Leptin, an adipocyte-derived hormone, induces a decrease in food intake and increases energy expenditure via hypothalamic interactions. In animal models obesity can be caused by leptin deficiency or by a dysfunction of the hypothalamic leptin receptor. Using a radioimmunoassay for the determination of leptin in human serum, we measured serum leptin levels in 227 otherwise healthy normal weight (N = 78; body mass index = 16.1-27.7 kg/m2) or obese women (N = 149; body mass index = 27.8-56.7 kg/m2). Fifty-three subjects were followed over a period of 12 weeks under weight reduction (800 kcal/day) and a subgroup of 33 for another 13 weeks after termination of the diet. Body mass index and serum leptin concentrations were measured longitudinally and compared to female controls not under diet. Under baseline conditions, log serum leptin levels were positively related to body mass index with a best fit using a non-linear regression (p < 0.001), indicating an attenuated increase in serum leptin levels with high body mass index. No subgroup with low serum leptin levels could be identified. Weight reduction induced a rapid decrease in serum leptin levels within the first 3 weeks to levels significantly lower than in body mass index-matched controls under normal diet (p < 0.001). This pattern was consistent after 6 and 12 weeks. Serum leptin levels increased again after the end of the diet but remained significantly lower than in the controls despite unrestricted calorie intake over 7 weeks. The rapid and persistent decrease in serum leptin to lower levels than expected from matched controls may explain the pertinent difficulties of obese subjects to cope with weight reduction.

The 'ESHRE/ASRM consensus on diagnosis, nomenclature and long-term health risks of polycystic ovarian syndrome (PCOS)' (conference in Rotterdam, Netherlands, March, 2003), which was criticized shortly after its oral presentation in 2003, is still being debated following its publication in 2004. Therefore, an extended, intensive analysis of all parameters and their combinations has been performed, differentiating between inclusion and exclusion criteria. By doing this, the profound significance of the endocrinological part of the syndrome is highlighted. The nomenclature, semantic meaning of terms, definitions, structural balancing, specificity, practicability, flexibility, limitations and reproducibility for both individualization, as well as grouping from the clinical and scientific perspective, have been examined in detail. This analysis supports previous critical comments, and reaches the conclusion that the recommendations of the consensus lack accuracy and specificity, a weakness that results in the risk of overdiagnosis and in a lack of reproducibility. Altogether, they fail to fulfil the criteria of universal guidelines on several levels. Instead, a profound paradigm shift is demanded, from an inconsistent perception to a more systematic, balanced and comprehensive view. A short indication on an alternative sweeping concept of a strictly defined, therapy-targeted classification and diagnostic procedure of female functional androgenization is presented.

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Insulin-like growth factors (IGFs) belong to a family of low mol. wt, single chain polypeptides inducing growth promotion and insulin-like metabolism effects and regulating both cell replication and differentiation. Recent studies in laboratory animals suggest that IGFs play an important role as intraovarian regulators in several mammalian species. The purpose of this article was to review current concepts of interactions between the IGFs and the thecal-granulosa-cell function. To provide a basic understanding of these interactions, we have first analysed data concerning biosynthesis, biochemical structure, pharmacokinetics, degradation, binding proteins and receptors for IGFs. Then we have discussed the specific interactions between IGFs and theca-granulosa-cell regulation, and analysed the significance of the relationship to the pathophysiology of some endocrine and reproductive disorders, including hyperandrogenism and female infertility.

Increasing evidence suggests that insulin-like growth factors (IGFs) play an important role as intra-ovarian regulators in several mammalian species. Recently, we and others have reported the presence of both IGF-I and IGF-II in human follicular fluid. The source of these follicular IGFs, however, has not been determined. In this study, we have evaluated the possibility that human ovarian granulosa cells are a production site of IGFs in vivo. We used cDNA probes to analyse directly IGF-I and IGF-II gene expression at the level of mRNA content in granulosa cells from preovulatory follicles of women undergoing either gamete intra-Fallopian transfer or in-vitro fertilization. Samples of granulosa cell RNA enriched for polyadenylated RNA [poly(A)+RNA] were hybridized with probes for human IGF-I, human IGF-II and human actin (as a control). Transfer blot analysis revealed that the enriched poly(A)+RNA of human granulosa cells from preovulatory follicles contained no detectable IGF-I mRNA. In contrast, three species of IGF-II mRNA of approximately 6.1, 4.9 and 2.1 kb were detected. These data suggest that IGF-II mRNA, but not IGF-I mRNA, is expressed in human granulosa cells collected immediately before ovulation. Our results support the concept that human ovarian IGF-II is produced locally and may function in an autocrine or paracrine fashion in the human ovary in vivo.