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Hormone Synthesis (hormone + synthesis)
Selected AbstractsChanges in expression and activity levels of ecto-5,-nucleotidase/CD73 along the mouse female estrous cycleACTA PHYSIOLOGICA, Issue 2 2010E. Aliagas Abstract Aim:, Extracellular ATP and its hydrolysis product adenosine modulate various reproductive functions such as those requiring contraction, hormone synthesis and maintenance of fluid composition. Moreover, adenosine is a key molecule for sperm capacitation. Extracellular nucleotide and nucleoside levels are affected by cell surface ectonucleotidases, amongst which the ectonucleoside triphosphate diphosphohydrolase (E-NTPDase) family is the most abundant and effective to hydrolyse ATP and ADP to AMP. In the female reproductive tract three members of this family have been recently identified: NTPDase1, NTPDase2 and NTPDase3 (Histochem. Cell Biol.131, 2009, 615). The purpose of the present study was to characterize in this system the expression profile of ecto-5,-nucleotidase (CD73), the enzyme generating adenosine from AMP. Methods:, Immunological techniques and in situ enzymatic assays were used to characterize the ecto-5,-nucleotidase expression in the mouse female reproductive tract along the four stages of the estrous cycle, that were determined by vaginal smear examination. Results:, Ecto-5,-nucleotidase was abundantly detected in the corpora lutea of the ovaries, as well as in several epithelia, such as that of oviducts, uterus and endometrial glands. Marked changes in endometrial ecto-5,-nucleotidase expression and activity along the estrous cycle are described, these being maximum at estrus phase, coinciding with optimal female sexual receptivity. Conclusion:, The adenosine generated thereby, besides other functions, might contribute to sperm capacitation, thus significantly influencing fertility. [source] Synergistic interaction of endocrine-disrupting chemicals: Model development using an ecdysone receptor antagonist and a hormone synthesis inhibitorENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 4 2004Xueyan Mu Abstract Endocrine toxicants can interfere with hormone signaling through various mechanisms. Some of these mechanisms are interrelated in a manner that might result in synergistic interactions. Here we tested the hypothesis that combined exposure to chemicals that inhibit hormone synthesis and that function as hormone receptor antagonists would result in greater-than-additive toxicity. This hypothesis was tested by assessing the effects of the ecdysteroid-synthesis inhibitor fenarimol and the ecdysteroid receptor antagonist testosterone on ecdysteroid-regulated development in the crustacean Daphnia magna. Both compounds were individually characterized for effects on the development of isolated embryos. Fenarimol caused late developmental abnormalities, consistent with its effect on offspring-derived ecdysone in the maturing embryo. Testosterone interfered with both early and late development of embryos, consistent with its ability to inhibit ecdysone provided by maternal transfer (responsible for early developmental events) or de novo ecdysone synthesis (responsible for late developmental events). We predicted that, by decreasing endogenous levels of hormone, fenarimol would enhance the likelihood of testosterone binding to and inhibiting the ecdysone receptor. Indeed, fenarimol enhanced the toxicity of testosterone, while testosterone had no effect on the toxicity of fenarimol. Algorithms were developed to predict the toxicity of combinations of these two compounds based on independent joint action (IJA) alone as well as IJA with fenarimol-on-testosterone synergy (IJA+SYN). The IJA+SYN model was highly predictive of the experimentally determined combined effects of the two compounds. These results demonstrate that some endocrine toxicants can synergize, and this synergy can be accurately predicted. [source] Analysis of cell signalling in the rodent pineal gland deciphers regulators of dynamic transcription in neural/endocrine cells,EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2001Jörg H. Stehle Abstract In neurons, a temporally restricted expression of cAMP-inducible genes is part of many developmental and adaptive processes. To understand such dynamics, the neuroendocrine rodent pineal gland provides an excellent model system as it has a clearly defined input, the neurotransmitter norepinephrine, and a measurable output, the hormone melatonin. In this system, a regulatory scenario has been deciphered, wherein cAMP-inducible genes are rapidly activated via the transcription factor phosphoCREB to induce transcriptional events necessary for an increase in hormone synthesis. However, among the activated genes is also the inhibitory transcription factor ICER. The increasing amount in ICER protein leads ultimately to the termination of mRNA accumulation of cAMP-inducible genes, including the gene for the Aa-nat that controls melatonin production. This shift in ratio of phosphoCREB and ICER levels that depends on the duration of stimulation can be interpreted as a self-restriction of cellular responses in neurons and has also been demonstrated to interfere with cellular plasticity in many non-neuronal systems. [source] Structure, regulation and evolution of Nox-family NADPH oxidases that produce reactive oxygen speciesFEBS JOURNAL, Issue 13 2008Hideki Sumimoto NADPH oxidases of the Nox family exist in various supergroups of eukaryotes but not in prokaryotes, and play crucial roles in a variety of biological processes, such as host defense, signal transduction, and hormone synthesis. In conjunction with NADPH oxidation, Nox enzymes reduce molecular oxygen to superoxide as a primary product, and this is further converted to various reactive oxygen species. The electron-transferring system in Nox is composed of the C-terminal cytoplasmic region homologous to the prokaryotic (and organelle) enzyme ferredoxin reductase and the N-terminal six transmembrane segments containing two hemes, a structure similar to that of cytochrome b of the mitochondrial bc1 complex. During the course of eukaryote evolution, Nox enzymes have developed regulatory mechanisms, depending on their functions, by inserting a regulatory domain (or motif) into their own sequences or by obtaining a tightly associated protein as a regulatory subunit. For example, one to four Ca2+ -binding EF-hand motifs are present at the N-termini in several subfamilies, such as the respiratory burst oxidase homolog (Rboh) subfamily in land plants (the supergroup Plantae), the NoxC subfamily in social amoebae (the Amoebozoa), and the Nox5 and dual oxidase (Duox) subfamilies in animals (the Opisthokonta), whereas an SH3 domain is inserted into the ferredoxin,NADP+ reductase region of two Nox enzymes in Naegleria gruberi, a unicellular organism that belongs to the supergroup Excavata. Members of the Nox1,4 subfamily in animals form a stable heterodimer with the membrane protein p22phox, which functions as a docking site for the SH3 domain-containing regulatory proteins p47phox, p67phox, and p40phox; the small GTPase Rac binds to p67phox (or its homologous protein), which serves as a switch for Nox activation. Similarly, Rac activates the fungal NoxA via binding to the p67phox -like protein Nox regulator (NoxR). In plants, on the other hand, this GTPase directly interacts with the N-terminus of Rboh, leading to superoxide production. Here I describe the regulation of Nox-family oxidases on the basis of three-dimensional structures and evolutionary conservation. [source] Identification of the rat adrenal zona fasciculata/reticularis specific protein, inner zone antigen (IZAg), as the putative membrane progesterone receptorFEBS JOURNAL, Issue 7 2001Farah S. Raza Using immunological methods, a protein specific to the inner zones of the rat adrenal cortex, and called inner zone antigen (IZAg), was previously shown to have two interrelated forms of 26 kDa (IZAg1) and 55,60 kDa (IZAg2), and to have an action on steroid hydroxylation. After two-dimensional gel electrophoresis, and immunoaffinity column purification, N-terminal amino-acid analysis showed that the first 12 amino acids were identical to those of a recently described putative membrane located progesterone receptor (PPMR). RT-PCR was then used to generate the cDNA of this protein, using RNA extracted from rat adrenals. A glutathione S-transferase (GST)-fusion construct was expressed in Escherichia coli, and shown to generate an immunoreactive product of molecular mass consistent with its identification as IZAg1. More detailed examination of the distribution of this protein, not only in the zona fasciculata/reticularis of the adrenal cortex, but also in the Leydig cell, kidney and liver, suggest it may have a role in steroid hormone synthesis and/or metabolism. [source] Estimation of number of follicles, volume of colloid and inner follicular surface area in the thyroid gland of ratsJOURNAL OF ANATOMY, Issue 2 2005M. L. Hartoft-Nielsen Abstract Volume is an important variable in assessing the growth and involution of the thyroid gland. The functional unit in the thyroid is the follicle, which consists of thyrocytes surrounding colloid. The size of a follicle depends on the number of cells and the amount of colloid. These are interchangeable and vary according to biological activity. Direct measurements of these variables provide information on structures involved in thyroid hormone synthesis, storage and secretion, and also on changes at the morphological and functional levels. Stereological methods are developed to obtain information on three-dimensional structures from two-dimensional sections and to achieve information on an entire organ by examining a minor part of it. Full-grown male Sprague,Dawley rats were used to develop a set of methods relying on unbiased stereological principles to determine the number of follicles, the total volume of colloid and the inner follicular surface area in the thyroid gland. The total volume of colloid was positively correlated (P < 0.021) with the number of follicles and the inner follicular surface area (P < 0.002) but not to the mean volume of colloid in each follicle. Thus under physiological conditions an increase in the total volume of colloid is associated with an increased number of follicles with a constant size distribution rather than a larger volume of colloid in each follicle. This implies that under physiological conditions there is equilibrium in the size distribution of the volume of colloid in each follicle. [source] Hypothalamic Control of Anterior Pituitary Function: A HistoryJOURNAL OF NEUROENDOCRINOLOGY, Issue 6 2008H. Charlton The concept of neurohumoral control of anterior pituitary function championed by Geoffrey Harris was based upon clinical and biological observation backed by rigorous experimental testing. The areas of the brain involved in the control of gonadotrophic hormone synthesis and release were identified by electrical stimulation, lesioning and fibre tract cutting. The medial preoptic area (MPOA) proved to be a major integrating centre, with axon terminals from this region terminating at the median eminence releasing factors into the portal vessels to give a direct route from brain to pituitary. It took over a decade before the gonadotrophic hormone-releasing hormone (GnRH) was isolated, sequenced and synthesised. With antibodies raised against this peptide, the MPOA was identified as a site rich in GnRH neurones and the hormone was detected at high levels in portal blood extracts. A natural knockout of the GnRH gene was discovered in a hypogonadal (hpg) mouse. Hormone injections, gene replacement methods and neural grafting in these mutants all confirmed the central role of GnRH in reproduction. The modern techniques of molecular biology have allowed us to extend our knowledge base. In the last few years the role of kisspeptin and its receptor (GPR54) in the control of the GnRH neurone has added a further level of hypothalamic involvement in the modulation of reproduction. [source] White Adipose Tissue: Getting NervousJOURNAL OF NEUROENDOCRINOLOGY, Issue 11 2003E. Fliers Abstract Neuroendocrine research has altered the traditional perspective of white adipose tissue (WAT) as a passive store of triglycerides. In addition to fatty acids, WAT produces many hormones and can therefore be designated as a traditional endocrine gland actively participating in the integrative physiology of fuel and energy metabolism, eating behaviour and the regulation of hormone secretion and sensitivity. WAT is controlled by humoral factors, para- and intracrine factors and by neural regulation. Sympathetic nerve fibres innervate WAT and stimulate lipolysis, leading to the release of glycerol and free fatty acids. In addition, recent research in rats has clearly shown a functional parasympathetic innervation of WAT. There appears to be a distinct somatotopy within the parasympathetic nuclei: separate sets of autonomic neurones in the brain stem innervate either the visceral or the subcutaneous fat compartment. We therefore propose that the central nervous system (CNS) plays a major role in the hitherto unexplained regulation of body fat distribution. Parasympathectomy induces insulin resistance with respect to glucose and fatty acid uptake in the innervated fat depot and has selective effects on local hormone synthesis. Thus, the CNS is involved not only in the regulation of hormone production by WAT, but also in its hormone sensitivity. The developments in this research area are likely to increase our insights in the pathogenesis of metabolic disorders such as hypertriglyceridemia, diabetes mellitus type 2 and lipodystrophy syndromes. [source] Short-Term Antiandrogen Flutamide Treatment Causes Structural Alterations in Somatic Cells Associated with Premature Detachment of Spermatids in the Testis of Pubertal and Adult Guinea PigsREPRODUCTION IN DOMESTIC ANIMALS, Issue 3 2010LR Maschio Contents In spite of widespread application of flutamide in the endocrine therapies of young and adult patients, the side effects of this antiandrogen on spermatogenesis and germ-cell morphology remain unclear. This study evaluates the short-term androgen blockage effect induced by the administration of flutamide to the testes of pubertal (30-day old) and adult (65- and 135-day old) guinea pigs, with an emphasis on ultrastructural alterations of main cell types. The testes removed after 10 days of treatment with either a non-steroidal antiandrogen, flutamide (10 mg/kg of body weight) or a pharmacological vehicle alone were processed for histological, quantitative and ultrastructural analysis. In pubertal animals, flutamide androgenic blockage induces spermatogonial differentiation and accelerates testes maturation, causing degeneration and detachment of primary spermatocytes and round spermatids, which are subsequently found in great quantities in the epididymis caput. In post-pubertal and adult guinea pigs, in addition to causing germ-cell degeneration, especially in primary spermatocytes, and leading to the premature detachment of spherical spermatids, the antiandrogen treatment increased the relative volume of Leydig cells. In addition, ultrastructural evaluation indicated that irrespective of age antiandrogen treatment causes an increase in frequency of organelles involved with steroid hormone synthesis in the Leydig cells and a dramatic accumulation of myelin figures in their cytoplasm and, to a larger degree, in Sertoli cells. In conclusion, the transient exposition of the guinea pigs to flutamide, at all postnatal ages causes some degenerative lesions including severe premature detachment of spermatids and accumulation of myelin bodies in Leydig and Sertoli cells, compromising, at least temporarily, the spermatogenesis. [source] Thiocyanate overload and thyroid diseaseBIOFACTORS, Issue 3-4 2003Murat Faik Erdo Abstract Thiocyanate [SCN,] is a complex anion which is a potent inhibitor of iodide transport. It is the detoxification product of cyanide and can easily be measured in body fluids. Consumption of naturally occurring goitrogens, certain environmental toxins and cigarette smoke can significantly increase SCN, concentrations to levels potentially capable of affecting the thyroid gland. Goiter endemics were reported to develop when the critical urinary iodine/ SCN, ratio decreases below 3 ,g iodine per mg SCN,. Iodine supplementation completely reverses the goitrogenic influence of SCN,. SCN, is also generated from cigarette smoking as a detoxifying product of cyanide. During the past two decades many reports dealt with the possible effects of cigarette smoking on thyroid hormone synthesis, thyroid gland size and thyroid autoimmunity including infiltrative ophtalmopathy of Graves' disease. In this mini-review, issues regarding thiocyanate overload and thyroid disease will be summarized. [source] Flavonoids and thyroid diseaseBIOFACTORS, Issue 3-4 2003Daan Van Der Heide Abstract The most potent natural plant-derived compounds that can affect thyroid function, thyroid hormone secretion and availability to tissues is the group of flavonoids, i.e. plant pigments. They are present in our daily food, such as vegetables, fruits, grains, nuts, wine, and tea. Epidemiological studies suggest beneficial effects on health of flavonoids, which are commonly attributed to their activity as antioxidants. Experimental studies in vitro, however, showed inhibition of organification in thyroid cells and follicles by several flavonoids. Studies in vivo and vitro with synthetic and natural flavonoids showed displacement of T4 from transthyretin leading to disturbances in thyroid hormone availability in tissues. Radioactive labeled flavonoids appeared to be eliminated rapidly from the body mainly through excretion in the feces. In pregnant rats synthetic flavonoids cross the placenta and accumulate in the fetal compartment, including the fetal brain. Therefore, a high intake of flavonoids is contraindicated. In conclusion: flavonoids show strong interference with many aspects of thyroid hormone synthesis and availability. [source] | |||||||||||||