Leptin is a mainly adipocyte-secreted protein that was discovered 5 years ago. Most of the research following this discovery focused on the role of leptin in body weight regulation, aiming to illuminate the pathophysiology of human obesity. However, more and more data are emerging that leptin is not only important in the regulation of food intake and energy balance, but that it also has a function as a metabolic and neuroendocrine hormone. It is now clear that it is especially involved in glucose metabolism, as well as in normal sexual maturation and reproduction. Besides this, interactions with the hypothalamic-pituitary-adrenal, thyroid and GH axes and even with haematopoiesis and the immune system have also been described. It has been shown that leptin secretion by the adipocyte is partly regulated by other hormones, such as insulin, cortisol, and sex steroids, mainly testosterone. Also, other hormones like thyroid hormone and GH are possibly involved in leptin synthesis. Leptin itself exerts effects on different endocrine axes, mainly on the hypothalamic-pituitary-gonadal axis and on insulin metabolism, but also on the hypothalamic-pituitary-adrenal, thyroid and GH axes. Leptin may thus be considered a new endocrine mediator, besides its obvious role in body weight regulation.

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Human leptin: from an adipocyte hormone to an endocrine mediator.

Whilst many multiparous women are obese (body mass index >30 kg/m(2)), obesity has been associated with impaired fecundity; however, the mechanism which links obesity to reduced fertility remains to be fully elucidated. Obese women, particularly those with central obesity, are less likely to conceive per cycle. Obese women suffer perturbations to the hypothalamic-pituitary-ovarian axis, menstrual cycle disturbance and are up to three times more likely to suffer oligo-/anovulation. A fine hormonal balance regulates follicular development and oocyte maturation, and it has been observed that obesity can alter the hormonal milieu. Leptin, a hormone produced by adipocytes, is elevated in obese women, and raised leptin has been associated with impaired fecundity. Obesity impairs ovulation but has also been observed to detrimentally affect endometrial development and implantation. The expression of polycystic ovary syndrome (PCOS) is regulated, in part, by weight, and so obese women with PCOS often have a more severe phenotype and experience more subfertility. Obesity also impairs the response of women to assisted conception treatments. Weight loss through lifestyle modification or bariatric surgery has been demonstrated to restore menstrual cyclicity and ovulation and improve the likelihood of conception. In this article, we will discuss the effect of obesity upon key reproductive mechanisms and its relation to fertility treatments.

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The adverse effects of obesity on conception and implantation

This review summarizes clinical studies in which glutathione was measured in tumor tissue from patients with brain, breast, gastrointestinal, gynecological, head and neck and lung cancer. Glutathione tends to be elevated in breast, ovarian, head and neck, and lung cancer and lower in brain and liver tumors compared to disease-free tissue. Cervical, colorectal, gastric, and esophageal cancers show both higher and lower levels of tumor glutathione. Some studies show an inverse relationship between patient survival and tumor glutathione. Based on this survey, we recommend approaches that may improve the clinical value of glutathione as a biomarker.

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Glutathione levels in human tumors.

Obesity and overweight are common conditions in the developed countries and they carry many health consequences, including some reproductive disorders. There is a very high prevalence of obese women in the infertile population and many studies have highlighted the link between obesity and infertility. A large proportion of infertile women have polycystic ovary syndrome (PCOS) which is also linked with increased risk of obesity and other metabolic anomalies. The association between obesity and/or PCOS and hyperinsulinaemia, hyper androgenism and abnormal secretion of other hormones, such as leptin, underlies many reproductive disorders observed in this population. It has been demonstrated that weight loss can improve the fertility of obese women through the recovery of spontaneous ovulation, whereas others will have improved response to ovarian stimulation in infertility treatment. Therefore, it is proposed that following the initial assessment of infertility and body mass index or other measurement of obesity, various weight management interventions, including diet, exercise or pharmacotherapeutic approaches, should be considered for overweight and obese infertile women.

/pdf/improving-reproductive-performance-in-overweight-obese-women-55sxqvw536.pdf

Improving reproductive performance in overweight/obese women with effective weight management

The role of low-grade inflammation in the polycystic ovary syndrome

Glutathione and its metabolizing enzymes in patients with different benign and malignant diseases.

Serum leptin as an additional possible pathogenic factor in polycystic ovary syndrome

Detection of survivin protein in aqueous humor and serum of retinoblastoma patients and its clinical significance.

Purpose To evaluate the diagnostic and prognostic values of survivin and transforming growth factor beta-1 (TGF-B1) expression in aqueous humor and serum of retinoblastoma (RB) in comparison to the conventional RB marker lactate dehydrogenase (LDH) and to elucidate a possible correlation between them and the clinicopathological features of the disease. Methods This prospective, comparative study included 88 newly diagnosed children with RB and 80 age-matched controls with ophthalmic conditions other than tumors prepared for intraocular surgeries. Concentrations of survivin, TGF-B1, and LDH were measured in serum and aqueous humor before and 6 months after completion of therapy. Results High serum and aqueous humor concentrations of the three proteins were detected in RB patients before treatment compared to the control group ( P P r  = 0.43, P  = 0.04); the best cutoff values of serum and aqueous TGF-B1, 370.7 pg/ml and 39.8 pg/mg, with a significant positive correlation between aqueous TGF-B1 and poor differentiation of the tumor ( r  = 0.69, P  = 0.001). Conclusions The high sensitivity, specificity, and accuracy of serum and aqueous humor survivin and TGF-B1 proteins make them promising markers for early detection and follow-up of RB patients.

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Clinical significance of high levels of survivin and transforming growth factor beta-1 proteins in aqueous humor and serum of retinoblastoma patients.

There is growing biomedical interest in survivin as a diagnostic and prognostic factor in human neoplasms. The present work assessed survivin expression in retinoblastoma. Survivin was quantitatively measured in 82 aqueous humor and serum samples from 41 children with retinoblastoma and nonmalignant ophthalmic diseases. After treatment, 12 serum samples from retinoblastoma patients were included. Survivin levels were higher in aqueous humor and serum of retinoblastoma patients than the controls (P < 0.05). In aqueous, it was significantly correlated with the tumor stage and optic nerve affection. The best cutoff values for survivin in aqueous and serum that differentiate between retinoblastoma and nonmalignant ophthalmic diseases were 25.2 pg/mg protein and 12.9 pg/mL, respectively. The sensitivity and specificity were 100% and 90% in serum and 94% and 48% in aqueous, respectively. Serum survivin has decreased significantly after treatment. Measurement of survivin protein might have a great diagnostic and prognostic potential in retinoblastoma.

Azza Hassan Abou Ghalia

Papers

Glutathione and its metabolizing enzymes in patients with different benign and malignant diseases.

Serum leptin as an additional possible pathogenic factor in polycystic ovary syndrome

Detection of survivin protein in aqueous humor and serum of retinoblastoma patients and its clinical significance.

Clinical significance of high levels of survivin and transforming growth factor beta-1 proteins in aqueous humor and serum of retinoblastoma patients.

Role of Survivin in Retinoblastoma: Diagnosis and Prognosis