Healthcare NHS Trust and Imperial College London. F.V.C was supported by Capes Foundation (Brazilian Ministry of Education). The authors have no conflicts of interest to disclose

Disorders of follicle development and steroidogenesis in ovaries of androgenised foetal sheep

The prenatally androgenised (PA) sheep is a well-recognised model for the study of developmental programming of adult polycystic ovary syndrome (PCOS). Most of the studies to date have involved examination of the reproductive and metabolic effects in the offspring after puberty, but more recently, it has been reported that there is disruption of follicle formation and steroid gene expression in ovaries of foetal sheep after exposure of the mother to excess androgen. Our study examines evidence for precocious primordial follicle formation at day 90 of gestation in ovaries of foetal Poll Dorset sheep. Using a specific marker of germ cells (VASA homologue protein) in ovarian sections, we found that androgenised sheep had nearly double the proportion of germ cells enclosed in follicles compared with control animals. When analysed by follicle stage, there was no significant difference between groups in the proportion of primordial follicles and growing (transitional and primary) follicles. Differences between PA and control foetal sheep were found in both mRNA and in protein expression of steroidogenic enzymes and androgen receptor. Our results in Dorset ewes are complementary to previous reports, but suggest that the timing of follicle formation and steroidogenic activity may vary between different breeds as well as in response to androgen. These data show that granulosa cells constitute a specific target for programming by androgen in utero and raise key questions about the role of exposure to androgen in utero in developmental origins of PCOS

Protective effect of yerba mate intake on the cardiovascular system: a post hoc analysis study in postmenopausal women

<div><p>The prevalence of cardiovascular and metabolic diseases is increased in postmenopausal women, which contributes to the burden of illnesses in this period of life. Yerba mate (Ilex paraguariensis) is a native bush from Southern South America. Its leaves are rich in phenolic components, which may have antioxidant, vasodilating, hypocholesterolemic, and hypoglycemic proprieties. This post hoc analysis of the case-control study nested in the Obesity and Bone Fracture Cohort evaluated the consumption of yerba mate and the prevalence of hypertension, dyslipidemia, and coronary diseases in postmenopausal women. Ninety-five postmenopausal women were included in this analysis. A questionnaire was applied to evaluate the risk factors and diagnosis of cardiovascular diseases and consumption of yerba mate infusion. Student's t-test and chi-square test were used to assess significant differences between groups. The group that consumed more than 1 L/day of mate infusion had significantly fewer diagnoses of coronary disease, dyslipidemia, and hypertension (P<0.049, P<0.048, and P<0.016, respectively). Furthermore, the serum levels of glucose were lower in the group with a higher consumption of yerba mate infusion (P<0.013). The serum levels of total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides were similar between the groups. This pragmatic study points out the benefits of yerba mate consumption for the cardiovascular and metabolic systems. The ingestion of more than 1 L/day of mate infusion was associated with fewer self-reported cardiovascular diseases and lower serum levels of glucose. Longitudinal studies are needed to evaluate the association between yerba mate infusion and reduction of cardiovascular diseases in postmenopausal women.</p></div