Keynote Lecture 22 Feb 2007: Andrea Dunaif, Society for Endocrinology Visiting Professor

Society for Endocrinology Visiting Professor: Andrea Dunaif
Date: Thursday 22^nd February 2007
Venue: Clinical Learning Centre, RVI, Newcastle

09:30 Tea, coffee, OJ & biscuits downstairs
10:00 Dr Richard Quinton: Welcome & Introduction
10:10 Dr Anna Jovanovitch: The 2^nd meal effect: a physiologic means of limiting postprandial hyperglycaemia
10:30 Dr Andy James: 1. A case of acromegaly? 2. A case of acanthosis nigricans?
11:10 Dr B Ravikumar: Prevalence of assay interference in women with high serum testosterone levels
11:30 Dr IM Ibrahim: The Pro12Ala variant of PPARγ2 influences insulin sensitivity in healthy subjects
11:50 Dr Ebaa Al-Ozairi: Investigation & management of severe postmenopausal hyperandrogenism
12:10 Cold buffet downstairs
13:00 Prof A Dunaif: Cellular, molecular and genetic mechanisms of insulin resistance in PCOS

Contact: Richard Quinton

Thumbnail biography
Professor Andrea Dunaif, MD
Charles F. Kettering Professor of Medicine
Chief, Division of Endocrinology, Metabolism and Molecular Medicine
NorthWestern University, Chicago, USA

Genetic and molecular basis of Polycystic ovary syndrome (PCOS)
Polycystic ovary syndrome (PCOS) is the most common cause of both hormonally-related infertility and oligomenorrhea. PCOS is also associated with profound insulin resistance and a ~ 7-fold increased risk for type 2 diabetes mellitus. PCOS, as well as the insulin resistance associated with it, appear to be genetic defects. Moreover, insulin resistance plays a causal role in the abnormalities of ovarian steroidogenesis as well as the anovulation characteristic of PCOS. There are three major research projects currently ongoing. The approaches range from large-scale family studies through intensive patient-oriented research to animal models and cellular and molecular biology. PCOS is the human disease model. This syndrome is characterized by increased androgen biosynthesis and disordered gonadotropin secretion. It is among the most common endocrine disorders of women, the leading cause of hormonally-related infertility and a major risk factor for type 2 diabetes mellitus.

Research Topics
Genetic Analysis of Polycystic Ovary Syndrome (PCOS)
Insulin Action and Secretion in PCOS
Fetal Origins of PCOS

The Genetic Basis of PCOS
This research program focuses on identifying the susceptibility genes for PCOS, performing genotype-phenotype analyses and identifying environmental and genetic factors contributing to PCOS familial phenotypes. Studies include family studies with linkage analysis and detailed analyses of reproductive function and insulin action in women with PCOS and their relatives. The approaches include statistical genetics and in vivo studies of insulin action and secretion, as well as pulsatile gonadotropin secretion. One susceptibility gene region has been identified on chromosome 19p13.2 close to the insulin receptor gene. This research is supported by the NIH-NICHD National Cooperative Program for Infertility Research.

Insulin Action and Secretion in PCOS
These studies are focused on identifying the cellular and molecular mechanisms of defects in insulin action and secretion in PCOS. Approaches include detailed in vivo studies of these parameters utilizing techniques such as the euglycemic glucose clamp, frequently sampled intravenous glucose intolerance test with minimal model analysis and graded glucose infusions. Insulin receptor signal transduction is examined in human skeletal muscle biopsies, as well as in human skeletal muscle and adipocyte cultures. Intrinsic defects in insulin receptor signaling have been identified and the mechanisms of these abnormalities are currently under investigation. These studies are supported by an NIH-NICHD-ORWH Specialized Center of Research (SCOR) on Sex and Gender Factors Affecting Women’s Health.

Fetal Origins of PCOS
These studies examine the impact of prenatal androgen exposure on insulin action in rodent, primate and sheep models. Studies include examination of lipolysis and insulin signaling in skeletal muscle and adipose tissue and the molecular mechanism of fetal programming. These studies are supported by an NIH-NICHD-ORWH Specialized Center of Research (SCOR) on Sex and Gender Factors Affecting Women’s Health.

updated 20th February
updated 21st February