The purpose of this study was to find out the clinical utility of PRL in patients with early and advanced breast cancer. Patients with stage II and stage III disease were followed for a period of 5 and 3 years, respectively or until death within the stipulated time. Circulating PRL was assayed preoperatively and sequentially threrafter from III patients with breast cancer. Immunohistochemical localisation of PRL and PRLR was performed on formal in fixed, paraffin embedded tissue sections. Tumoral PRLR was estimated by ligand binding assay, and expression of PRL mRNA and PRLR mRNA was carried out by RTPCR. Further, the RTPCR PRL amplimer was sequenced. Expression of PRL isoforms in serum and cytosol samples was studied. Hyperprolactinemia (PRL>20.0 ng/ml serum) was observed in 58% of the breast cancer patients. Univariate analysis showed that patients with hyperprolactinemia had a significantly shorter overall survival than patients with PRL <20.0 ng/ml serum (P = 0.0001). Similar results were observed when patients were grouped according to disease stage. Changes in serial PRL levels showed excellent correlation with response to therapy and progression of disease, and accurately indicated the response and development of resistance to TAM in these patients. Seventy eight percent of the tumors showed positive immunoreactivity with PRL antibody. PRL mRNA expression was seen in 52% of the tumors. Sequence analysis of the 234 bp PRL amplimer revealed that the sequence was homologous to the sequence of exon 5CR PRL transcript in breast tumors. mRNA. Western hybridization showed the presence of three isoforms of PRL protein in serum and tumor cytosols of breast cancer patients. The action of PRL is mediated by PRLR and it was observed that the PRLR positivity by ligand binding assay was 23% where as with immunohistochemistry the positivity was 80%. The expression of PRLR mRNA by RT-PCR showed two forms of PRLR mRNA i.e. the long form (800-900 bp), seen in 22% of the tumors and the intermediate forms of (500-600 bp), seen in 54% of the tumors. This multifaceted study of PRL suggests that breast cancer cells produce PRL and this ectopically produced PRL might be acting as a major local growth promoter via autocrine and paracrine mechanisms. It may provide new insights into endocrine treatment of breast cancer.

Only few studies on zinc status in hypogonadotropic hypogonadism patients are available from India; however no study has been reported on the therapeutic effect of zinc supplementation on these patients. The present study was undertaken to assess the zinc status and hormonal profile in patients presenting with isolated hypogonadotropic hypogonadism and then to assess the therapeutic effect of zinc supplementation in those patients found to be zinc deficient. Zinc supplementation study on hypogonadism patients showed good improvement in terms of erythrocyte and hair zinc levels and also showed improvement in testosterone levels in a proportion of patients. When clinically evaluated. 67% of the patients have shown improvement suggesting that zinc therapy can be effectively used to treat a subset of patients with hypogonadotropic hypogonadism.

The clinical features and urinary hormonal levels were correlated in twenty women with polycystic ovaries. Significantly elevated urinary luteinising hormone (LH) to follicle stimulating hormone (FSH) ratio and estrone glucuronide levels (ElG) were observed in these 20 women (P < 0.001). It was also observed that obesity, hirsutism, amenorrhea and elevated testosterone levels were common (12/20) in group with enlarged ovaries. The study documents the utility of urinary hormone assay with well established reference values in screening women with polycystic ovarian syndrome.

DAG-PKC is a major pathway by which hyperglycemia induces vascular complications in diabetes mellitus. Although the correlation between the activation of DAG-PKC and diabetes vascular and neurological complications is substantial in rodent models of diabetes, there is not much human data because it is difficult to obtain fresh vasculature or neurological tissues for the measurement of DAG-PKC levels. A PKC (isoform inhibitor is only useful in diabetic patients if the same profile of PKC isoforms are activated or expressed in there patients and in the diabetic rodent models. In addition, the secondary markers of PKC activation need to be identified since they can be used to monitor the effectiveness of PKC inhibitor when treated with intensive glycemic control or PKC inhibitor. Progress has been made to identify some of these potential secondary parameters of vascular pathologies such as levels of VEGF, changes in the retinal haemodynamics and endothelial cell functions. These results are only suggestive. Definitive studies are on going and should determine clearly the role of DAG-PKC in the development of the various complications of diabetes mellitus. The clinical trials are now in progress using PKC isoform specific inhibitor in determining the role of activation of DAG-PKC in the vascular complications in diabetic patients. The PKCs may prove ultimately to be suitable targets for therapeutic interventions when their basic regulation in diabetic complications is better understood.