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R L Cooper

Publications and source records attributed to R L Cooper.

194 records · Page 11Linked to original sources
PubMedDate not supplied

The dithiocarbamate fungicide thiram disrupts the hormonal control of ovulation in the female rat.

Thiram has been reported to inhibit dopamine-beta-hydroxylase (D beta H), thereby affecting norepinephrine (NE) synthesis. Because NE is a neurotransmitter that is known to play an important role in the hypothalamic regulation of pituitary function, the acute effects of the thiram on the hormonal control of ovulation in the rat were investigated. Ovariectomized, estrogen-primed female rats were given a single injection of thiram (0, 6, 12, 25, 50, and 100 mg/kg, i.p.) at 1100 h and serum LH was measured in serial bleeds. Thiram at 100 and 50 mg/kg completely blocked the LH surge in all rats tested, while 12 and 25 mg/kg blocked the surge in 40 and 75% of the treated animals, respectively. Six mg/kg had no effect. Ovulation was then assessed in intact, proestrous females in response to thiram administration (0, 12, 25, or 50 mg/kg) at 0900, 1100, 1300, or 1800 h. Ovulation was blocked by 25 and 50 mg/kg at 1300 h in all rats, but when injected at 1100 h only the 50 mg/kg dose was effective. No such blockade was found with 50 mg/kg injected at 0900 and 1800 h. To assess the influence of thiram on the LH surge in intact rats, additional females were dosed at 1300 h on the day of proestrus and blood collected over that same day. Thiram at 50 mg/kg blocked the LH surge in all rats, while 25 mg/kg blocked the surge in 60% of the females tested. No effect occurred with 12 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Effect of atrazine on ovarian function in the rat.

The effect of the chlorotriazine herbicide, atrazine, on ovarian function was studied in Long-Evans hooded (LE-hooded) and Sprague-Dawley (SD) rats. Atrazine was administered by gavage for 21 d to females displaying regular 4-d estrous cycles. In both strains, 75 mg/kg/d disrupted the 4-d ovarian cycle; however, no distinct alteration (i.e., irregular cycles but not persistent estrus or diestrus) was apparent at this dose. At 150 mg/kg/d, atrazine induced repetitive pseudopregnancies in females of both strains. The highest dose tested (300 mg/kg/d) also induced repetitive pseudopregnancies in the SD females, while the ovaries of the LE-hooded female appeared regressed and the smear cytology was indicative of the anestrous condition. Although a NOAEL was not established, the doses employed in this experiment were in excess of those used in chronic feeding studies in which an early onset of mammary gland tumors was noted. These data demonstrate that atrazine can disrupt ovarian function and bring about major changes in the endocrine profile of the female.

Animals↗
PubMedDate not supplied

Blockade of ovulation in the rat by the fungicide sodium N-methyldithiocarbamate: relationship between effects on the luteinizing hormone surge and alterations in hypothalamic catecholamines.

Sodium N-methyldithiocarbamate (SMD), also known as metam sodium, is a commonly employed soil fungicide and nematocide. Structurally related dithiocarbamates have been found to decrease norepinephrine (NE) synthesis by suppressing the activity of dopamine-beta-hydroxylase. Because brain hypothalamic catecholamine (CA) activity is involved in generating the proestrus afternoon surge in blood luteinizing hormone (LH) which stimulates the final stages of ovulation, this study explored the effect of SMD on this hormonal trigger and its relationship to changes in hypothalamic CAs. Ovariectomized, steroid-primed Long-Evans rats showed a dose-related (25-100 mg/kg, IP) suppression of the surge and a drop in NE when SMD was given at 1100 h, a few h prior to the expected LH rise. The surge effect was reversed by the alpha-adrenergic agonist clonidine. With cycling rats, a decline with dose (50-300 mg/kg, 1300 h, proestrus) was seen in the percentage of ovulating females, with earlier injections (0900 h) being less effective at the highest dose. At all doses, low circulating levels of LH and prolactin at 1600 h suggested either a blockade in the proestrus surges of each hormone or a displacement in their time of occurrence. Anterior and posterior hypothalamic NE fell by 3 h postinjection and was accompanied by a rise in dopamine, while serotonin was unchanged. Although there was a distinct parallel between the alterations in regional CAs and the incidence of ovulation at the high doses of SMD, the relationship did not hold as the dose decreased. A similar dissociation between ovulation and CAs was seen when equimolar doses of SMD or methylisothiocyanate, a principal metabolite, were given by gavage. At the regional level of analysis employed, the data indicate that while IP injections of SMD are able to block the LH surge and ovulation in these rats, the dose-response relationship suggests that, along with induced alterations in CA metabolism, an additional factor may be involved in the observed effects.

Animals↗
PubMedDate not supplied

Strain comparisons of atrazine-induced pregnancy loss in the rat.

Atrazine was administered by gavage, in 1% methylcellulose, to F344 Sprague-Dawley (SD), and Long Evans (LE) rats at 0, 25, 50, 100, or 200 mg/kg/day on gestation days 6 through 10. The dams were allowed to deliver and litters were examined postnatally. The F344 strain was the most sensitive to atrazine's effects on pregnancy, showing full-litter resorption (FLR) at >/=50 mg/kg. In surviving F344 litters, prenatal loss was increased at 200 mg/kg. In SD and LE rats, FLR occurred only at 200 mg/kg. Delayed parturition was seen at >/=100 mg/kg in F344 and SD rats. Regarding maternal toxicity, the SD dams were the most sensitive, with weight loss at >/=25 mg/kg. When 200 mg/kg was administered to F344 rats on days 11 through 15 (after the LH-dependent period of pregnancy), no FLR was seen. These findings suggest that atrazine-induced FLR is maternally mediated, and consistent with loss of LH support of the corpora lutea.

Animals↗
PubMedDate not supplied

Blockade of ovulation in the rat by systemic and ovarian intrabursal administration of the fungicide sodium dimethyldithiocarbamate.

Dithiocarbamates, acting as inhibitors of catecholamine synthesis, have been reported to block ovulation in female rats following systemic administration by suppressing the neural noradrenergic signaling involved in triggering the ovulatory surge of luteinizing hormone. The ovaries also synthesize norepinephrine and receive noradrenergic input via sympathetic innervation, and it has been suggested that such input may play a role in follicular maturation and ovulation. The current experiments investigated whether the dithiocarbamate fungicide dimethyldithiocarbamate (DMDTC) would block oocyte release in normally cycling rats when administered systemically during the proestrous presurge period, and if so, would the compound also have a comparable direct ovarian effect on ovulation in response to a local intrabursal exposure of one ovary late on the day of vaginal proestrus. The results showed that a dose-related suppression of oocyte release was present in response to both intraperitoneal and intrabursal (IB) injections. But these effects appear to be mediated through different mechanisms. The unilateral IB injections were effective only on the exposed side for each ovarian pair, while no alterations were seen in ovarian norepinephrine. IB administration 24 h earlier blocked ovulation on both sides, while hCG injections were able to restore ovulation on the noninjected side only, implying that diestrous DMDTC was inhibiting the LH surge. The data indicate that while an effect on hypothalamic catecholamine synthesis may underlie the ovulatory blockade following intraperitoneal DMDTC administration, it does not appear to be involved in the response to local ovarian exposure. Moreover, the blockade in response to the diestrous IB exposure likely involves two separate mechanisms, one attributable to an alteration in ovarian hormonal feedback to the brain (or pituitary), inhibiting the LH surge, and the other associated with a direct, as yet undetermined, effect on local preovulatory events within the ovary.

Animals↗
PubMedDate not supplied

Perinatal exposure to estrogenic compounds and the subsequent effects on the prostate of the adult rat: evaluation of inflammation in the ventral and lateral lobes.

Although the effects of estrogenic compounds administered during the perinatal period on the size and morphology of the prostate have been well documented, the effects of such exposures on inflammatory changes in the prostate have not been well characterized. Since neonatal estradiol exposure has been shown to cause periods of hyperprolactinemia later in life and a relationship exists between high prolactin levels and rat lateral prostate inflammation, we hypothesized that an exposure to environmental compounds with estrogenic activity could result in an increase in lateral prostate inflammation in adulthood. To investigate this possibility and compare differences between estrogen agonists and antagonists, we examined the effect of a perinatal exposure to 17beta-estradiol, the insecticide methoxychlor, the partial estrogen agonist tamoxifen, and the pure antiestrogen ICI 182,780. Dams were dosed from gestation day (GD)18 to parturition and then the pups were dosed from postnatal day (PND) 1 to 5 with 0.1 mL of a solution of 0.355 mM and .0178 mM by sc injection, respectively, of all compounds in sesame oil, except for methoxychlor, which was administered only to the dam by gavage from GD 18 through PND 5 at a dose of 50 mg/kg in sesame oil. At 90 d of age, the weight of the lateral and ventral prostate in the estradiol group was significantly decreased. Tamoxifen caused a decrease in the weight of the lateral prostate, whereas the ventral lobe was not affected. ICI 182,780 did not alter prostate weight. The methoxychlor exposure increased the lateral lobe weight, but the ventral lobe weight was not affected. In the estradiol and tamoxifen groups, an inflammatory infiltrate was observed in the ventral prostates in 45.0 and 27.8% of the animals, respectively. There was a significant increase in the percent and severity of inflammation in the lateral prostate (as determined by a myeloperoxidase or neutrophil quantification assay) in the estradiol, tamoxifen, and methoxychlor groups as compared to controls. The ICI group was comparable to the controls in both ventral and lateral lobes. This study demonstrates that perinatal exposure to estrogenic compounds can result in alterations in the size of the adult prostate and increase the incidence of prostatitis.

Aging↗
PubMedDate not supplied

Characterization of pregnancy outcome following thiram-induced ovulatory delay in the female rat.

A single injection of the dithiocarbamate fungicide, thiram, suppresses the proestrous surge of LH and delays ovulation for 24 h. In this study, we examined fertility after a thiram-induced delayed ovulation. Females were injected with thiram (50 mg/kg, IP) on proestrus (1300 h) and mated on the following evening. Control and thiram-treated, but nondelayed, females were injected and mated on the same day. The number of females in the thiram-delayed group that became pregnant was reduced and litter size on GD 20 was reduced: however, no obvious morphological anomalies were seen. The number of pregnant females and litter size was not altered in the thiram-nondelayed rats, indicating that it is the thiram-induced delay in ovulation and not the exposure to thiram per se that was responsible for altered pregnancy outcome. On GD 7 and 11, the number of live fetuses per litter was reduced in the delayed females, but the number of implantation sites was not different from controls. On GD 11 the mean developmental score, head length, crown-rump length, and somite number in the delayed group were also reduced, indicating retarded development of live embryos. These results demonstrate that delayed ovulation induced by a single thiram exposure does not alter the number of oocytes released or the number that implant. However, the concept from these females are compromised during midgestation.

Animals↗
PubMedDate not supplied

Regional patterning of hormones in the female rat anterior pituitary: disproportionate changes over the estrous cycle.

The present study addressed the possibility that regional differences exist in the typical patterning of anterior pituitary hormones seen over the estrous cycle. The results show that LH in the rostral area of the pituitary, significantly higher than in other regions on diestrus, rises markedly on proestrus before falling late on that afternoon to concentrations comparable to other areas. Smaller cyclic changes were seen for lateral and caudo-central areas. The pattern of regional FSH concentrations on diestrus, while similar to LH, does not show the proestrus fall in the rostral region. Prolactin declines from a high on diestrus I to a low on late proestrus, but no regional disparities are present. TSH shows distinct regional differences and a fall in concentrations that coincides with the reported rise in serum estradiol. These findings indicate that the preovulatory surge of LH may represent a regionally disproportionate event, possibly involving inequalities in the relative amounts of gonadotropin-releasing hormone reaching various areas of the pituitary or differences in the ability of this releasing hormone to trigger LH release.

Animals↗
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A randomised controlled trial of proprioceptive and balance training after surgical reconstruction of the anterior cruciate ligament.

A randomised controlled trial (29 participants) was used to compare a 6-week proprioceptive and balance exercise program with a 6-week strengthening program in the early phases of rehabilitation after anterior cruciate ligament (ACL) reconstruction. Measurements of functional activity were taken by a blinded assessor before the intervention and at the end of the 6 weeks. Results demonstrated that there were no significant differences between groups on hop testing at 6 weeks. For several items in the Cincinnati knee rating system and the patient specific functional scale however, the strengthening group improved more than the proprioceptive and balance group (p < .05). The hypothesis that proprioceptive and balance training would improve functional activity more than strengthening exercises was not supported. There was either no difference between the two forms of exercise or strength training may be more beneficial than proprioceptive and balance training in the early phase of rehabilitation after ACL reconstructive surgery.

Adult↗
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A systematic review of the effect of proprioceptive and balance exercises on people with an injured or reconstructed anterior cruciate ligament.

This systematic review investigated the effect of proprioceptive and balance exercise on outcomes following injury and surgical reconstruction of the anterior cruciate ligament (ACL). Five studies of high quality that offered empirical evidence by comparing one rehabilitation program to another were included in this review. There is some evidence that proprioceptive and balance exercise improves outcomes in individuals with ACL-deficient knees. Improvements in joint position sense, muscle strength, perceived knee joint function, and hop testing were reported following proprioceptive and balance exercise. Only one included study investigated proprioceptive exercise following ACL reconstruction. Benefits were noted in the proprioceptive group for measures of strength and proprioception; however, no benefits were noted for any measures of activity. No detrimental effects--such as increased passive joint laxity or decrease in strength--were noted when compared with standard rehabilitation programs for both ACL-deficient and ACL-reconstructed individuals. Further research is required to determine if proprioceptive and balance exercise improves long-term outcomes such as return to sport.

Anterior Cruciate Ligament↗
PubMedDate not supplied

Neuroendocrine and reproductive effects of contemporary-use pesticides.

Work in our laboratory has focused on the hypothesis that certain environmental contaminants will interfere with reproductive function because they disrupt the neuroendocrine regulation of gonadal function. In this article, we review the evidence that certain classes of contemporary-use pesticides alter gonadotropin secretion through a disruption of hypothalamic mechanisms. Specifically, we discuss the effect of formamidine and dithiocarbamate pesticides on the noradrenergic control of pituitary hormone secretion, ovarian function, and pregnancy in the rat. This is followed by a review of studies evaluating the effect of a chlorotriazine herbicide, atrazine, on the hormonal control of ovulation and lactation. We also discuss the physiological consequences of these endocrine alterations in the female, how toxicant-induced endocrine alterations may differ in physiological outcome in the male and female, and the fact that the reproductive risk assessment of some pesticides that act on the central nervous system (CNS) may be influenced by the development of tolerance.

Amidines↗
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The estrogenic and antiandrogenic pesticide methoxychlor alters the reproductive tract and behavior without affecting pituitary size or LH and prolactin secretion in male rats.

This study was designed to determine if long-term exposure to high doses of methoxychlor (M) would alter pituitary or testicular endocrine functions in either an estrogenic or antiandrogenic manner. Weanling male Long-Evans hooded rats were dosed daily with M (po) at 0, 200, 300, or 400 mg kg-1 day-1 for 10 months. Methoxychlor treatment delayed puberty by as much as 10 weeks and reduced fertility and copulatory plug formation in a dose-related manner at the initial mating. During mating, M-treated males exhibited shorter latencies to mount and ejaculate versus control males, but the number of intromissions prior to ejaculation was unaffected, indicating that M enhanced the arousal level in the males in an estrogen-dependent manner. Most treated males eventually mated but time-to-pregnancy was lengthened. Very low sperm counts were associated with infertility, while prolonged delays in puberty reduced fecundity. Methoxychlor treatment with 200 to 400 mg kg-1 day-1 failed to mimic the chronic effects of a sustained (8 months) low dose of estradiol-17 beta (3-mm silastic implants) on pituitary or testicular hormone levels. Estradiol administration increased pituitary weight 4-fold, serum levels of luteinizing hormone (LH) were reduced by almost 50%, and serum prolactin was increased 40-fold, while M did not affect any of these measures. These data demonstrate that M affects the CNS, epididymal sperm numbers, and the accessory sex glands and delays mating without significantly affecting the secretion of LH, prolactin, or testosterone. These data indicate that M did not alter pituitary endocrine function in either an estrogenic or antiandrogenic manner. To our knowledge, these data provide the first in vivo example of such a pronounced degree of target tissue selectivity to an environmental endocrine-disrupting chemical.

Animals↗
PubMedDate not supplied

Administration of potentially antiandrogenic pesticides (procymidone, linuron, iprodione, chlozolinate, p,p'-DDE, and ketoconazole) and toxic substances (dibutyl- and diethylhexyl phthalate, PCB 169, and ethane dimethane sulphonate) during sexual differentiation produces diverse profiles of reproductive malformations in the male rat.

Antiandrogenic chemicals alter sexual differentiation by a variety of mechanisms, and as a consequence, they induce different profiles of effects. For example, in utero treatment with the androgen receptor (AR) antagonist, flutamide, produces ventral prostate agenesis and testicular nondescent, while in contrast, finasteride, an inhibitor of 5 alpha-dihydrotestosterone (DHT) synthesis, rarely, if ever, induces such malformations. In this regard, it was recently proposed that dibutyl phthalate (DBP) alters reproductive development by a different mechanism of action than flutamide or vinclozolin (V), which are AR antagonists, because the male offsprings display an unusually high incidence of testicular and epididymal alterations--effects rarely seen after in utero flutamide or V treatment. In this study, we present original data describing the reproductive effects of 10 known or suspected anti-androgens, including a Leydig cell toxicant ethane dimethane sulphonate (EDS, 50 mg kg-1 day-1), linuron (L, 100 mg kg-1 day-1), p,p'-DDE (100 mg kg-1 day-1), ketoconazole (12-50 mg kg-1 day-1), procymidone (P, 100 mg kg-1 day-1), chlozolinate (100 mg kg-1 day-1), iprodione (100 mg kg-1 day-1), DBP (500 mg kg-1 day-1), diethylhexyl phthalate (DEHP, 750 mg kg-1 day-1), and polychlorinated biphenyl (PCB) congener no. 169 (single dose of 1.8 mg kg-1). Our analysis indicates that the chemicals discussed here can be clustered into three or four separate groups, based on the resulting profiles of reproductive effects. Vinclozolin, P, and DDE, known AR ligands, produce similar profiles of toxicity. However, p,p'-DDE is less potent in this regard. DBP and DEHP produce a profile distinct from the above AR ligands. Male offsprings display a higher incidence of epididymal and testicular lesions than generally seen with flutamide, P, or V even at high dosage levels. Linuron treatment induced a level of external effects consistent with its low affinity for AR [reduced anogenital distance (AGD), retained nipples, and a low incidence of hypospadias]. However, L treatment also induced an unanticipated degree of malformed epididymides and testis atrophy. In fact, the profile of effects induced by L was similar to that seen with DBP. These results suggest that L may display several mechanisms of endocrine toxicity, one of which involves AR binding. Chlozolinate and iprodione did not produce any signs of maternal or fetal endocrine toxicity at 100 mg kg-1 day-1. EDS produced severe maternal toxicity and a 45% reduction in size at birth, which resulted in the death of all neonates by 5 days of age. However, EDS only reduced AGD in male pups by 15%. Ketoconazole did not demasculinize or feminize males but rather displayed anti-hormonal activities, apparently by inhibiting ovarian hormone synthesis, which resulted in delayed delivery and whole litter loss. In summary, the above in vivo data suggest that the chemicals we studied alter male sexual differentiation via different mechanisms. The anti-androgens V, P, and p,p'-DDE produce flutamide-like profiles that are distinct from those seen with DBP, DEHP, and L. The effects of PCB 169 bear little resemblance to those of any known anti-androgen. Only in depth in vitro studies will reveal the degree to which one can rely upon in vivo studies, like those presented here, to predict the cellular and molecular mechanisms of developmental toxicity.

Aminoimidazole Carboxamide↗