Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.14.16.2 (tyrosine hydroxylase)
 14,760 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gonadal steroids exert a powerful regulatory influence upon the functioning of gonadotropin-releasing hormone (GnRH) neurons despite the apparent absence of gonadal steroid receptors in these cells. By using retrograde-tracing techniques combined with dual-labeling immunocytochemistry, we show here that distinct populations of estrogen receptor alpha (ERalpha)-containing neurons located in the hypothalamus and caudal brainstem project to the vicinity of the GnRH perikarya located in the rostral preoptic area (rPOA). The strongest estrogen-receptive afferent projection to this area originated from neurons located in the anteroventral periventricular and medial preoptic nuclei of the preoptic area. Approximately 50% of arcuate nucleus neurons projecting to the rPOA were demonstrated to synthesize either neuropeptide Y or beta-endorphin, but little evidence was found for ERalpha immunoreactivity in either of these specific subpopulations. Over 80% of all tyrosine hydroxylase-expressing neurons in the arcuate nucleus expressed ERalpha, but none projected to the rPOA. In the caudal brainstem, the A1 and A2 norepinephrine neurons comprised nearly all of the retrogradely labeled neurons. However, only the A2 afferents expressed ERalpha immunoreactivity, whereas the A1 afferents coexpressed neuropeptide Y. These observations, combined with the anterograde labeling data of others, provide neuroanatomical evidence for the existence of specific estrogen-receptive neuronal cell populations that project to the rPOA and may be involved in the estrogen-dependent transsynaptic regulation of GnRH neurons in the rat.
 ...
PMID:Identification and characterization of estrogen receptor alpha-containing neurons projecting to the vicinity of the gonadotropin-releasing hormone perikarya in the rostral preoptic area of the rat. 1040 58

Estrogen-dependent enhancement of glucoprivic-induced luteinizing hormone (LH) suppression is hypothesized to be due to increased estrogen receptor alpha (ERalpha)-immunoreactive (ir) cells in specific brain nuclei in a manner similar to fasting. ERalpha expression in various brain areas was determined in ovariectomized rats after systemic 2-deoxy-D-glucose (2DG)-induced glucoprivation. Expression of ERalpha in catecholaminergic neurons in the lower brainstem was also examined. ERalpha-ir cells increased in hypothalamic paraventricular and periventricular nuclei, and A1 and A2 regions of the brainstem 1 h after 2DG injection. The percentage of ERalpha in the tyrosine hydroxylase (TH)- and dopamine-beta-hydroxylase (DBH)-ir neurons was higher in A1 and A2 regions of 2DG-treated rats, but the number of TH- and DBH-ir cells did not change. Thus, 2DG induces ERalpha expression in specific brain nuclei and expression of ERalpha in catecholaminergic neurons of the brainstem indicates a role for estrogen in activating those neurons projecting to the hypothalamic paraventricular nucleus to suppress LH secretion during glucoprivation.
 ...
PMID:Glucoprivation increases estrogen receptor alpha immunoreactivity in the brain catecholaminergic neurons in ovariectomized rats. 1116 50

Gender-specific differences in susceptibility to a number of disorders related to catecholaminergic systems, including depression and hypertension, have been postulated to be mediated, at least in part, by estrogens. In this study, we examined if estrogens may regulate gene expression of norepinephrine biosynthetic enzymes. Administration of five injections of 15 or 40 microg/kg estradiol benzoate to ovariectomized (OVX) female rats elicited a dose-dependent elevation in mRNA levels of tyrosine hydroxylase (TH) in locus coeruleus, to as great as 3-fold over control. Dopamine beta-hydroxylase (DBH) mRNA levels were also similarly increased. To examine the mechanism, PC12 cells were cotransfected with luciferase reporter constructs under control of DBH or TH promoters [pDBH/Luc(-2,236/+21) or pTH/Luc(-272/+27 or -773/+27)] with an expression vector for estradiol receptor alpha. The cells were treated with 17beta-estradiol (E(2)) for 12-36 h. E(2) triggered a several fold increase in luciferase activity under control of the DBH promoter in a dose-dependent fashion. Omission of estrogen receptor alpha or addition of the estrogen receptor antagonist ICI 182,780 prevented the DBH promoter-driven increase in luciferase. When E(2) was given with 0.2 mM CPT-cAMP, reporter activity with pDBH/Luc(-2,236/+21) was increased greater than with either treatment alone. In contrast, addition of E(2) to cells transfected with pTH/Luc(-272/+27) elicited no change in basal luciferase activity nor in the response to 0.2 mM CPT-cAMP. These findings are the first to reveal that estrogen can stimulate DBH gene expression. Differing mechanisms may underlie the regulation of TH and DBH gene expression by estrogens.
 ...
PMID:Estradiol stimulates gene expression of norepinephrine biosynthetic enzymes in rat locus coeruleus. 1191 91

Recent evidence suggests that the ovine premammillary hypothalamic area (PMH) is an important target for the pineal hormone, melatonin, and its role in seasonal reproduction. In rodents, the PMH is a complex region consisting of several cell groups with differing neurochemical content and anatomical connections. Therefore, to obtain a better understanding of the potential neural targets for melatonin in this area of the sheep brain, we have undertaken a detailed anatomical characterization of the PMH, including its nuclear divisions and the location of neuropeptide/neurotransmitter cells within them. By combining immunocytochemistry for NeuN, a neuronal marker, with Nissl staining in anestrous, ovariectomized, estradiol-treated ewes, we identified three nuclei within the PMH: a caudal continuation of the hypothalamic arcuate nucleus (cARC), the ventral division of the premammillary nucleus (PMv), and the ventral tuberomammillary nucleus (TMv). The cARC contained neurons that were immunoreactive for tyrosine hydroxylase, dynorphin, estrogen receptor alpha, cocaine- and amphetamine-regulated transcript peptide (CART), and nitric oxide synthase (NOS). The PMv was also characterized by the presence of cells that contained NOS and CART, although the size of these cells was larger than that of their corresponding phenotype in the cARC. By contrast, in the TMv, of the markers examined in the present study, only fibers immunoreactive for orexin were seen. Thus, the ovine PMH is a heterogeneous region comprised of three subdivisions, each with distinct morphological and neurochemical characteristics. This anatomical map of the PMH provides a basis for future studies to determine the functional contribution of each component to the influence of melatonin on seasonal reproduction.
 ...
PMID:The premammillary hypothalamic area of the ewe: anatomical characterization of a melatonin target area mediating seasonal reproduction. 1497 62

Birdsong is a species-typical stereotypic vocalization produced in the context of reproduction and aggression. Among temperate-zone songbirds, it is produced primarily by males, and its frequency and quality are enhanced by the presence of the gonadal steroid hormone testosterone in the plasma. In the brain, the effects of testosterone on song behavior involve both estrogenic and androgenic metabolites of testosterone that are locally produced and act via their cognate receptors. Androgen, and in some cases estrogen, receptors are present in many specialized forebrain song control nuclei. Testosterone can regulate catecholamine steady-state levels and turnover in these song control regions. Tracing studies combined with immunocytochemistry for tyrosine hydroxylase (a marker of catecholamine synthesis) reveal several catecholamine cell groups that project to forebrain song control nuclei. These brain areas also express the mRNA for either androgen receptors or estrogen receptor alpha, and androgens enhance the expression of tyrosine hydroxylase. Dopaminergic cell groups that project to song nuclei express the protein product of the immediate early gene fos in association with the production of territorial song. Thus, testosterone may be acting on song behavior via these ascending catecholamine cell groups. Chemical lesioning studies suggest that noradrenergic projections to the song system are involved in the latency to produce song and the ability to discriminate conspecific from heterospecific song. The song control circuit may thus be modulated in significant ways via the androgen regulation of forebrain catecholamine systems.
 ...
PMID:The activation of birdsong by testosterone: multiple sites of action and role of ascending catecholamine projections. 1499 55

Regulation of gene expression is necessary to avoid possible adverse effects of gene therapy due to excess synthesis of transgene products. To reduce transgene expression, we developed a viral vector-mediated somatic regulation system using inducible Cre recombinase. A recombinant adeno-associated virus (AAV) vector expressing Cre recombinase fused to a mutated ligand-binding domain of the estrogen receptor alpha (CreER(T2)) was delivered along with AAV vectors expressing dopamine-synthesizing enzymes to rats of a Parkinson disease model. Treatment with 4-hydroxytamoxifen, a synthetic estrogen receptor modulator, activated Cre recombinase within the transduced neurons and induced selective excision of the tyrosine hydroxylase (TH) coding sequence flanked by loxP sites, leading to a reduction in transgene-mediated dopamine synthesis. Using this strategy, aromatic L-amino acid decarboxylase (AADC) activity was retained so that l-3,4-dihydroxyphenylalanine (L-dopa), a substrate for AADC, could be converted to dopamine in the striatum and the therapeutic effects of L-dopa preserved, even after reduction of TH expression in the case of dopamine overproduction. Our data demonstrate that viral vector-mediated inducible Cre recombinase can serve as an in vivo molecular switch, allowing spatial and temporal control of transgene expression, thereby potentially increasing the safety of gene therapy.
 ...
PMID:Viral-mediated temporally controlled dopamine production in a rat model of Parkinson disease. 1618 9

There is growing concern that naturally occurring and chemically manufactured endocrine-active compounds (EACs) may disrupt hormone-dependent events during central nervous system development. We examined whether postnatal exposure to the phytoestrogen genistein (GEN) or the plastics component bisphenol-A (BIS) affected sexual differentiation of the anteroventral periventricular nucleus of the hypothalamus (AVPV) in rats. The AVPV is sexually differentiated in rodents. The female AVPV is larger than the male AVPV and contains a higher number of cells expressing tyrosine hydroxylase (TH). Sexual differentiation of the AVPV results from exposure of the male nervous system to estrogen aromatized from testicular testosterone secreted in the first few days after birth. Thus, we hypothesized that exposure to EACs during this critical period could alter the sexually dimorphic expression of TH and the overall expression of estrogen receptor alpha (ERalpha) in the AVPV. Animals were given 4 subcutaneous injections of sesame oil (control), 50 microg 17beta-estradiol (E2), 250 microg GEN, or 250 microg BIS at 12-h intervals over postnatal days (PND) 1 and 2 and sacrificed on PND 19. E2 treatment masculinized TH immunoreactivity (TH-ir) in the female AVPV while exposure to GEN or BIS demasculinized TH-ir in the male AVPV. In addition, we identified a population of neurons co-expressing TH and ERalpha located primarily in the medial region of the AVPV. Normally, females have nearly three times as many double-labeled cells as males, but their numbers were defeminized by E2, GEN or BIS treatment. These results suggest that acute exposure to EACs during a critical developmental period alters AVPV development.
 ...
PMID:Neonatal genistein or bisphenol-A exposure alters sexual differentiation of the AVPV. 1642 66

We hypothesize that estrogen exerts a modulatory effect on sympathetic neurons to reduce neural cardiovascular tone and that these effects are modulated by nerve growth factor (NGF), a neurotrophin that regulates sympathetic neuron survival and maintenance. We examined the effects of estrogen on NGF and tyrosine hydroxylase (TH) protein content in specific vascular targets. Ovariectomized, adult Sprague-Dawley rats were implanted with placebo or 17beta-estradiol (release rate, 0.05 mg/day). Fourteen days later, NGF levels in the superior cervical ganglia (SCG) and its targets, the heart, external carotid artery, and the extracerebral blood vessels, as well as estrogen receptor alpha (ERalpha) content levels in the heart, were determined using semi-quantitative Western blot analysis. TH levels in the SCG and extracerebral blood vessels were determined by Western blotting and immunocytochemistry, respectively. Circulating levels of 17beta-estradiol and prolactin (PRL) were quantified by RIA. Estrogen replacement significantly decreased NGF protein in the SCG and its targets, the external carotid artery, heart and extracerebral blood vessels. TH protein associated with the extracerebral blood vessels was also significantly decreased, but ERalpha levels were significantly increased in the heart following estrogen replacement. These results indicate that estrogen reduces NGF protein content in sympathetic vascular targets, which may lead to decreased sympathetic innervations to these targets, and therefore reduced sympathetic regulation. In addition, the estrogen-induced increase in ERalpha levels in the heart, a target tissue of the SCG, suggests that estrogen may sensitize the heart to further estrogen modulation, and possibly increase vasodilation of the coronary vasculature.
 ...
PMID:Estrogen regulation of neurotrophin expression in sympathetic neurons and vascular targets. 1728 2

Embryonic stem cells (ESC) can differentiate to derivatives of the three embryonic germ layers. Dopamine neurons have been produced from mouse and human ESC. This in vitro induction mimics the developmental program followed by dopaminergic cells in vivo. Production of dopamine neurons might have clinical applications for Parkinson's disease, which has a higher incidence in men than in women, suggesting a protective role for sex hormones, particularly progesterone and estradiol. These hormones exert many of their effects through the interaction with their nuclear receptors. In this study, we used a described 5-stage protocol for dopamine neuron differentiation of ESC, allowing neuronal commitment as evidenced by specific markers and by behavioural recovery of hemiparkinsonian rats after grafting. We studied the expression of steroid hormone receptors by immunoblot during this procedure and found an increase in the content of both A and B isoforms of progesterone receptor (PR) and a decrease in estrogen receptor alpha (ER-alpha) when cells were at the neural/neuronal stages, when compared with the amount found in initial pluripotent conditions. We also found the same pattern of PR and ER-alpha expression by immunocytochemistry. Ninety-two percent of dopamine neurons expressed progesterone receptors and only 19% of these neurons co-expressed tyrosine hydroxylase and ER-alpha. These results show a differential expression pattern of ER-alpha and PR isoforms during neuronal differentiation of ESC.
 ...
PMID:Changes in the content of estrogen alpha and progesterone receptors during differentiation of mouse embryonic stem cells to dopamine neurons. 1749 39

Copulatory behaviors in most rodents are highly sexually dimorphic, even when circulating hormones are equated between the sexes. Prairie voles (Microtus ochrogaster) are monomorphic in their display of some social behaviors, including partner preferences and parenting, but differences between the sexes in their masculine and feminine copulatory behavior potentials have not been studied in detail. Furthermore, the role of neonatal aromatization of testosterone to estradiol on the development of prairie vole sexual behavior potentials or their brain is unknown. To address these issues, prairie vole pups were injected daily for the first week after birth with 0.5 mg of the aromatase inhibitor 1,4,6-androstatriene-3,17-dione (ATD) or oil. Masculine and feminine copulatory behaviors in response to testosterone or estradiol were later examined in both sexes. Males and females showed high mounting and thrusting in response to testosterone, but only males reliably showed ejaculatory behavior. Conversely, males never showed feminine copulatory behaviors in response to estradiol. Sex differences in these behaviors were not affected by neonatal ATD, but ATD-treated females received fewer mounts and thrusts than controls, possibly indicating reduced attractiveness to males. In other groups of subjects, neonatal ATD demasculinized males' tyrosine hydroxylase expression in the anteroventral periventricular preoptic area, and estrogen receptor alpha expression in the medial preoptic area. Thus, although sexual behavior in both sexes of prairie voles is highly masculinized, aromatase during neonatal life is necessary only for females' femininity. Furthermore, copulatory behavior potentials and at least some aspects of brain development in male prairie voles are dissociable by their requirement for neonatal aromatase.
 ...
PMID:Sex differences and effects of neonatal aromatase inhibition on masculine and feminine copulatory potentials in prairie voles. 1837 36


1 2 Next >>