The polycystic ovary syndrome evolutionary paradox: a genome-wide association studies-based, in silico, evolutionary explanation.

Objective: In this study we analyze the PCOS phenotype-genotype relationship in silico, using SNPs of representative genes for analysis of genetic clustering and distance, to evaluate the degree of genetic similarity. Data Source: 1000 Genomes, HapMap, and Human Genome Diversity Project databases were used as source of allele frequencies of the SNPs, using data from male and female individuals grouped according to their geographical ancestry. Setting and Design: Genetic clustering was calculated from SNPs data by Bayesian inference. The inferred ancestry of individuals was matched with PCOS phenotype data, extracted from a previous meta-analysis. The measure of genetic distance was plotted against the geographic distance between the populations. Results: The individuals were assigned to five genetic clusters, matching with different world regions (Kruskal-Wallis/Dunn's post test; P < .0001), and converging in two main PCOS phenotypes in different degrees of affinity. The overall genetic distance increased with the geographic distance among the populations (linear regression; R2 = 0.21; P < .0001), in a phenotype-unrelated manner. Conclusions: Phenotype-genotype correlations were demonstrated, suggesting that PCOS genetic gradient results from genetic drift due to a serial founder effect occurred during ancient human migrations. The overall prevalence of the disease supports intralocus sexual conflict as alternative to the natural selection of phenotypic traits in females

Response to letter by Azziz R., et al.

Comment on The polycystic ovary syndrome evolutionary paradox: a genome-wide association studies-based, in silico, evolutionary explanation. [J Clin Endocrinol Metab. 2014] Letter to the editor re: Casarini and Brigante, 2014, from Azziz R., et al. [J Clin Endocrinol Metab. 2015

Is polycystic ovary syndrome a sexual conflict? A review

Several studies have attempted to explain the high overall prevalence of polycystic ovary syndrome among women worldwide (about 4-10%) despite its link to subfertile phenotypes. For this reason, it is considered an evolutionary paradox. In this review, we show that several genetic loci associated with the disease differently modulate the reproductive parameters of men and women. This observation suggests that such genetic variants lead to opposite effects in the two sexes in reproductive success. Intralocus sexual conflict as a cause of the persistence polycystic ovary syndrome genotypes among humans is supported

Two hormones for one receptor: evolution, biochemistry, actions and pathophysiology of LH and hCG

Luteinizing hormone (LH) and chorionic gonadotropin (CG) are glycoproteins fundamental for sexual development and reproduction. Since they act on the same receptor (LHCGR), there is a general consensus that LH and hCG are equivalent. However, separate evolution of LHβ and hCGβ subunits occurred in primates, resulting in two molecules sharing ∼85% identity and regulating different physiological events. Pituitary, pulsatile LH production results in a ∼90 min half-life molecule targeting the gonads, to regulate gametogenesis and androgen synthesis. Trophoblast hCG, the "pregnancy hormone", exists in several isoforms and glycosylation variants with long half-lives (hours), angiogenic potential, and acts on luteinized ovarian cells as a progestational. The different molecular features of LH and hCG lead to hormone-specific LHCGR binding and intracellular signaling cascades. In ovarian cells, LH action is preferentially exerted through kinases, pERK1/2 and pAKT, resulting in irreplaceable proliferative/anti-apoptotic signals and partial agonism on progesterone production in vitro. In contrast, hCG displays notable cAMP/PKA-mediated steroidogenic and pro-apoptotic potential, which is masked by estrogen action in vivo. In vitro data are confirmed by large dataset from assisted reproduction, since the steroidogenic potential of hCG positively impacts on the number of retrieved oocytes, while LH impacts pregnancy rate (per oocyte number). Interestingly, Leydig cell in vitro exposure to hCG results in qualitatively similar cAMP/PKA and pERK1/2 activation as compared to LH, as well as testosterone. The supposed equivalence of LH and hCG is debunked by such data highlighting their sex-specific functions, thus deeming it an oversight caused by incomplete understanding of clinical data

Effect of the Glucagon-Like Peptide-1 Receptor Agonists on Autonomic Function in Subjects with Diabetes: A Systematic Review and Meta-Analysis

Background: In addition to the metabolic effects in diabetes, glucagon-like peptide 1 receptor (GLP-1R) agonists lead to a small but substantial increase in heart rate (HR). However, the GLP-1R actions on the autonomic nervous system (ANS) in diabetes remain debated. Therefore, this meta-analysis evaluates the effect of GLP-1R agonist on measures of ANS function in diabetes. Methods: According to the Cochrane Collaboration and Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, we conducted a meta-analysis considering clinical trials in which the autonomic function was evaluated in diabetic subjects chronically treated with GLP-1R agonists. The outcomes were the change of ANS function measured by heart rate variability (HRV) and cardiac autonomic reflex tests (CARTs). Results: In the studies enrolled, HR significantly increased after treatment (P&lt;0.001), whereas low frequency/high frequency ratio did not differ (P=0.410); no changes in other measures of HRV were detected. Considering CARTs, only the 30:15 value derived from lying-to-standing test was significantly lower after treatment (P=0.002), but only two studies reported this measurement. No differences in other CARTs outcome were observed. Conclusion: The meta-analysis confirms the HR increase but seems to exclude an alteration of the sympatho-vagal balance due to chronic treatment with GLP-1R agonists in diabetes, considering the available measures of ANS function

Endoscopic transsphenoidal approach as a promising surgical option in the treatment of craniopharyngioma

10.1530/endoabs.32.P85

Prevalence and characterization of hypogonadism among men with human immunodeficiency virus infection: preliminary results

Preliminary results on the prevalence of male hypogonadism in HIV-infected me

Thyroid ultrasound alterations occurrence in patients with previous negative examination: A 6-years observational follow-up trial

10.1530/endoabs.56.P105

Effects of treatment for acromegaly on Bone Mineral Density (BMD): is Pegvisomant protective on lumbar BMD?

The abstract deals with the different effects of treatments for acromegaly on bon