Kevin Rudeen - Academia.edu (original) (raw)
Papers by Kevin Rudeen
American Journal of Health Education, 2007
Alcohol Clin Exp Res, 1995
Ethanol exposure during critical periods of development results in alterations of central nervous... more Ethanol exposure during critical periods of development results in alterations of central nervous system morphology and function. In this study, the effects of acute ethanol exposure on the number of neurons expressing luteinizing hormone-releasing hormone (LHRH) messenger RNA (rnRNA) has been analyzed. Also, the expression of LHRH mRNA in the diagonal band of Broca/preoptic area (DBB/POA) was determined. Pregnant C57BU6J mice were intubated with two doses of a 25% solution of ethanol or water (2.9 g/kg body weight) 4 hr apart on gestation day 7 (G7), G10, or G l l . Animals were killed on 018, and in situ hybridization was utilized to detect neurons expressing LHRH mRNA. The number of neurons expressing LHRH mRNA was determined along their migration r0ute from the rostrum into the forebrain. Ethanol exposure on G7 did not significantly change the number of neurons expressing LHRH mRNA on 018 compared with that in control animals. However, the number of neurons expressing LHRH mRNA in the nasal septum area in animals exposed to ethanol on 010 or G11 was significantly less than the number in control animals ( p < 0.05). Prenatal ethanol exposure on any of the aforementioned treatment days did not alter the expression of LHRH mRNA at the level of the DBWPOA on 618 in ethanol-treated animals compared with control animals. Also, neuron-specific enolase mRNA expression at the level of the DBB/POA was not altered by prenatal ethanol exposure. Therefore, ethanol exposure on the aforementioned treatment days did not dflerentially affect LHRH mRNA expression compared with neuron-specific enolase mRNA expression at the level of the DBB/POA. These data suggest that acute ethanol exposure may have specific effects on a subset of the LHRH neuron population, depending on the day of ethanol exposure during gestation and the neuroanatomical region in which the LHRH neurons are located.
Molecular Mechanisms of Alcohol, 1989
Alcohol and Alcoholism
The neural membrane-bound enzymes, acetylcholinesterase, Na/K-ATPase and Ca-ATPase were examined ... more The neural membrane-bound enzymes, acetylcholinesterase, Na/K-ATPase and Ca-ATPase were examined in six brain areas in perinatal rats at 5, 15 and 25 days of age following alcohol exposure in utero. Female Wistar rats were mated with adult male Wistar rats and maintained on either a liquid diet containing ethanol (5% w/v) or on a control liquid diet for various periods during gestation and the perinatal period. These periods were: before and during gestation only (until birth of the offspring); before and during gestation and following birth; during only a period of gestation and continuing postnatally. Enzyme activity was determined by spectrophotometric methods in the following areas of the brain in each offspring: telencephalon, cerebellum, hippocampus, septal area, preoptic area, and medial basal hypothalamic area. Analysis of the data indicates that alcohol exposure in utero will heterogeneously decrease enzyme activity among the six brain areas when compared to enzyme activity in the same brain areas in animals which were not exposed to alcohol in utero. The activity of the three enzymes were most significantly reduced on day 5 of age, compared to levels in the control animals. Enzyme activity in each brain area was generally most significantly affected in animals exposed to alcohol both pre- and postnatally. The results indicate that fetal alcohol exposure reduces neuronal enzyme activity relative to the period of ethanol exposure in utero; the longer the period of time that alcohol was consumed by the mothers pre- and postnatally, the greater the effect of alcohol on the enzyme activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Biology of Reproduction
F1 hybrid New Zealand Black (NZB) x New Zealand White (NZW) (NZB/W) mice are hormone-sensitive mo... more F1 hybrid New Zealand Black (NZB) x New Zealand White (NZW) (NZB/W) mice are hormone-sensitive models of the human disease systemic lupus erythematosus. In this study, NZB/W fetuses produced by pregnant NZB mice were compared with F1 C57BL/6 x DBA/2 (C57/DBA2) hybrid fetuses produced by nonautoimmune C57BL/6 females. Dams of both strains were treated with testosterone or the androgen blocker flutamide to alter the hormonal environment in late gestation. Hormonal changes in male fetuses carried by treated dams were of interest because hormonal manipulation using either testosterone or flutamide has been shown to increase longevity in male NZB/W offspring. Testosterone-implanted NZB dams developed the expected elevations in circulating maternal testosterone, whereas C57BL/6 dams treated with either testosterone or flutamide had elevated maternal serum testosterone concentrations. The treatment-induced changes in circulating testosterone in NZB dams and C57BL/6 dams were not reflected ...
Journal of steroid biochemistry, 1990
The local formation of the testosterone metabolites 5 alpha-dihydrotestosterone and 17 beta-estra... more The local formation of the testosterone metabolites 5 alpha-dihydrotestosterone and 17 beta-estradiol within the hypothalamic-preoptic area (HPOA) is essential for the normal sexual differentiation of the male central nervous system (CNS) during a perinatal critical period in the rat. Testosterone, the substrate for these reactions, is derived primarily from synthesis within the fetal testis. Fetal alcohol exposure (FAE) during this critical period profoundly affects fetal testicular steroidogenesis as well as the sexual differentiation of the CNS. The present study was conducted to determine whether FAE directly affects the local metabolism of androgens within the developing CNS or whether reduced androgen substrate, via a testicular lesion, is a more likely explanation for the known effects of FAE on the CNS. The enzymatic activities of 5 alpha-reductase and aromatase were simultaneously quantitated in the newborn rat HPOA following FAE. Neither the enzymatic activity of 5 alpha-r...
Pharmacology Biochemistry and Behavior, 1981
Male golden hamsters preferentially consume alcohol solution when given a free-choice between wat... more Male golden hamsters preferentially consume alcohol solution when given a free-choice between water and the alcohol solution. The pineal gland has been implicated as influencing the predilection for the ethanol solution. Melatonin, a pineal hormone, was administered either daily for 11 weeks as a subcutaneous injection (25 micrograms/animal) or weekly as a subcutaneous beeswax implant (1 mg melatonin/24 mg beeswax) for 5 weeks to hamsters allowed a free-choice between water or a 10% ethanol solution. Food, water and alcohol consumptions were measured on a daily basis. Animals treated by daily injection with melatonin consumed slightly less ethanol than animals not given melatonin. In light-deprived animals given chronic implants of melatonin, alcohol consumption was reduced when compared to alcohol consumption by light-deprived hamsters not receiving melatonin. Melatonin treatment also resulted in reducing daily total fluid intake as well as ethanol consumption in light-deprived hamsters. The results indicate that the pineal gland may influence fluid consumption in the hamster, and indirectly alters the propensity of the hamster to consume alcohol.
Life Sciences, 1975
... IMMOBILIZATION STRESS ON SEROTONIN CONTENT AND TURNOVER IN REGIONS OF THE RAT BRAIN` William ... more ... IMMOBILIZATION STRESS ON SEROTONIN CONTENT AND TURNOVER IN REGIONS OF THE RAT BRAIN` William W. Morgen, P. Kevin Rudeen and Karla A. Pfeil Department of Anatomy, The University of Texas Health Science Center at San Antonio, San Antonio, T axas ...
Journal of Pineal Research, 1989
The effects of exogenous thyroid hormone administration on melatonin-induced gonadal atrophy were... more The effects of exogenous thyroid hormone administration on melatonin-induced gonadal atrophy were studied in young adult male hamsters. Animals were given daily afternoon injections of 25 micrograms melatonin and/or thrice-weekly injections of 7 micrograms thyroxine. A control group received injections of saline vehicle only. No significant effect of either treatment was seen on body weight. Melatonin-treated animals had significantly reduced testicular and seminal vesicle weights, compared with vehicle-treated control animals: serum T4 levels and the FT4I were reduced by melatonin treatment, but serum T3 and the FT3I were increased. No effect of melatonin was seen on in vitro T3 uptake. Thyroxine treatment alone, while leading to elevated serum T4 levels and FT4I, had no effect on T3, the FT3I, or T3 uptake. Thyroxine treatment normalized circulating T4 levels and the FT4I in melatonin-treated animals, without preventing the melatonin-induced testicular regression. The results are taken as evidence that the inhibitory effects of melatonin on gonadal and thyroid function are independently mediated.
Journal of Pineal Research, 1989
Female hamsters were treated each afternoon for 8 weeks with subcutaneous injections of 25 microg... more Female hamsters were treated each afternoon for 8 weeks with subcutaneous injections of 25 micrograms of either melatonin or vehicle solution. Animals were sacrificed in either the morning or afternoon of diestrus and proestrus, along with their respective melatonin-induced acyclic pairs. Melatonin-treated hamsters had significantly greater mean body weights than did the vehicle-treated hamsters (P less than 0.05). Terminal mean serum T4 levels and free thyroxine index (FT41) were significantly reduced (P less than 0.05) in melatonin-treated hamsters compared with values obtained from animals subjected to the vehicle alone. In addition, T4 levels, FT41, T3 levels, and FT31 were significantly influenced by day and time of sacrifice independently of the melatonin treatment. T3 uptake was significantly lower on the morning of proestrus in melatonin-treated animals. These results demonstrate that chronic afternoon melatonin administration in female hamsters results in the loss of estrous cyclicity, a significant gain in body weight, and the reduction of T4 levels and T3 uptake. Changes in serum T3 levels are a function of the time of sample collection and are not influenced by melatonin treatment. In addition, these data indicate that thyroid function in general changes during the estrous cycle in these animals.
Drug and Alcohol Dependence, 1986
Adult male rats exposed to alcohol in utero results in reduction of the volume of the sexually di... more Adult male rats exposed to alcohol in utero results in reduction of the volume of the sexually dimorphic nucleus of the preoptic area (SND-POA). Reduction of the volume of this nucleus is also significantly reduced in rats exposed to ethanol postnatally compared to the volume in animals not exposed to ethanol (P less than 0.05). The results indicate that ethanol exposure during the postnatal period of brain development in rats is equally effective as in utero ethanol exposure in development of the SDN-POA volume. This report substantiates others demonstrating the deleterious effects of ethanol consumption during the 'critical' period of brain development.
Developmental Brain Research, 1992
Prenatal ethanol exposure has been shown to result in craniofacial malformations as well as alter... more Prenatal ethanol exposure has been shown to result in craniofacial malformations as well as alterations of central nervous system morphology and function. Previous studies have demonstrated that acute ethanol exposure on gestational day 7 in the developing C57BL/6J mouse resulted in craniofacial abnormalities similar to that of children with fetal alcohol syndrome. We investigated the effect of ethanol on the migration and number of immunoreactive LHRH (irLHRH) neurons in this strain of mouse. Pregnant mice were intubated with 2 doses of a 25% solution of ethanol 4 h apart on gestational day 7 (G7). Control animals were intubated with water. Animals were sacrificed on G14 or G18 and immunocytochemistry was used to identify irLHRH neurons that were visualized by light microscopy. Fetal ethanol administration did not substantially affect the migration of the LHRH neurons from the medial nasal placode into the forebrain on G14 or G18. The total number of irLHRH neurons was not significantly different on G14 in ethanol-exposed animals as compared to the number in control animals. However, the total number of irLHRH neurons on G18 was significantly less (P less than 0.03) in 4 neuroanatomical regions in fetal ethanol-exposed mice compared to those in control mice; the nasal septum, the traverse area superior to the cribriform plate and ventromedial to the olfactory bulbs, the arch area which included the olfactory tubercle, medial septal nuclei and anterior hypothalamus in G18 fetuses, and preoptic area of the brain. Coronal investigation of the number of irLHRH neurons on G18 indicates that the loss of irLHRH neurons occurred predominantly in the medial region of the rostrum and brain.
Experientia, 1988
Adult pregnant rats were given either an ad libitum liquid diet containing 5% ethanol, a pair fed... more Adult pregnant rats were given either an ad libitum liquid diet containing 5% ethanol, a pair fed liquid diet or an ad libitum diet of rat chow and water administered throughout pregnancy and during the nursing period. The female offspring received either pregnant mare's serum gonadotrophin (PMSG) or PMSG followed by human chorionic gonadotrophin (hCG) at 30 days of age. The ovaries of fetal ethanol-exposed animals responded greater to the exogenous gonadotrophins with enhanced ovarian weights, increased numbers of ova shed, greater numbers of corpora lutea and antral follicles, and higher serum progesterone levels than in animals exposed to the control diets during gestation.
Molecular Brain Research, 1992
The effects of a single intraperitoneal injection of ethanol (3 g/kg b.wt.) on the hypothalamic-p... more The effects of a single intraperitoneal injection of ethanol (3 g/kg b.wt.) on the hypothalamic-pituitary-thyroid system was explored as a possible explanation of the hypothermic effect of ethanol. Serum thyroid hormones were significantly reduced by ethanol injection, but ethanol did not affect the cold-induced increase in serum thyroid hormones or thyroid-stimulating hormone (TSH). Since cold-exposure stimulates serum levels of TSH and thyroid hormones by stimulating thyroid-releasing hormone (TRH) release from neurons of the PVN, these findings demonstrate that ethanol did not block pituitary response to TRH or thyroid response to TSH. Paradoxically, ethanol increased cellular levels of TRH mRNA in the paraventricular nucleus (PVN), and blocked the cold-induced increase in TRH mRNA, suggesting that ethanol uncouples the regulation of TRH gene expression from the regulation of TRH release specifically in neurons of the PVN. Measurements of the effects of ethanol on TRH mRNA in thalamus, and beta-actin, vasopressin, somatostatin and corticotropin-releasing hormone (CRH) mRNAs in the PVN in addition to TRH mRNA revealed very specific effects of ethanol on the TRH neuronal system.
Alcoholism: Clinical and Experimental Research, 1988
Fetal ethanol exposure is known to produce CNS abnormalities. The molecular basis for these manif... more Fetal ethanol exposure is known to produce CNS abnormalities. The molecular basis for these manifestations observed in animals exposed to ethanol in utero may be explained by changes in regional catecholamine content and turnover. This study was designed to determine changes in catecholamine content and turnover in the cerebral cortex, cerebellum, medial basal hypothalamus, diencephalon, and septal area of male rats exposed to ethanol pre- and postnatally. Pregnant Sprague-Dawley rats were exposed to either an ad libitum liquid diet containing 35% ethanol-derived calories, an isocalorically matched liquid diet, or a diet consisting of laboratory chow and water. Regional alterations in catecholamine content and turnover in each of the brain areas were observed on postnatal Day 18. A regional variability was demonstrated in the effect of in utero ethanol exposure on catecholamine content and turnover. The most dramatic effect was found in the dopaminergic neurons of the medial basal hypothalamus where in utero ethanol exposed offspring had a significantly reduced DA content and turnover when compared to pups from both isocalorically matched and chow-fed dams. These data indicate that the dopaminergic neurons of this particular brain region are susceptible to alteration by ethanol exposure during development and that this alteration cannot be explained by changes in nutrition alone.
Alcoholism: Clinical and Experimental Research, 1989
We have examined the in utero effects of ethanol exposure on testicular steroidogenesis in newbor... more We have examined the in utero effects of ethanol exposure on testicular steroidogenesis in newborn male pups. Pregnant Sprague-Dawley rats were fed a liquid ethanol diet (35% ethanol-derived calories), a pair-fed isocaloric liquid diet, or a standard laboratory rat chow and water diet beginning on Day 12 of gestation and continuing through parturition. Although there were no significant differences in the enzymatic activity of 5-ene-3 beta-hydroxysteroid dehydrogenase/isomerase or C17,20-lyase, the enzymatic activity of 17 alpha-hydroxylase was significantly (p less than 0.01) reduced (i.e., approximately 36%) in the ethanol-exposed pups compared to those from the pair-fed and chow treatment groups. This lesion in testicular steroidogenic enzyme activity in newborn male pups exposed to alcohol in utero was transient as 17 alpha-hydroxylase activity from the ethanol-exposed animals returned to control levels by postnatal Day 20 and remained at control levels through adulthood (postnatal Day 60). These data suggest that the suppression of the perinatal testosterone surge in male rats exposed to alcohol in utero and the associated long term demasculinizing effects of prenatal ethanol exposure might be the result of reduced testicular steroidogenic enzyme activity in the perinatal animal.
Alcohol, 1990
We have previously reported detrimental effects of in utero ethanol exposure on testicular steroi... more We have previously reported detrimental effects of in utero ethanol exposure on testicular steroidogenic enzyme activity in newborn rats. It is now reported that in utero ethanol exposure during Day 12 of gestation through birth has no apparent morphological effect on the testes of Day 1 neonatal rats. It appears that the detrimental effects of ethanol on testicular steroidogenesis can be manifested at the biochemical level in the absence of morphological effects. However, it remained unknown as to whether acute exposure to ethanol would elicit similar biochemical effects as chronic ethanol exposure on testicular steroidogenesis. To test this possibility ethanol was injected at 0, 1, or 2 g/kg intraperitoneally (IP) into rats of various postnatal ages. Plasma ethanol and testosterone levels as well as testicular 17 alpha-hydroxylase and C17,20-lyase activities were measured. The results indicate that acute exposure to ethanol significantly (p less than 0.05) inhibits the catalytic activity of testicular 17 alpha-hydroxylase in the newborn rat testis. This inhibition was specific since the activity of testicular C17,20-lyase was not affected. In conjunction with the reduction in testicular enzyme activity, plasma testosterone levels were reduced to 30% of the control levels in newborn animals receiving ethanol. In older animals, i.e., postnatal Day 20 and 40 rats, plasma testosterone levels were reduced, but not significantly, following ethanol treatment. Furthermore, testicular enzyme activity was not significantly reduced following ethanol treatment in these same older animals. These results suggest that the newborn rat testis is especially sensitive to the effects of ethanol.
Alcohol, 1991
Fetal alcohol exposure (FAE) is associated with a variety of physiological and behavioral dysfunc... more Fetal alcohol exposure (FAE) is associated with a variety of physiological and behavioral dysfunctions, including deficits to reproductive function. FAE has also been shown to increase brain beta-endorphin levels. This study sought to determine whether the common delay of the onset of puberty in fetal alcohol-exposed animals could be due to increased opiate inhibition of LH release. Prepubertal female rats were injected with an opiate antagonist, naltrexone, over days 26-29. This naltrexone treatment led to an acceleration of vaginal opening and first estrus in FAE animals; had no effect on chow-fed or pair-fed controls. The vaginal opening and first estrus advancement in FAE animals occurred at a lower body weight indicating independence from growth-promoting effects of the drug treatment. It is concluded that delays in puberty in FAE animals are not directly due to pituitary pathology, but are related, at least in part, to increased inhibition of the LHRH neuron and functional impairment of gonadotrophin secretion.
Alcohol, 1990
JUNGKUNTZ-BURGETT, L., S. PAREDEZ AND P. K. RUDEEN. Reduced sensitivity ofhypothalamic-preoptic a... more JUNGKUNTZ-BURGETT, L., S. PAREDEZ AND P. K. RUDEEN. Reduced sensitivity ofhypothalamic-preoptic area norepinephrine and dopamine to testosterone feedback in adult fetal ethanol-exposed male rats. ALCOHOL 7(6) 513- 516, 1990.-Endocrine feedback of testosterone (T) in regulation of the hypothalamus is via the effects of T on the noradrenergic system. The current experiment was performed to determine the effects of fetal ethanol exposure (FEE) on the norepinephrine (NE) and dopamine (DA) content in the hypothalamic-preoptic area (HPOA) of adult male rats, and the response of NE and DA to T administration. Pregnant rats were exposed to diets containing either a liquid diet containing ethanol, a liquid diet containing sucrose isocalorically substituted for ethanol, or a chow and water diet. Male offspring were castrated or sham-operated at 45 days of age. The animals received either testosterone propionate (TP) or an oil vehicle. HPOA was collected at 55 days of age from each animal and NE and DA content was measured by HPLC-EC. There was no significant alteration of NE or DA content in the HPOA in FEE animals compared to catecholamine levels in animals derived from dams on the control diets. Castration had no significant effect on NE and DA content in the chow-fed or pair-fed animals. TP administration significantly reduced NE content only in the chow-and pair-fed animals but not in the FEE animals. DA content in the HPOA was not affected by castration, but TP administration also resulted in significantly reducing DA content in chow-and pair-fed castrate male rats but not in FEE castrate male rats. The results indicate that FEE alters the response of the noradrenergic and dopaminergic neurons in the HPOA to T administration. The inhibition of HPOA NE and DA content in castrated rats given high doses of TP is significantly diminished in fetal ethanol-exposed rats that is indicative of a reduction of neuronal responsiveness to steroid feedback regulation of the hypothalamus.
Journal of Interdisciplinary Cycle Research, 1977
Adult male albino rats were acclimated to shortened light/dark (L/D) photoperiods (L/D:1/4/23 3/4... more Adult male albino rats were acclimated to shortened light/dark (L/D) photoperiods (L/D:1/4/23 3/4 or L/D.2/22) concurrently with rats maintained in a L/D: 14/10 photoperiodic cycle. The activity and rhythmicity of pineal serotonin N‐acetyl‐transferase (NAT) was examined in the rats maintained in the shortened photoperiod at 4‐hr intervals for 24 hrs and compared to pineal NAT activity in rats maintained in
American Journal of Health Education, 2007
Alcohol Clin Exp Res, 1995
Ethanol exposure during critical periods of development results in alterations of central nervous... more Ethanol exposure during critical periods of development results in alterations of central nervous system morphology and function. In this study, the effects of acute ethanol exposure on the number of neurons expressing luteinizing hormone-releasing hormone (LHRH) messenger RNA (rnRNA) has been analyzed. Also, the expression of LHRH mRNA in the diagonal band of Broca/preoptic area (DBB/POA) was determined. Pregnant C57BU6J mice were intubated with two doses of a 25% solution of ethanol or water (2.9 g/kg body weight) 4 hr apart on gestation day 7 (G7), G10, or G l l . Animals were killed on 018, and in situ hybridization was utilized to detect neurons expressing LHRH mRNA. The number of neurons expressing LHRH mRNA was determined along their migration r0ute from the rostrum into the forebrain. Ethanol exposure on G7 did not significantly change the number of neurons expressing LHRH mRNA on 018 compared with that in control animals. However, the number of neurons expressing LHRH mRNA in the nasal septum area in animals exposed to ethanol on 010 or G11 was significantly less than the number in control animals ( p < 0.05). Prenatal ethanol exposure on any of the aforementioned treatment days did not alter the expression of LHRH mRNA at the level of the DBWPOA on 618 in ethanol-treated animals compared with control animals. Also, neuron-specific enolase mRNA expression at the level of the DBB/POA was not altered by prenatal ethanol exposure. Therefore, ethanol exposure on the aforementioned treatment days did not dflerentially affect LHRH mRNA expression compared with neuron-specific enolase mRNA expression at the level of the DBB/POA. These data suggest that acute ethanol exposure may have specific effects on a subset of the LHRH neuron population, depending on the day of ethanol exposure during gestation and the neuroanatomical region in which the LHRH neurons are located.
Molecular Mechanisms of Alcohol, 1989
Alcohol and Alcoholism
The neural membrane-bound enzymes, acetylcholinesterase, Na/K-ATPase and Ca-ATPase were examined ... more The neural membrane-bound enzymes, acetylcholinesterase, Na/K-ATPase and Ca-ATPase were examined in six brain areas in perinatal rats at 5, 15 and 25 days of age following alcohol exposure in utero. Female Wistar rats were mated with adult male Wistar rats and maintained on either a liquid diet containing ethanol (5% w/v) or on a control liquid diet for various periods during gestation and the perinatal period. These periods were: before and during gestation only (until birth of the offspring); before and during gestation and following birth; during only a period of gestation and continuing postnatally. Enzyme activity was determined by spectrophotometric methods in the following areas of the brain in each offspring: telencephalon, cerebellum, hippocampus, septal area, preoptic area, and medial basal hypothalamic area. Analysis of the data indicates that alcohol exposure in utero will heterogeneously decrease enzyme activity among the six brain areas when compared to enzyme activity in the same brain areas in animals which were not exposed to alcohol in utero. The activity of the three enzymes were most significantly reduced on day 5 of age, compared to levels in the control animals. Enzyme activity in each brain area was generally most significantly affected in animals exposed to alcohol both pre- and postnatally. The results indicate that fetal alcohol exposure reduces neuronal enzyme activity relative to the period of ethanol exposure in utero; the longer the period of time that alcohol was consumed by the mothers pre- and postnatally, the greater the effect of alcohol on the enzyme activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Biology of Reproduction
F1 hybrid New Zealand Black (NZB) x New Zealand White (NZW) (NZB/W) mice are hormone-sensitive mo... more F1 hybrid New Zealand Black (NZB) x New Zealand White (NZW) (NZB/W) mice are hormone-sensitive models of the human disease systemic lupus erythematosus. In this study, NZB/W fetuses produced by pregnant NZB mice were compared with F1 C57BL/6 x DBA/2 (C57/DBA2) hybrid fetuses produced by nonautoimmune C57BL/6 females. Dams of both strains were treated with testosterone or the androgen blocker flutamide to alter the hormonal environment in late gestation. Hormonal changes in male fetuses carried by treated dams were of interest because hormonal manipulation using either testosterone or flutamide has been shown to increase longevity in male NZB/W offspring. Testosterone-implanted NZB dams developed the expected elevations in circulating maternal testosterone, whereas C57BL/6 dams treated with either testosterone or flutamide had elevated maternal serum testosterone concentrations. The treatment-induced changes in circulating testosterone in NZB dams and C57BL/6 dams were not reflected ...
Journal of steroid biochemistry, 1990
The local formation of the testosterone metabolites 5 alpha-dihydrotestosterone and 17 beta-estra... more The local formation of the testosterone metabolites 5 alpha-dihydrotestosterone and 17 beta-estradiol within the hypothalamic-preoptic area (HPOA) is essential for the normal sexual differentiation of the male central nervous system (CNS) during a perinatal critical period in the rat. Testosterone, the substrate for these reactions, is derived primarily from synthesis within the fetal testis. Fetal alcohol exposure (FAE) during this critical period profoundly affects fetal testicular steroidogenesis as well as the sexual differentiation of the CNS. The present study was conducted to determine whether FAE directly affects the local metabolism of androgens within the developing CNS or whether reduced androgen substrate, via a testicular lesion, is a more likely explanation for the known effects of FAE on the CNS. The enzymatic activities of 5 alpha-reductase and aromatase were simultaneously quantitated in the newborn rat HPOA following FAE. Neither the enzymatic activity of 5 alpha-r...
Pharmacology Biochemistry and Behavior, 1981
Male golden hamsters preferentially consume alcohol solution when given a free-choice between wat... more Male golden hamsters preferentially consume alcohol solution when given a free-choice between water and the alcohol solution. The pineal gland has been implicated as influencing the predilection for the ethanol solution. Melatonin, a pineal hormone, was administered either daily for 11 weeks as a subcutaneous injection (25 micrograms/animal) or weekly as a subcutaneous beeswax implant (1 mg melatonin/24 mg beeswax) for 5 weeks to hamsters allowed a free-choice between water or a 10% ethanol solution. Food, water and alcohol consumptions were measured on a daily basis. Animals treated by daily injection with melatonin consumed slightly less ethanol than animals not given melatonin. In light-deprived animals given chronic implants of melatonin, alcohol consumption was reduced when compared to alcohol consumption by light-deprived hamsters not receiving melatonin. Melatonin treatment also resulted in reducing daily total fluid intake as well as ethanol consumption in light-deprived hamsters. The results indicate that the pineal gland may influence fluid consumption in the hamster, and indirectly alters the propensity of the hamster to consume alcohol.
Life Sciences, 1975
... IMMOBILIZATION STRESS ON SEROTONIN CONTENT AND TURNOVER IN REGIONS OF THE RAT BRAIN` William ... more ... IMMOBILIZATION STRESS ON SEROTONIN CONTENT AND TURNOVER IN REGIONS OF THE RAT BRAIN` William W. Morgen, P. Kevin Rudeen and Karla A. Pfeil Department of Anatomy, The University of Texas Health Science Center at San Antonio, San Antonio, T axas ...
Journal of Pineal Research, 1989
The effects of exogenous thyroid hormone administration on melatonin-induced gonadal atrophy were... more The effects of exogenous thyroid hormone administration on melatonin-induced gonadal atrophy were studied in young adult male hamsters. Animals were given daily afternoon injections of 25 micrograms melatonin and/or thrice-weekly injections of 7 micrograms thyroxine. A control group received injections of saline vehicle only. No significant effect of either treatment was seen on body weight. Melatonin-treated animals had significantly reduced testicular and seminal vesicle weights, compared with vehicle-treated control animals: serum T4 levels and the FT4I were reduced by melatonin treatment, but serum T3 and the FT3I were increased. No effect of melatonin was seen on in vitro T3 uptake. Thyroxine treatment alone, while leading to elevated serum T4 levels and FT4I, had no effect on T3, the FT3I, or T3 uptake. Thyroxine treatment normalized circulating T4 levels and the FT4I in melatonin-treated animals, without preventing the melatonin-induced testicular regression. The results are taken as evidence that the inhibitory effects of melatonin on gonadal and thyroid function are independently mediated.
Journal of Pineal Research, 1989
Female hamsters were treated each afternoon for 8 weeks with subcutaneous injections of 25 microg... more Female hamsters were treated each afternoon for 8 weeks with subcutaneous injections of 25 micrograms of either melatonin or vehicle solution. Animals were sacrificed in either the morning or afternoon of diestrus and proestrus, along with their respective melatonin-induced acyclic pairs. Melatonin-treated hamsters had significantly greater mean body weights than did the vehicle-treated hamsters (P less than 0.05). Terminal mean serum T4 levels and free thyroxine index (FT41) were significantly reduced (P less than 0.05) in melatonin-treated hamsters compared with values obtained from animals subjected to the vehicle alone. In addition, T4 levels, FT41, T3 levels, and FT31 were significantly influenced by day and time of sacrifice independently of the melatonin treatment. T3 uptake was significantly lower on the morning of proestrus in melatonin-treated animals. These results demonstrate that chronic afternoon melatonin administration in female hamsters results in the loss of estrous cyclicity, a significant gain in body weight, and the reduction of T4 levels and T3 uptake. Changes in serum T3 levels are a function of the time of sample collection and are not influenced by melatonin treatment. In addition, these data indicate that thyroid function in general changes during the estrous cycle in these animals.
Drug and Alcohol Dependence, 1986
Adult male rats exposed to alcohol in utero results in reduction of the volume of the sexually di... more Adult male rats exposed to alcohol in utero results in reduction of the volume of the sexually dimorphic nucleus of the preoptic area (SND-POA). Reduction of the volume of this nucleus is also significantly reduced in rats exposed to ethanol postnatally compared to the volume in animals not exposed to ethanol (P less than 0.05). The results indicate that ethanol exposure during the postnatal period of brain development in rats is equally effective as in utero ethanol exposure in development of the SDN-POA volume. This report substantiates others demonstrating the deleterious effects of ethanol consumption during the 'critical' period of brain development.
Developmental Brain Research, 1992
Prenatal ethanol exposure has been shown to result in craniofacial malformations as well as alter... more Prenatal ethanol exposure has been shown to result in craniofacial malformations as well as alterations of central nervous system morphology and function. Previous studies have demonstrated that acute ethanol exposure on gestational day 7 in the developing C57BL/6J mouse resulted in craniofacial abnormalities similar to that of children with fetal alcohol syndrome. We investigated the effect of ethanol on the migration and number of immunoreactive LHRH (irLHRH) neurons in this strain of mouse. Pregnant mice were intubated with 2 doses of a 25% solution of ethanol 4 h apart on gestational day 7 (G7). Control animals were intubated with water. Animals were sacrificed on G14 or G18 and immunocytochemistry was used to identify irLHRH neurons that were visualized by light microscopy. Fetal ethanol administration did not substantially affect the migration of the LHRH neurons from the medial nasal placode into the forebrain on G14 or G18. The total number of irLHRH neurons was not significantly different on G14 in ethanol-exposed animals as compared to the number in control animals. However, the total number of irLHRH neurons on G18 was significantly less (P less than 0.03) in 4 neuroanatomical regions in fetal ethanol-exposed mice compared to those in control mice; the nasal septum, the traverse area superior to the cribriform plate and ventromedial to the olfactory bulbs, the arch area which included the olfactory tubercle, medial septal nuclei and anterior hypothalamus in G18 fetuses, and preoptic area of the brain. Coronal investigation of the number of irLHRH neurons on G18 indicates that the loss of irLHRH neurons occurred predominantly in the medial region of the rostrum and brain.
Experientia, 1988
Adult pregnant rats were given either an ad libitum liquid diet containing 5% ethanol, a pair fed... more Adult pregnant rats were given either an ad libitum liquid diet containing 5% ethanol, a pair fed liquid diet or an ad libitum diet of rat chow and water administered throughout pregnancy and during the nursing period. The female offspring received either pregnant mare's serum gonadotrophin (PMSG) or PMSG followed by human chorionic gonadotrophin (hCG) at 30 days of age. The ovaries of fetal ethanol-exposed animals responded greater to the exogenous gonadotrophins with enhanced ovarian weights, increased numbers of ova shed, greater numbers of corpora lutea and antral follicles, and higher serum progesterone levels than in animals exposed to the control diets during gestation.
Molecular Brain Research, 1992
The effects of a single intraperitoneal injection of ethanol (3 g/kg b.wt.) on the hypothalamic-p... more The effects of a single intraperitoneal injection of ethanol (3 g/kg b.wt.) on the hypothalamic-pituitary-thyroid system was explored as a possible explanation of the hypothermic effect of ethanol. Serum thyroid hormones were significantly reduced by ethanol injection, but ethanol did not affect the cold-induced increase in serum thyroid hormones or thyroid-stimulating hormone (TSH). Since cold-exposure stimulates serum levels of TSH and thyroid hormones by stimulating thyroid-releasing hormone (TRH) release from neurons of the PVN, these findings demonstrate that ethanol did not block pituitary response to TRH or thyroid response to TSH. Paradoxically, ethanol increased cellular levels of TRH mRNA in the paraventricular nucleus (PVN), and blocked the cold-induced increase in TRH mRNA, suggesting that ethanol uncouples the regulation of TRH gene expression from the regulation of TRH release specifically in neurons of the PVN. Measurements of the effects of ethanol on TRH mRNA in thalamus, and beta-actin, vasopressin, somatostatin and corticotropin-releasing hormone (CRH) mRNAs in the PVN in addition to TRH mRNA revealed very specific effects of ethanol on the TRH neuronal system.
Alcoholism: Clinical and Experimental Research, 1988
Fetal ethanol exposure is known to produce CNS abnormalities. The molecular basis for these manif... more Fetal ethanol exposure is known to produce CNS abnormalities. The molecular basis for these manifestations observed in animals exposed to ethanol in utero may be explained by changes in regional catecholamine content and turnover. This study was designed to determine changes in catecholamine content and turnover in the cerebral cortex, cerebellum, medial basal hypothalamus, diencephalon, and septal area of male rats exposed to ethanol pre- and postnatally. Pregnant Sprague-Dawley rats were exposed to either an ad libitum liquid diet containing 35% ethanol-derived calories, an isocalorically matched liquid diet, or a diet consisting of laboratory chow and water. Regional alterations in catecholamine content and turnover in each of the brain areas were observed on postnatal Day 18. A regional variability was demonstrated in the effect of in utero ethanol exposure on catecholamine content and turnover. The most dramatic effect was found in the dopaminergic neurons of the medial basal hypothalamus where in utero ethanol exposed offspring had a significantly reduced DA content and turnover when compared to pups from both isocalorically matched and chow-fed dams. These data indicate that the dopaminergic neurons of this particular brain region are susceptible to alteration by ethanol exposure during development and that this alteration cannot be explained by changes in nutrition alone.
Alcoholism: Clinical and Experimental Research, 1989
We have examined the in utero effects of ethanol exposure on testicular steroidogenesis in newbor... more We have examined the in utero effects of ethanol exposure on testicular steroidogenesis in newborn male pups. Pregnant Sprague-Dawley rats were fed a liquid ethanol diet (35% ethanol-derived calories), a pair-fed isocaloric liquid diet, or a standard laboratory rat chow and water diet beginning on Day 12 of gestation and continuing through parturition. Although there were no significant differences in the enzymatic activity of 5-ene-3 beta-hydroxysteroid dehydrogenase/isomerase or C17,20-lyase, the enzymatic activity of 17 alpha-hydroxylase was significantly (p less than 0.01) reduced (i.e., approximately 36%) in the ethanol-exposed pups compared to those from the pair-fed and chow treatment groups. This lesion in testicular steroidogenic enzyme activity in newborn male pups exposed to alcohol in utero was transient as 17 alpha-hydroxylase activity from the ethanol-exposed animals returned to control levels by postnatal Day 20 and remained at control levels through adulthood (postnatal Day 60). These data suggest that the suppression of the perinatal testosterone surge in male rats exposed to alcohol in utero and the associated long term demasculinizing effects of prenatal ethanol exposure might be the result of reduced testicular steroidogenic enzyme activity in the perinatal animal.
Alcohol, 1990
We have previously reported detrimental effects of in utero ethanol exposure on testicular steroi... more We have previously reported detrimental effects of in utero ethanol exposure on testicular steroidogenic enzyme activity in newborn rats. It is now reported that in utero ethanol exposure during Day 12 of gestation through birth has no apparent morphological effect on the testes of Day 1 neonatal rats. It appears that the detrimental effects of ethanol on testicular steroidogenesis can be manifested at the biochemical level in the absence of morphological effects. However, it remained unknown as to whether acute exposure to ethanol would elicit similar biochemical effects as chronic ethanol exposure on testicular steroidogenesis. To test this possibility ethanol was injected at 0, 1, or 2 g/kg intraperitoneally (IP) into rats of various postnatal ages. Plasma ethanol and testosterone levels as well as testicular 17 alpha-hydroxylase and C17,20-lyase activities were measured. The results indicate that acute exposure to ethanol significantly (p less than 0.05) inhibits the catalytic activity of testicular 17 alpha-hydroxylase in the newborn rat testis. This inhibition was specific since the activity of testicular C17,20-lyase was not affected. In conjunction with the reduction in testicular enzyme activity, plasma testosterone levels were reduced to 30% of the control levels in newborn animals receiving ethanol. In older animals, i.e., postnatal Day 20 and 40 rats, plasma testosterone levels were reduced, but not significantly, following ethanol treatment. Furthermore, testicular enzyme activity was not significantly reduced following ethanol treatment in these same older animals. These results suggest that the newborn rat testis is especially sensitive to the effects of ethanol.
Alcohol, 1991
Fetal alcohol exposure (FAE) is associated with a variety of physiological and behavioral dysfunc... more Fetal alcohol exposure (FAE) is associated with a variety of physiological and behavioral dysfunctions, including deficits to reproductive function. FAE has also been shown to increase brain beta-endorphin levels. This study sought to determine whether the common delay of the onset of puberty in fetal alcohol-exposed animals could be due to increased opiate inhibition of LH release. Prepubertal female rats were injected with an opiate antagonist, naltrexone, over days 26-29. This naltrexone treatment led to an acceleration of vaginal opening and first estrus in FAE animals; had no effect on chow-fed or pair-fed controls. The vaginal opening and first estrus advancement in FAE animals occurred at a lower body weight indicating independence from growth-promoting effects of the drug treatment. It is concluded that delays in puberty in FAE animals are not directly due to pituitary pathology, but are related, at least in part, to increased inhibition of the LHRH neuron and functional impairment of gonadotrophin secretion.
Alcohol, 1990
JUNGKUNTZ-BURGETT, L., S. PAREDEZ AND P. K. RUDEEN. Reduced sensitivity ofhypothalamic-preoptic a... more JUNGKUNTZ-BURGETT, L., S. PAREDEZ AND P. K. RUDEEN. Reduced sensitivity ofhypothalamic-preoptic area norepinephrine and dopamine to testosterone feedback in adult fetal ethanol-exposed male rats. ALCOHOL 7(6) 513- 516, 1990.-Endocrine feedback of testosterone (T) in regulation of the hypothalamus is via the effects of T on the noradrenergic system. The current experiment was performed to determine the effects of fetal ethanol exposure (FEE) on the norepinephrine (NE) and dopamine (DA) content in the hypothalamic-preoptic area (HPOA) of adult male rats, and the response of NE and DA to T administration. Pregnant rats were exposed to diets containing either a liquid diet containing ethanol, a liquid diet containing sucrose isocalorically substituted for ethanol, or a chow and water diet. Male offspring were castrated or sham-operated at 45 days of age. The animals received either testosterone propionate (TP) or an oil vehicle. HPOA was collected at 55 days of age from each animal and NE and DA content was measured by HPLC-EC. There was no significant alteration of NE or DA content in the HPOA in FEE animals compared to catecholamine levels in animals derived from dams on the control diets. Castration had no significant effect on NE and DA content in the chow-fed or pair-fed animals. TP administration significantly reduced NE content only in the chow-and pair-fed animals but not in the FEE animals. DA content in the HPOA was not affected by castration, but TP administration also resulted in significantly reducing DA content in chow-and pair-fed castrate male rats but not in FEE castrate male rats. The results indicate that FEE alters the response of the noradrenergic and dopaminergic neurons in the HPOA to T administration. The inhibition of HPOA NE and DA content in castrated rats given high doses of TP is significantly diminished in fetal ethanol-exposed rats that is indicative of a reduction of neuronal responsiveness to steroid feedback regulation of the hypothalamus.
Journal of Interdisciplinary Cycle Research, 1977
Adult male albino rats were acclimated to shortened light/dark (L/D) photoperiods (L/D:1/4/23 3/4... more Adult male albino rats were acclimated to shortened light/dark (L/D) photoperiods (L/D:1/4/23 3/4 or L/D.2/22) concurrently with rats maintained in a L/D: 14/10 photoperiodic cycle. The activity and rhythmicity of pineal serotonin N‐acetyl‐transferase (NAT) was examined in the rats maintained in the shortened photoperiod at 4‐hr intervals for 24 hrs and compared to pineal NAT activity in rats maintained in