Estrogen alters MPTP-induced neurotoxicity in female mice: effects on striatal dopamine concentrations and release.
*MPTP Poisoning; 3; 4-Dihydroxyphenylacetic Acid/metabolism; Animals; Corpus Striatum/*drug effects/*metabolism; Dopamine/*metabolism; Estradiol/*pharmacology; Female; Inbred C57BL; Inbred Strains; Levodopa/pharmacology; Mice; Osmolar Concentration; Ovariectomy
The effects of estrogen on MPTP-induced neurotoxicity of the nigrostriatal dopaminergic system were examined in C57Bl and CD-1 mice. Ovariectomized mice with and without estrogen were treated with MPTP or its vehicle. The effects of these treatments on striatal dopamine concentrations and L-DOPA-stimulated dopamine and L-3,4-dihydroxyphenylacetic acid (DOPAC) release in vitro were determined. Dopamine concentrations of C57Bl mice receiving estrogen before MPTP were significantly greater than those of non-estrogen-treated MPTP mice as well as estrogen-treated mice receiving the MPTP vehicle. Dopamine concentrations of the CD-1 mice did not differ with these treatments. L-DOPA-evoked dopamine release values of estrogen-treated C57Bl mice were significantly increased compared with non-estrogen-treated mice. No such differences were observed in the
Dluzen D E; McDermott J L; Liu B
Journal of neurochemistry
1996
1996-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1046/j.1471-4159.1996.66020658.x" target="_blank" rel="noreferrer noopener">10.1046/j.1471-4159.1996.66020658.x</a>
Estrogen decreases corpus striatal neurotoxicity in response to
Female; Animals; Rats; Corpus Striatum/*drug effects; Dopamine/metabolism; Neurotoxins/*toxicity; Estradiol/*pharmacology; Oxidopamine/*toxicity; Parkinson Disease/*physiopathology; Sprague-Dawley; Animal; Disease Models; 3; 4-Dihydroxyphenylacetic Acid/metabolism
Ovariectomized rats treated or not with an estradiol pellet were subjected to an unilateral intrastriatal infusion of 6-hydroxydopamine (6-OHDA). Various parameters of nigrostriatal dopaminergic function as derived from measurements of dopamine and dihydroxyphenylacetic acid (DOPAC) concentrations were determined from the 6-OHDA lesioned and non-lesioned sides of the corpus striatum in these animals. Dopamine concentrations within the 6-OHDA lesioned striatum of estrogen-treated rats were significantly greater than non-estrogen-treated rats. There were no differences in striatal dopamine concentrations between estrogen- versus non-estrogen-treated rats on their non-lesioned side. In contrast to that of dopamine, no differences in DOPAC concentrations between estrogen and non-estrogen-treated rats were obtained within the 6-OHDA-lesioned side. The DOPAC concentrations on the non-lesioned side of the striatum were significantly greater in the non-estrogen-treated rats. These results demonstrate that estrogen significantly diminishes the depletion of striatal dopamine resulting from the neurotoxin 6-OHDA. The data obtained from the DOPAC determinations imply that this capacity of estrogen may be exerted through actions upon uptake processes of striatal dopaminergic neurons. Such findings suggest that estrogen may function as an important modulatory factor capable of attenuating degeneration within the corpus striatum, and in this way serve as a neuroprotectant of the nigrostriatal dopaminergic system.
Dluzen D
Brain research
1997
1997-09
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
Estrogen differentially modulates nicotine-evoked dopamine release from the striatum of male and female rats.
Animals; Corpus Striatum/drug effects/*metabolism; Dopamine/*metabolism; Estradiol/*pharmacology; Female; In Vitro Techniques; Kinetics; Male; Nicotine/*pharmacology; Orchiectomy; Ovariectomy; Rats; Sex Characteristics; Sprague-Dawley
In the present experiment we examined the effects of an in vitro infusion of nicotine (10 microM) upon dopamine release from superfused striatum of castrated male and female rats treated or not treated with estrogen. Estrogen exerted bidirectional effects on nicotine-evoked dopamine release as a function of the sex of the animal. Nicotine-evoked dopamine release was increased in estrogen treated females and decreased in estrogen treated males. Peak nicotine-evoked dopamine output from estrogen treated females was significantly greater than that of estrogen treated males. These results may be related to the gender differences in response to nicotine and smoking behavior.
Dluzen D E; Anderson L I
Neuroscience letters
1997
1997-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/s0304-3940(97)00487-4" target="_blank" rel="noreferrer noopener">10.1016/s0304-3940(97)00487-4</a>
Inhibition of striatal dopamine transporter activity by 17beta-estradiol.
Female; Animals; Rats; Dopamine/metabolism; Neostriatum/*drug effects/metabolism; Dopamine Plasma Membrane Transport Proteins; *Membrane Glycoproteins; *Nerve Tissue Proteins; Estradiol/*pharmacology; *Membrane Transport Proteins; Carrier Proteins/*antagonists & inhibitors; Synaptosomes/*drug effects/metabolism; Sprague-Dawley
Striatal synaptosomes from ovariectomized rats were prepared to examine the effect of 17beta-estradiol on [3H]dopamine uptake. Estradiol inhibited [3H]dopamine uptake in a dose-dependent manner, with an IC50 of 7.2 microM. Use of identical concentrations of progesterone had no effect on [3H]dopamine uptake. The effects of estradiol were exerted by decreasing the affinity of the transporter for dopamine, as revealed by a dose-dependent increase in the Km. The Km values for 0 (control), 10, and 100 microM estradiol were 108+/-11 258+/-44 and 415+/-40 nM, respectively, with each of the three concentrations tested being significantly different among each other. No statistically significant differences were obtained for the Vmax, with values for the three increasing doses being 9.2+/-0.8, 8.3+/-0.5 and 7.3+/-0.8 pmol/min per mg protein. These results demonstrate that estradiol, but not progesterone, inhibits striatal dopamine uptake by decreasing the affinity of the transporter for dopamine. Such a mechanism may serve as one of the bases for the modulatory effects of estradiol upon the nigrostriatal dopaminergic system.
Disshon K A; Boja J W; Dluzen D E
European journal of pharmacology
1998
1998-03
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
Preferential increase in pituitary prolactin versus vasoactive intestinal peptide as a function of estradiol benzoate dose in the ovariectomized rat.
Animals; Brain/drug effects/*metabolism; Dose-Response Relationship; Drug; Estradiol/*pharmacology; Female; Inbred Strains; Organ Specificity; Ovariectomy; Pituitary Gland/drug effects/*metabolism; Prolactin/blood/*metabolism; Rats; Thyrotropin/blood/metabolism; Vasoactive Intestinal Peptide/*metabolism
Vasoactive intestinal peptide (VIP) is synthesized in various tissues, including the anterior pituitary gland, where it may stimulate the release of PRL. Because estrogen plays a central role in the regulation of PRL, it becomes important to determine the effects of this steroid on both pituitary VIP and PRL. To study this, pituitary VIP and PRL and plasma PRL were assayed in ovariectomized rats after treatment with estradiol benzoate (EB; 0.007, 0.07, 0.7, 7 or 70 microgram/rat). Pituitary and plasma TSH were also determined as well as VIP content in the medial basal hypothalamus, suprachiasmatic region, cerebral cortex, and jejunum. Oil-treated rats served as controls. Injection of 0.7 or 7 microgram EB resulted in a significant increase in pituitary PRL without changing plasma PRL levels or pituitary VIP content compared to values in the control group. Only treatment with 70 microgram EB produced a significant increase in both pituitary VIP and PRL as well as in plasma PRL compared to control values. EB treatment at any of the doses used had no significant effect on pituitary and plasma TSH or VIP content in any of the other tissues examined. These data show that pituitary PRL and VIP are differentially regulated in response to estrogen. The increases in pituitary VIP and basal plasma PRL after treatment with the highest dose of EB suggest that pituitary VIP may be involved in the development of estrogen-induced hyperprolactinemia. These data also show that the regulations of pituitary VIP and TSH are independent of each other in the estrogen-treated rat.
Carrillo A J; Doherty P C; Guan X B; Sturtevant J R; Walro D G
Endocrinology
1991
1991-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1210/endo-128-1-131" target="_blank" rel="noreferrer noopener">10.1210/endo-128-1-131</a>
Quantification of vasoactive intestinal peptide immunoreactivity in the anterior pituitary glands of intact male and female, ovariectomized, and estradiol benzoate-treated rats.
*Ovariectomy; Animals; Anterior/*chemistry/drug effects/metabolism; Diestrus; Estradiol/*pharmacology; Female; Immunohistochemistry; Inbred Strains; Male; Pituitary Gland; Prolactin/blood/metabolism; Rats; Vasoactive Intestinal Peptide/*analysis/metabolism
There are considerable data suggesting that vasoactive intestinal peptide (VIP) is involved in the regulation of PRL secretion; however, the role and cell of origin of anterior pituitary VIP remain to be determined. Immunocytochemical (ICC) studies have generally failed to detect VIP-immunoreactive (IR) cells in the pituitary of the untreated rat, although VIP-IR cells have been observed in the pituitaries of hypothyroid or estrogen-treated rats. This study was designed to examine the cellular distribution and tissue content of VIP in the anterior pituitary gland of rats under selected endocrine conditions known to alter the rates of PRL and VIP synthesis and secretion. To this end, anterior pituitary VIP and PRL content (ICC and RIA) and serum PRL levels were determined in ovariectomized (OVX) and OVX rats 3 days after treatment with 7 or 70 micrograms estradiol benzoate (EB). For comparison, pituitary VIP and PRL content (ICC and RIA) and serum PRL levels in untreated male and diestrous female rats were determined. Immunostaining for VIP was accomplished using a newly developed primary antiserum. Significant numbers of VIP-IR cells per 5-microns section were found in the anterior pituitary glands of all animals examined (275 +/- 33 in diestrous to 481 +/- 103 cells in male rats). VIP was not colocalized with PRL in any of the pituitaries regardless of steroid treatment or sex. Furthermore, the number of VIP-IR cells per pituitary gland was not significantly correlated with sex or EB treatment. Treatment with 70 micrograms, but not 7 micrograms, EB significantly increased the pituitary content of VIP and serum PRL levels compared to those after ovariectomy. However, both EB treatments resulted in a significant increase in pituitary PRL content compared to that in untreated OVX rats. Pituitaries from male rats had several-fold more VIP and less PRL content than pituitaries from diestrous rats. These data show that 1) in contrast to previous ICC studies, VIP-IR cells are readily detected in the anterior pituitary of intact male and female and OVX as well as EB-treated rats; 2) VIP is localized to cells other than lactotrophs, regardless of the steroid background; and 3) marked changes in anterior pituitary VIP content are not accompanied by changes in VIP-IR cell number.
Carrillo A J; Phelps C J
Endocrinology
1992
1992-08
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1210/endo.131.2.1639033" target="_blank" rel="noreferrer noopener">10.1210/endo.131.2.1639033</a>
Sex steroid induction of gallstones in the male Syrian hamster.
Male; Animals; Body Weight; Organ Size; Cricetinae; Drug Combinations; Estradiol/*pharmacology; Mesocricetus; Medroxyprogesterone/*pharmacology; Cholelithiasis/*etiology; Endoplasmic Reticulum/drug effects/ultrastructure; Gallbladder/*drug effects/ultrastructure; Golgi Apparatus/drug effects/ultrastructure; Animal; Disease Models
Light (LM), transmission (TEM) and scanning (SEM) electron microscopic techniques were used to characterize morphologic changes induced in the gallbladder of Syrian hamsters following a one-month estradiol (E) and estradiol + medroxyprogesterone (E+MP) treatment. The TEM results were correlated with the SEM findings. Compared to control (C), E-treated surface epithelial cells contain abundant RER, enlarged Golgi, multivesicular (foamy-heterophagosomes) bodies or lipofuscin inclusions. A 10-day E treatment showed large vesicles develop and, after longer E treatment, they could coalesce and create some of the large multivesicular bodies. Interestingly, E+MP epithelia are characterized by distinct bulging apices where a large number of apical granules accumulate, and contain an anionic mucous core. After a 4-week E+MP treatment, even though all the hamsters were fed a diet with trace cholesterol, significant increase in hamster liver weight, serum level of cholesterol and HDL were measured and, correspondingly, gallstones were found exclusively in E+MP-treated hamsters. Our results showed that not only does the Syrian hamster provide an appropriate model to study experimental lithogenesis without manipulating the diet. In addition, MP appears to induce morphologic changes associated with the formation of gallstones.
Gilloteaux J; Kosek E; Kelly T R
Journal of submicroscopic cytology and pathology
1993
1993-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
The effect of estrogen administration in vivo upon catecholamine release in vitro from superfused hypothalamic tissue of ovariectomized pre-pubertal and adult mice.
*Ovariectomy; Aging/*metabolism; Animals; Catecholamines/*metabolism; Dopamine/metabolism; Estradiol/*pharmacology; Female; Hypothalamus/*drug effects/metabolism; Mice; Norepinephrine/metabolism; Organ Size/drug effects; Potassium/pharmacology; Uterus/drug effects/growth & development
In the present report we examined the effects of estrogen upon catecholamine release from superfused medial basal hypothalamic tissue fragments of pre-pubertal ovariectomized CD-1 mice. Prepubertal mice treated with estradiol benzoate (EB–5 micrograms x 2 days, sc), showed significantly reduced amounts of dopamine but no changes in norepinephrine release in response to a depolarizing concentration of potassium (30 mmol/L) compared with their respective groups receiving the oil vehicle. Since EB treatment reduced potassium stimulated dopamine release in these pre-pubertal mice, in a second experiment we compared the effects of EB versus oil vehicle treatment upon potassium stimulated dopamine release from the hypothalamus of the ovariectomized adult female mouse. Similar to that observed in the pre-pubertal mouse, EB treatment significantly reduced the amount of potassium stimulated dopamine release. Interestingly, the absolute amounts of potassium stimulated dopamine release was substantially greater in adult compared with pre-pubertal mice. These results demonstrate that the hypothalamic dopaminergic system of both pre-pubertal and adult mice show relatively similar responses to estrogen treatment but differ in absolute amounts of dopamine released.
Dluzen D; Attaran M; Liu B
Journal of endocrinological investigation
1994
1994-12
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1007/BF03347791" target="_blank" rel="noreferrer noopener">10.1007/BF03347791</a>
Use of in vitro superfusion to assess the dynamics of striatal dopamine clearance: influence of estrogen.
Animals; Corpus Striatum/drug effects/*physiology; Dopamine/*metabolism/pharmacology; Estradiol/*pharmacology; Female; Kinetics; Nomifensine/*pharmacology; Ovariectomy; Rats; Sprague-Dawley
To determine the feasibility of assessing dopamine uptake using in vitro superfusion, striatal tissue from ovariectomized female rats was infused with dopamine (1 microM), nomifensine (1 mM), or a combination of dopamine and nomifensine. Treatment with nomifensine or dopamine/nomifensine increased the recovery of dopamine in the effluent samples as compared to treatment with dopamine alone. In Experiment 2, the striatal tissue was treated with varying concentrations (0, 3, 30 or 300 nM) estradiol throughout the superfusion and subsequently given a dopamine (1 microM) challenge. The recovery of dopamine was enhanced in the presence of 3 and 30 nM estradiol. These results show that (1) in vitro superfusion can be used to dynamically evaluate dopamine recovery, and (2) estradiol, like nomifensine, increases the recovery of exogenously applied dopamine from the striata of ovariectomized female rats. Such increases in dopamine recovery with estrogen and similarities to that obtained with nomifensine suggest that estrogen may be inhibiting dopamine uptake from these striatal tissue fragments. Moreover, the doses at which estrogen can exert these effects insinuates a physiological role for this process. Our data provide a clear functional demonstration for one of the mechanisms by which estradiol can modulate striatal dopamine neurons, that of an uptake inhibitor. Such a mechanism has important implications with regard to estradiol's capacity to function as a neuroprotectant of the nigrostriatal dopaminergic system through inhibition of uptake of neurotoxins which can produce neurodegeneration of striatal dopamine neurons.
Disshon K A; Dluzen D E
Brain research
1999
1999-09
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/s0006-8993(99)01863-6" target="_blank" rel="noreferrer noopener">10.1016/s0006-8993(99)01863-6</a>