Unraveling Hypothalamus-Pituitary dysregulation: Hypergonadotropism in F progeny due to prenatal exposure to hexavalent chromium.

The endocrine disruptor hexavalent chromium [Cr(VI)] is a proven reproductive toxicant. We recently demonstrated that prenatal Cr(VI) exposure causes testicular resistance to gonadotropins, resulting in hypergonadotropic hypoandrogenism in F rats. However, the mechanism driving hypergonadotropism in F rats exposed to Cr(VI) prenatally remains an enigma.

Prenatal exposure to hexavalent chromium disrupts testicular steroidogenic pathway in peripubertal F rats.

We have reported sub-fertility in F progeny rats with gestational exposure to hexavalent chromium [Cr(VI)], which had disrupted Sertoli cell (SC) structure and function, and decreased testosterone (T). However, the underlying mechanism for reduced T remains to be understood. We tested the hypothesis "transient prenatal exposure to Cr(VI) affects testicular steroidogenesis by altering hormone receptors and steroidogenic enzyme proteins in Leydig cells (LCs).

Prenatal exposure to excess chromium attenuates transcription factors regulating expression of androgen and follicle stimulating hormone receptors in Sertoli cells of prepuberal rats.

We have reported that gestational exposure to hexavalent chromium (CrVI) represses androgen receptor (Ar) and follicle stimulating hormone receptor (Fshr) in Sertoli cells (SCs) of adult rats, while the mechanism underlying remains obscure. We tested the hypothesis "transient gestational exposure to CrVI during the critical embryonic windows of testicular differentiation and growth may have adverse impact on transcription factors controlling the expression of Ar and Fshr in SCs of the F progeny". CrVI (KCrO) was given through drinking water (50 ppm, 100 ppm and 200 ppm), to pregnant rats from gestational day 9-14 (testicular differentiation) and 15 to 21 (prenatal differentiation and proliferation of SC); male progenies were sacrificed on postnatal day 30 (Completion of postnatal SC maturation).

Transient gestational exposure to drinking water containing excess hexavalent chromium modifies insulin signaling in liver and skeletal muscle of rat progeny.

Chromium (Cr), an essential micronutrient potentiates insulin action, whereas excess hexavalent Cr (CrVI) acts as an endocrine disruptor. Pregnant mothers living in areas abutting industries using the metal and chromite ore dumps are exposed to ground water contaminated with Cr. Nevertheless, the impact of prenatal exposure to excess CrVI on insulin signaling in the progeny remains obscure.

Male reproductive toxicity of CrVI: In-utero exposure to CrVI at the critical window of testis differentiation represses the expression of Sertoli cell tight junction proteins and hormone receptors in adult F progeny rats.

The effect of gestational exposure to CrVI (occupational/environmental pollutant and target to Sertoli cells(SC)) was tested in a rat model during the testicular differentiation from the bipotential gonad may interrupt spermatogenesis by disrupting SC tight junctions(TJ) and it's proteins and hormone receptors. Pregnant Wistar rats were exposed to 50/100/200ppm CrVI through drinking water during embryonic days 9-14. On Postnatal day 120, testes were subjected to ion exchange chromatographic analysis and revealed increased level of CrIII in SCs and germ cells, serum and testicular interstitial fluid(TIF).

Lipid peroxidation and antioxidants status in human malignant and non-malignant thyroid tumours.

Introduction: Thyroid epithelial cells produce moderate amounts of reactive oxygen species that are physiologically required for thyroid hormone synthesis. Nevertheless, when they are produced in excessive amounts, they may become toxic.

Objective: The present study is aimed to compare the lipid peroxidation (LPO), antioxidant enzymes - superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and non-protein thiols (reduced glutathione (GSH)) in human thyroid tissues with malignant and non-malignant disorders.

Transient gestational and neonatal hypothyroidism-induced specific changes in androgen receptor expression in skeletal and cardiac muscles of adult rat.

The present study aims to identify the association between androgen status and metabolic activity in skeletal and cardiac muscles of adult rats with transient gestational/neonatal-onset hypothyroidism. Pregnant and lactating rats were made hypothyroid by exposing to 0.05% methimazole in drinking water; gestational exposure was from embryonic day 9-14 (group II) or 21 (group III), lactational exposure was from postnatal day 1-14 (group IV) or 29 (group V).

Persistent hexavalent chromium exposure impaired the pubertal development and ovarian histoarchitecture in wistar rat offspring.

Hexavalent chromium (CrVI) is a highly toxic metal and a major environmental pollutant. Several studies indicate that CrVI exposure adversely affects reproductive function. We reported that maternal Cr exposure resulted in Cr accumulation in the reproductive organs of female offsprings.

Regulation of insulin-like growth factors and their binding proteins by thyroid stimulating hormone in human osteoblast-like (SaOS2) cells.

Thyroid stimulating hormone (TSH) is shown to have definite anabolic effects on skeletal metabolism. Previous studies have demonstrated that Insulin-like growth factors (IGF-I and IGF-II) and their six high affinity binding proteins (IGFBPs 1-6) regulate proliferation and differentiation of bone-forming osteoblasts. The current study was intended to determine whether the anabolic effects of TSH on human osteoblastic (SaOS2) cells are mediated through insulin-like growth factor system components.

Androgen receptor expression in human thyroid cancer tissues: a potential mechanism underlying the gender bias in the incidence of thyroid cancers.

Gender bias in the incidence of thyroid cancer is well known, however, the underlying mechanism is largely unknown. The current study determines variations in the molecular characteristics of thyroid cancers between men and women. Normal and cancerous thyroid tissues were collected from a total of 125 men and women who underwent surgical thyroidectomy.

Ameliorative effect of vitamin C on hexavalent chromium-induced delay in sexual maturation and oxidative stress in developing Wistar rat ovary and uterus.

Hexavalent chromium (CrVI) is a highly toxic metal and major environmental pollutant and is extensively used in more than 50 industries. The major route of CrVI exposure for the general population is oral intake. Chromium is considered an important nutrient responsible for carbohydrate metabolism.

Is gender difference in postnatal thyroid growth associated with specific expression patterns of androgen and estrogen receptors?

Variations in sex steroids bioavailability were linked to the gender difference in the growth of thyroid glands of neonatal rats. In the present study we tested androgen receptor (AR) and estrogen receptor (ER) concentrations by ligand binding assay, and expression of their genes by RT-PCR and Western blot in the thyroid glands of neonatal rats. AR concentration remained elevated from postnatal day (PND) 10 onwards in males, whereas it decreased by PND 20 in females.

Mechanism underlying transient gestational-onset hypothyroidism-induced impairment of posttesticular sperm maturation in adult rats.

Objective: To understand the mechanism underlying gestational-onset hypothyroidism-induced male infertility.

Design: Controlled laboratory study.

Setting: Research laboratory in a university department of endocrinology.

Lactational hexavalent chromium exposure-induced oxidative stress in rat uterus is associated with delayed puberty and impaired gonadotropin levels.

Hexavalent chromium (CrVI) is a transition element utilized in many fields of modern industries. CrVI is a reproductive metal toxicant that can traverse the placental barrier and cause a wide range of fetal effects. Therefore, the present study was carried out to determine the CrVI-induced utero-toxicity.

Gestational and neonatal-onset hypothyroidism alters androgen receptor status in rat prostate glands at adulthood.

Background: Infertility associated with congenital and early childhood hypothyroidism is an important reproductive health problem in men. Nevertheless, the exact mechanism underlying hypothyroidism-induced changes in the prostate gland, an androgen-dependent organ that contributes a significant portion of the seminal plasma remains obscure. The present study tested the hypothesis "transient gestational- or neonatal-onset hypothyroidism may have duration dependent and lobe specific effect on androgen receptor (AR) status in the prostate glands of adult rats.

Lactational exposure to hexavalent chromium delays puberty by impairing ovarian development, steroidogenesis and pituitary hormone synthesis in developing Wistar rats.

Hexavalent chromium (Cr-VI) is used in a wide range of industries. Cr-VI from chromate industries and atmospheric emissions contribute to the Cr contamination in the environment. Cr is a reproductive metal toxicant that can traverse the placental barrier and cause a wide range of fetal effects including ovotoxicity.

Protective role of melatonin on PCB (Aroclor 1,254) induced oxidative stress and changes in acetylcholine esterase and membrane bound ATPases in cerebellum, cerebral cortex and hippocampus of adult rat brain.

Polychlorinated biphenyls (PCBs) are one of the environmental toxicants and neurotoxic compounds which induce the production of free radicals leading to oxidative stress. Membrane proteins that control ion gradients across organellar and plasma membranes appear to be particularly susceptible to oxidation induced changes. Melatonin plays an important role in neurodegenerative diseases as an antioxidant and neuroprotector.

Effects of streptozotocin (STZ)-induced diabetes and insulin replacement on rat ventral prostate.

Background: Diabetes mellitus due to insulin deficiency has adverse effect on all organ systems including reproductive organs. Streptozotocin (STZ)-induced diabetes in rats provides a relevant model to study reproductive dysfunction under diabetic conditions, as they exhibit a number of deficits in reproductive function that resemble those seen in humans. The present investigation was designed to delineate the impact of STZ-induced diabetes and insulin replacement on the rat ventral prostate.

Modulation of antioxidant defense system by the environmental fungicide carbendazim in Leydig cells of rats.

Carbendazim (methyl-2-benzimidazole carbamate, MBC) a metabolite of benomyl is one of the most widespread environmental contaminant of major concern to human and animal reproductive health. The present investigation was undertaken to study the impact of carbendazim exposure on Leydig cell functions. Adult albino male rats of the Wistar strain were administered with carbendazim (25 mg/(kg (body weight)/day)) orally for 48 days.

Ameliorative effect of vitamins (alpha-tocopherol and ascorbic acid) on PCB (Aroclor 1254) induced oxidative stress in rat epididymal sperm.

The aim of this study was to investigate the possible protective role of vitamins on PCB (Aroclor 1254)-induced spermiotoxicity using qualitative, quantitative and biochemical approaches. Adult male albino rats of Wistar strain were randomly divided into four groups, each group consists of six animals. The control group received corn oil, the second group of rats were administered Aroclor 1254 at a dose of 2 mg/kg bw/day intraperitoneally for 30 days.

Effect of lycopene on insulin-like growth factor-I, IGF binding protein-3 and IGF type-I receptor in prostate cancer cells.

Purpose: Prostate cancer is the second most common cancer that leads to death in elderly men. The risk of prostate cancer prevalence is often associated with the elevated level of insulin-like growth factor-I (IGF-I) and decreased level of IGF-binding protein 3 (IGFBP-3). Lycopene, a carotenoid, reduces the proliferation of cancer cells and induces apoptosis.

Effects of streptozotocin-induced diabetes mellitus on some bone turnover markers in the vertebrae of ovary-intact and ovariectomized adult rats.

Diabetes mellitus and estrogen deficit are known causes of osteopenia in animal models as well as in humans. In the present work, the combined effect of ovariectomy and diabetes was investigated. Diabetes was induced in ovary-intact and ovariectomized female Wistar rats with a single injection (50 mg/kg body weight, i.

PCB (Aroclor 1254) enhances oxidative damage in rat brain regions: protective role of ascorbic acid.

PCBs are one of the environmental toxicants and neurotoxic compounds which induce the production of free radicals leading to oxidative stress. Oxidative stress is a contributing factor to alteration caused in neurodegenerative processes. The ability of Vitamin C to retard oxidative processes has been recognized for many years.

Effect of 17beta-estradiol on apoptosis, IGF system components and gelatinases A and B in prostate cancer cells (PC-3).

Background: Previous studies have indicated that estrogen administration in the advanced stage of prostate cancer provide some benefits to the patients. Estrogen action was thought to be mediated via the blockade of the pituitary-testicular axis that effectively lowered the circulating levels of androgen and, thus, results in tumor regression; however, the effect of estrogens on prostate epithelial cells is still unclear. We investigated the effects of estradiol on insulin-like growth factor type I receptor (IGF-IR), IGF-binding protein 3 (IGFBP-3), IGFBP-4, and matrix metalloproteinase 2 (MMP-2) and MMP-9 in androgen-independent prostate cancer cells (PC-3).