Hormonal status of male reproductive system: androgens and estrogens in the testis and epididymis. In vivo and in vitro approaches

The purpose of this article was to summarize our results on the role of androgens and estrogens in human, rodent and equine testes and epididymides, in both, physiological and patological conditions, obtained in the space of the Solicited Project (084/PO6/2002) financially supported by the State Committee for Scientific Research during the last three years. Testosterone produced by Leydig cells of the testes is clearly the major androgen in the circulation of men and adult males of most mammalian species. However, androgen metabolites make up a significant fraction of total circulating steroids. Moreover, androgen metabolism may proceed to amplify the action of testosterone through its conversion to dihydrotestosterone (DHT) or its aromatization to estradiol. The distribution of androgen and estrogen receptors (ARs and ERs) within male reproductive tissues is important because of their crucial role in mediating androgen and/or estrogen action. Attempts were undertaken to discuss not only the role of aromatase and ERs in mediating the action of estrogens in the male, but also the importance of DHT in hormonal regulation of the epididymis. In the latter, alterations caused by finasteride treatment and lead-induced oxidative stress are described. Male reproductive function of the testis and epididymis reflected by the alterations in enzymatic activity, distribution of steroid hormone receptors, differences in steroid hormone levels and altered gene expression of antioxidant enzymes are also discussed.     

The influence of polychlorinated biphenyls (PCBs) and phytoestrogens in vitro on functioning of reproductive tract in cow

Ovarian, endometrial and myometrial cells and strips of longitudinal myometrium from cows on defined days of estrous cycle were treated for 24-72 h with different doses (1-100 ng/ml) of PCBs mixture (Aroclor 1248) or with one of PCB congeners (126, 77, 153). The administered doses of PCBs neither affected the viability of cells nor influenced the ovarian steroidogenesis as measured by progesterone (P(4)), estradiol (E(2)) and testosterone secretion from luteal, granulosa and theca cells, respectively. In contrast, PCBs clearly inhibited a FSH and LH-stimulated effect on steroids secretion from granulosa and luteal cells. Moreover, PCBs significantly stimulated oxytocin (OT) secretion from the studied ovarian cells, and at least part of this effect is elicited through activation of glucocorticoid receptors. Further, PCBs were found to increase basal intracellular concentrations of Ca(2+) and both spontaneous and OT-stimulated contractions of myometrial strips. Concomitantly, PCBs increased endometrial secretion of PGF(2alpha), hence the ratio of PGF(2alpha):PGE(2) was also increased. Phytoestrogens (genistein, daidzein, coumestrol), with a different intensity, reduced the effect of PCBs on PGF(2alpha) secretion and myometrial contractions. Genistein inhibited PCBs' effect on OT secretion from granulosa cells, while PCB's effect on OT release from luteal cells was reduced mainly by genistein and daidzein. We conclude that PCBs can impair both ovarian functioning and uterine contractility, while phytoestrogens are able to reduce this effect.     

Increased Reactive Oxygen Species Production in the Brain After Repeated Low-Dose Pesticide Paraquat Exposure in Rats. A Comparison with Peripheral Tissues

The pesticide paraquat (PQ) was found to be a suitable xenobiotic to model Parkinson’s disease. The reactive oxygen species (ROS) production was suggested to be the main cause of PQ toxicity but very few evidences were found for its generation in the brain in vivo after ip administration. We compared the effects of PQ-induced ROS generation between the brain structures and the peripheral tissues using two different hydroxyl radical generation markers. Repeated but not single ip PQ administration increased the levels of ROS in the striatal homogenates but, when measured in the extracellular microdialysis filtrate, no change was observed. The increased dopamine release was detected in the striatum after the fourth PQ administration and its basal levels were decreased. A single treatment with the pesticide did not influence ROS production in the lungs or kidneys but repeated intoxication decreased its levels. These results suggest that repeated, systemic administration of a low dose of PQ triggers intracellular ROS formation in the brain and can cause slowly progressing degenerative processes, without the toxic effects in the peripheral tissues.     

Can inhibition of angiogenesis and stimulation of immune response be combined into a more effective antitumor therapy?

Cancer initiation and progression is strongly influenced by the tumor microenvironment consisting of various types of host cells (inflammatory cells, vascular cells and fibroblasts), extracellular matrix and non-matrix molecules. Host cells play a defining role in two major processes crucial for tumor growth: angiogenesis and escape from immune surveillance. The interdependence of these processes resemble the principles of Yin and Yang, as the stimulation of tumor angiogenesis inhibits effective immune responses, while angiogenesis inhibition may have the opposite effect. These considerations may be useful in developing anticancer strategies based on the potentially synergistic combinations of antiangiogenic and immunostimulatory drugs.     

The diagnostic value of thyroglobulin concentration in fine-needle aspiration of the cervical lymph nodes in patients with differentiated thyroid cancer

INTRODUCTION: Recurrent differentiated thyroid cancer generally occurs first in the neck. Ultrasound is sensitive in detecting enlarged cervical lymph nodes but is not specific enough. Ultrasound-guided fine-needle biopsy increases the specificity but still may fail to detect a recurrence of the disease in the cystic metastatic lymph nodes. The aim of the study was to estimate the value of Tg concentration in the needle washout after fine-needle aspiration of suspicious lymph nodes. MATERIAL AND METHODS: The 105 patients studied had presented one or more enlarged suspicious cervical lymph nodes. All had undergone total thyroidectomy and (131)I ablative therapy. Serum thyroglobulin (Tg) concentration was within the 0.15-711.5 ng/ml range (mean 22.24 ng/ml) and Tg recovery range 94-100%. The positive Tg washout concentration cut-off value was established as equal to the mean plus two standard deviations of the Tg washout concentration of patients with negative cytology. RESULTS: Lymph node involvement was diagnosed by cytology in 15 patients and in 28 lymph nodes. Positive Tg washout concentration was found in 22 patients and in 48 lymph nodes. All the lymph nodes which turned out to have positive cytology had a positive Tg washout concentration. All lymph nodes with positive cytology were positive in pathology. Seven patients and 20 lymph nodes with negative cytology were positive in the Tg washout concentration test. All but one patients and all but two lymph nodes with a positive Tg washout concentration had positive pathology. CONCLUSIONS: 1. Ultrasound-guided fine-needle biopsy is not sensitive enough to detect all metastatic lymph nodes. 2. The Tg washout concentration test is 100% sensitive in the detection of metastatic lymph nodes. 3. Cytology in ultrasound- guided fine-needle biopsy is 100% specific. 4. The Tg washout concentration test carries a risk of false-positive results. 5. Both methods should be used for early detection of metastatic lymph nodes in patients with differentiated thyroid cancer.     

The effects of melatonin, N-acetylserotonin, and 6-hydroxymelatonin on the ultrastructure of the pinealocytes of the Syrian hamster (Mesocricetus auratus)

OBJECTIVES: The aim of this study was to examine the effects of melatonin as well as of its precursor (N-acetylserotonin) and metabolite (6-hydroxymelatonin) on the ultrastructure of the pinealocytes of the Syrian hamster. MATERIAL AND METHODS: The pineal glands of 2-month-old male Syrian hamsters were examined. The animals were divided into the following groups of four animals each: group 1 - melatonin treatment; group 2 - N-acetylserotonin treatment; group 3 - 6-hydroxymelatonin treatment (all substances given subcutaneously at doses of 25 microg per animal between 16.00 and 17.00 h daily for seven weeks). Group 4 was given solvent treatment only and served as controls. The animals were killed by decapitation between 09:00 and 10.00 h. Routine electron microscopical techniques were used to obtain quantitative data on pinealocyte ultrastructure. RESULTS: Melatonin administration did not influence the size of the hamster pinealocytes, whereas administration of N-acetylserotonin and 6-hydroxymelatonin caused a significant reduction in cell size in comparison to the melatonin-treated and control groups. There were changes in the relative volumes of the mitochondria, Golgi apparatus and lysosomes in the pinealocytes of the studied groups, while the volumes of granular endoplasmic reticulum and lipid droplets were unchanged. The dense-core vesicles were more numerous in the pinealocytes of the melatonin and 6-hydroxymelatonin-treated groups in comparison to those of animals treated with N-acetylserotonin or the controls. CONCLUSIONS: The changes observed in the ultrastructure of hamster pinealocytes indicate that administration of melatonin as well as of its precursor or metabolite influences the morphology of these cells and also, perhaps, their secretory activity.     

Hyperprolactinemia: causes, diagnosis, and treatment

The basic data on hyperprolactinemia (i.e. an excess of PRL above a reference laboratory's upper limits), the most common endocrine disorder of the hypothalamic-pituitary axis are given in this review. The following issues are discussed: regulation of prolactin (Prl) secretion, definition of hyperprolactinemia, its etiology and pathogenesis as well as its symptoms, diagnosis, and treatment (including medical and surgical therapy). It should be stressed that finding of elevated PRL serum concentrations constitute the beginning of diagnostic procedure and, after exclusion of physiologic, pharmacologic, and other organic causes of increased PRL levels, should be followed by detailed diagnosis including MRI. In patients in whom hyperprolactinemia has been confirmed the treatment with dopamine agonists (with prevalence of cabergoline, followed by quinagoline) is currently considered first-choice therapy. Surgery should be performed only in the patients resistant or intolerant to these agents, or in patients who refuse long-term therapy.