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Biomedical subjects

M K Vaughan

Publications and source records attributed to M K Vaughan.

At least 37 records · Page 2Linked to original sources

Harderian gland porphyrin, lysosomal and type II 5'-deiodinase rhythms in Sprague-Dawley and Fischer-344 rats kept under chronic long- or short-photoperiod conditions.

1. Harderian gland porphyrin concentrations were 1.5-fold higher in Fischer-344 male rats than in Sprague-Dawley male rats and there were no differences due to exposure to LD 14:10 (LP) or LD 10:14 (SP) lighting conditions for 8 weeks in either strain. 2. 24-hr periodic regression analyses of porphyrin concentration detected a significant rhythm in both lighting conditions in both strains, with no differences in acrophase due to lighting conditions. 3. In both strains, porphyrin levels were highest in the late phase-early dark period and fell during the early part of the dark period. 4. Acid phosphatase activity did not vary with time (circadian rhythm), strain or photoperiodic lighting condition. 5. Circadian rhythms in beta-glucuronidase, alpha-mannosidase and hexosaminidase activity were present in some instances, but, probably due to the low amplitude to these rhythms, a consistent effect of strain or housing condition was not found. When 24-hr rhythms were observed in either strain, the acrophase occurred during the afternoon-early evening daylight period. 6. A significant effect of strain on mean values of type II 5'-deiodinase activity was noted in Fischer-344 rats. 7. Significant rhythms in type II 5'-deiodinase activity were found in both strains exposed to LD 10:14.

Analysis of Variance↗

Low temperature stimulates pineal activity in Syrian hamsters.

The effect of 24-hr exposure to cold (5 degrees C) was studied in male Syrian hamsters adapted to short days (LD 8:16). Both pineal N-acetyltransferase (NAT) activity and pineal and serum concentrations of melatonin showed a clear, diel rhythm with a moderate but significant increase late in the dark period. The nighttime peak levels of NAT activity and pineal and serum melatonin were significantly higher in the animals that had been exposed to cold than in those remaining in warm (22 degrees C) conditions. The activity of type-II 5'-deiodinase (5'D) in the brown adipose tissue (BAT) was not different after 24 hr of cold exposure between cold- and warm-exposed hamsters, and the enzyme did not show any diel rhythmicity. It has been speculated that some effects of cold exposure may be simulated by melatonin treatment; the present data further support this notion. The apparent lack of response in BAT 5'D activity remains enigmatic and needs further investigation.

Adipose Tissue↗

Serum luteinizing hormone, prolactin, and thyrotropin and their pituitary subunit mRNA levels during proestrus in the Syrian hamster.

mRNA levels for alpha, luteinizing hormone beta (LH beta), and prolactin (Prl) were examined during the hamster estrous cycle, with sampling most frequent (1-hour intervals) on the afternoon of proestrus. These transcripts encode the peptide subunits for the pituitary hormones LH and Prl which are necessary for reproductive function. Serum hormone levels of LH and Prl, analyzed by 24-hour periodic regression, exhibited a 24-hour periodicity on proestrus characterized by a large surge peaking at about 18.00 h. Combining the data for non-proestrous days of the cycle disclosed a rhythm with similar timing for LH and Prl. Thyroid-stimulating hormone (TSH) and TSH beta RNA profiles during hamster proestrus are reported for the first time. Serum TSH exhibited a pronounced peak coincident with that of the other hormones on proestrus. Because of variations at other times on the day of proestrus, however, a 24-hour periodicity was not manifested by regressional analysis. Combined non-proestrous serum TSH data also revealed no consistently timed regressional 24-hour periodicity. During proestrus, pituitary mRNA values for alpha, LH beta, and Prl simultaneously exhibited a rise from the lowest to the highest of all proestrous values in the 3-5 h prior to the time of the pre-ovulatory peak of circulating hormone concentrations. RNA for TSH beta exhibited an earlier, broader peak on proestrus. Periodic regression indicated a significant 24-hour rhythm for alpha mRNA in data pooled from non-proestrous days (acrophase 05.00 h) and for TSH beta mRNA on proestrus (acrophase 04.54 h).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Endocrine and metabolic effects of life-long food restriction in rats.

The effects of chronic (40%) food restriction from 6 weeks of age were studied in 28-month-old male Fischer-344 rats; the results were compared with ad libitum-fed, old and young male rats at 28 and 3 months of age, respectively. Pituitary luteinizing hormone was similar in all old rats and was significantly lower than in young rats. In old ad libitum-fed, but not in food-restricted rats, serum levels of LH, testosterone and T4 were significantly lower than in young rats. Serum levels of T3 did not differ between young and old rats. Type-II 5'-deiodinase activity in brown adipose tissue was similar in both groups of old animals and was significantly depressed as compared with that in young rats. Serum levels of triglycerides were significantly depressed in food-restricted rats, but were significantly increased in ad libitum-fed rats as compared with young rats. Both groups of old rats had significantly elevated serum levels of cholesterol over that in young rats, but the level was significantly lower in food-restricted as compared to ad libitum-fed animals. The results are consistent with the notion that life-long food restriction tends to preserve the activity of many metabolic functions.

Aging↗

Melatonin and porphyrin in the harderian glands of the Syrian hamster: circadian patterns and response to autumnal conditions.

1. Adult male Syrian hamsters were killed at nine intervals during a 24 hr period in the autumn, after 2 months either indoors in controlled conditions or in natural outdoor conditions. 2. Harderian glands were taken for determination of N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT) activities and melatonin and porphyrin concentrations. 3. Mean 24 hr Harderian NAT and melatonin values were lower outside than inside. 4. Twenty-four hour melatonin rhythms were detected with similar daytime (afternoon) acrophases in both environmental conditions. 5. An NAT rhythm was seen only in animals kept inside, with a circadian maximum in the late dark phase. 6. Mean 24 hr HIOMT activity was slightly higher outdoors than indoors, and 24 hr rhythms were not detected in either condition. 7. Mean porphyrin concentrations were higher outdoors, with 24 hr rhythms detected in both conditions and a significantly earlier nocturnal circadian maximum outdoors.

Acetylserotonin O-Methyltransferase↗

Effects of acute cold exposure at night on pineal N-acetyltransferase activity and melatonin content in white-footed mice, Peromyscus leucopus.

1. Pineal N-acetyltransferase (NAT) activity in long-day white-footed mice (Peromyscus leucopus) exposed to cold soon after onset of darkness was depressed relative to controls, whereas mice exposed to cold later at night had slightly elevated enzyme activity. 2. NAT activity in short-day mice exposed to cold soon after lights off did not differ from controls. Pineal melatonin in these mice, however, did not rise, as it did in controls. 3. These results suggest that acute cold exposure may modulate NAT activity, which is controlled primarily by the L:D cycle.

Acetyltransferases↗

Pineal lysosomal enzyme circadian rhythms in male hamsters exposed to natural decreasing photoperiod and temperature conditions.

Circadian rhythms in acid phosphatase (ACP), hexosaminidase (HEX) and beta-glucuronidase (RON) activity were studied in the pineal glands of adult male Syrian hamsters exposed to control (20 +/- 2 degrees C and 14:10 LD) conditions or to naturally decreasing autumn photoperiod and temperature conditions (outside) for 8 weeks. Testes and testosterone levels (p less than 0.001 in both instances) were severely depressed in animals exposed to natural environmental conditions illustrating that the treatment period was of sufficient length to produce pineal-mediated gonadal atrophy. Significant rhythms were found in all enzymes in the pineal glands of control and outside animals with the exception of HEX activity in the control animals. Significant acrophase differences in outside vs. control animals were noted in ACP (7.9 hr earlier, p less than 0.001) and RON (9.8 hr later, p less than 0.001). A significant drop in RON and HEX activity (p less than 0.01 in both instances) was noted in association with the acute lights exposure in the morning to which control animals were exposed. The around-the-clock mean value of each enzyme was significantly lower in outside vs. control hamsters. These results demonstrate that environmental changes which provoke the pineal-mediated depression in gonadal activity also alter the activity of and shift the circadian rhythmicity of lysosomal enzymes in the pineal itself.

Acid Phosphatase↗

Inhibition of 5'-deiodination of thyroxine suppresses the cold-induced increase in brown adipose tissue messenger ribonucleic acid for mitochondrial uncoupling protein without influencing lipoprotein lipase activity.

Young adult male and female Djungarian hamsters were exposed to ambient temperatures of 23 or 0 C for 12 h; half of the animals in each group were treated with iopanoic acid to suppress the peripheral conversion of T4 to the thermotropically active thyroid hormone T3 by the enzyme 5'-deiodinase (5'D). Brown adipose tissue (BAT) mRNA for uncoupling protein (UCP), BAT lipoprotein lipase (LPL) activity, and 5'D activity were measured at the conclusion of the study. A temperature of 0 C produced large rises in 5'D and LPL activities and a similar large increase in UCP mRNA within the 12-h exposure period. When 5'D activity was inhibited with iopanoic acid, mRNA for UCP was reduced, while LPL activity was unaffected. The results show that the optimal production of mRNA for BAT UCP depends on the availability of T3; however, T3 is not required for the cold-induced activation of LPL activity in BAT.

Adipose Tissue, Brown↗

N-acetyltransferase activity in the Harderian glands of the Syrian hamster, Mesocricetus auratus, is regulated by androgens and by hormones of the pituitary-thyroid axis.

This study tested the hypothesis that activity of the enzyme N-acetyltransferase (NAT) in the Harderian gland of the Syrian hamster is regulated both by androgens and by hormones of the pituitary-thyroid axis. To test the effects of castration and hypothyroidism, intact or castrated male hamsters were given either tap water or methimazole in their drinking water for 3 weeks. Methimazole suppresses iodination of thyroglobulin, thereby decreasing circulating levels of thyroid hormones and increasing TSH levels. Hypothyroidism or castration caused elevated or depressed Harderian gland NAT activities respectively, compared with euthyroid controls. When castration and hypothyroidism were combined, the animals exhibited high NAT activity compared with castrated euthyroid males. To test the effects of castration and hyperthyroidism, male hamsters were given daily injections of thyroxine (T4) or diluent and were either castrated or left intact for 4 weeks. Intact animals given T4 had depressed Harderian NAT activity; serum thyroid hormone levels were elevated and TSH levels were depressed compared with those of intact controls. Castrated animals had depressed NAT activity below that of intact controls; serum thyroid hormone levels were normal but TSH levels were depressed. Castrated animals given T4 injections had NAT activity similar to that of euthyroid castrated hamsters; thyroid hormone levels were elevated but TSH levels were similar to those seen in euthyroid castrated hamsters. In another experiment, both T4 and tri-iodothyronine (T3) were equally effective in decreasing NAT activity in intact males. To determine the effects of the removal of pituitary influences, male hamsters were hypophysectomized. NAT activity in the Harderian glands of these animals was reduced compared with intact controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgens↗

Pineal lysosomal enzymes in the Syrian hamster: circadian rhythm and effects of castration or short photoperiod treatment.

A circadian rhythm in acid phosphatase and hexosaminidase was found in adult male hamsters exposed to a long photoperiod (14:10 h light/dark [LD]; lights on 06.00 h) and killed at 08.00, 14.00, 20.00, 02.00, 04.00, 05.50 and 0.615 h. Hexosaminidase and beta-glucuronidase activity at 02.00, 04.00 and 05.50 h (values pooled for these times before lights on) were significantly elevated compared to enzyme activity at 06.15 and 08.00 h (pooled values after lights on), suggesting a fall in activity associated with lights on. Hypogonadism was induced in female Syrian hamsters by exposure to a short photoperiod (10:14 h LD) until a majority of them were vaginally acyclic. Pineal lysosomal enzyme activities (acid phosphatase, beta-glucuronidase, hexosaminidase, alpha-arabinosidase and beta-galactosidase) were significantly elevated in short photoperiod-exposed animals compared to animals in 14:10 LD, when measured near the middle of the light phase. In the third experiment, castrated animals were used to determine if lowered androgen levels might also affect pineal lysosomal enzyme activity. The results indicated that light phase beta-glucuronidase, hexosaminidase and beta-glucosidase activities were lower in castrated males compared to their intact controls. In summary, these results demonstrate that (1) lysosomal enzyme activity is present in the Syrian hamster pineal, (2) changes can be observed which suggest involvement of this activity in pineal function and, (3) a circadian rhythm in enzyme activity is present with peak activity occurring during the night. In the short photoperiod and castration experiments, the changes in lysosomal enzyme activity could reflect either a hormonal manipulation or a change in circadian regulation of enzyme activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid Phosphatase↗

Bromocriptine prevents the castration-induced rise in porphyrin concentration in the harderian glands of the male Syrian hamster, Mesocricetus auratus.

The Harderian glands in Syrian hamsters exhibit a striking sexual dimorphism. Male Harderian glands show two cell types and low levels of porphyrins and melatonin. Of the enzymes involved in the synthesis of melatonin, N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT) show high and low activity levels, respectively. Female Harderian glands show but one cell type and have high porphyrin and melatonin levels, low NAT activity, and high HIOMT activity. In castrated males, the Harderian glands exhibit a female pattern of morphology, porphyrin levels, and indoleamine metabolism. In an attempt to determine whether prolactin in involved in this sexually dimorphic response of the Harderian glands, intact and castrated male and intact female hamsters were injected daily with 500 micrograms of bromocriptine, a dopamine agonist. Bromocriptine led to reduced serum prolactin levels in all groups. It had no apparent effect on the Harderian glands of intact males. In contrast, in castrated males bromocriptine prevented the postcastrational rise in porphyrin levels but had no effect on NAT or HIOMT activities. In females, bromocriptine treatment had no effect on porphyrin concentrations or HIOMT activity; it led to a statistically significant increase in NAT activity. We propose that testosterone inhibits Harderian porphyrin synthesis while dopamine or prolactin stimulates it.

Animals↗

Pineal sensitivity to nighttime swimming stress changes during the active season in Richardson's ground squirrels (Spermophilus richardsonii).

Melatonin synthesis in the pineal gland, which is primarily regulated by the environmental lighting regime, can also be influenced by other factors that elicit modifications in sympathetic tone. The objectives of this study were to determine if forced swimming alters the normal pattern of melatonin production in the pineal gland of the Richardson's ground squirrel (Spermophilus richardsonii). In early June, the squirrels were forced to swim for 10 min during the photophase or during the scotophase. In mid-July squirrels swam only during the scotophase. Animals were sacrificed 15, 30, or 60 min after the onset of swimming. Activities of pineal N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT) were assessed by radioenzyme assay, and pineal melatonin content was measured by radioimmunoassay. Daytime swimming elicited no major changes in enzyme activity or pineal melatonin. In June, swimming at night prevented the normal rises in NAT activity and pineal melatonin seen in nonswimming controls. In contrast, the pineals of squirrels that were tested 6 weeks later in mid-July did not appear to be as sensitive to nighttime swimming, as there were only minor differences in both NAT activity and melatonin content compared to controls. These results demonstrate that forced nighttime swimming, unlike several other aversive stimuli, can evoke changes in the normal pattern of pineal melatonin production in this species. Furthermore, the pineal's response to such stimuli may not be stable over the course of the active season.

Acetylserotonin O-Methyltransferase↗

Interaction of harderian glands, illumination, and temperature on thyroid hormones in golden hamsters.

In this study, Harderianectomy (Hdx) has been shown to differentially modify circulating levels of the thyroid hormones, T4 and T3, in male and female golden hamsters exposed to low photic intensities or to moderately low temperatures. Specifically, low photic intensities depress circulating levels of T4 in both control and Harderianectomized (Hdx) male and female hamsters. In addition, T3 is decreased in both control and Hdx males but not in females, as a consequence of reduced levels of illumination. Moderately low temperatures (10 degrees C) depress T4 in both control and Hdx males but not in females, while T3 is increased in both control male and female hamsters, and in Hdx males, but not Hdx females. The data suggest that the Harderian gland of males enhances the sensitivity of the TSH-thyroid axis to photic intensity and to lower temperatures, and further, that there is a considerable sexual difference in the role the Harderian glands may play in response to these two environmental factors.

Animals↗

Undernutrition potentiates melatonin effects in maturing female rats.

Prepubertal (21-22 days) female Sprague-Dawley rats were caged singly in either long (LP; 14:10 LD) or short (SP; 8:16 LD) photoperiod and fed ad libitum or underfed (1/2 the food intake of controls). Additionally, a fed and underfed group in LP received a daily sc injection of saline or 100 micrograms melatonin at 1700 h. Food restriction delayed vaginal opening and resulted in a reduction in body weight and in the weights of the pituitary, ovary and uterus in all underfed groups. Melatonin treatment (but not SP exposure) significantly enhanced the reduction in pituitary, ovarian and uterine weight compared to the underfed saline-treated controls. Thyroid weights were significantly increased in underfed LP and SP groups compared to their respective controls where melatonin treatment in either fed or underfed animals was ineffective. Underfeeding caused a significant rise in pituitary LH (except for SP-underfed group) and FSH concentrations and a fall in pituitary prolactin concentrations and plasma T3 levels. Melatonin injections in underfed rats significantly increased pituitary LH and FSH and decreased prolactin concentrations compared to underfed saline-treated animals. Plasma prolactin levels increased after melatonin administration in both fed and underfed rats. These observations emphasize that environmental influences such as undernutrition can alter the physiological status of immature animals and enhance the sensitivity of the neuroendocrine axis to the pineal and one of its hormones, melatonin.

Animals↗

Effects of inhibition of thyroid function and of cold on melatonin synthesis and porphyrin content in the Harderian glands of male Syrian hamsters, Mesocricetus auratus.

1. Indole metabolism and porphyrin content of the Harderian glands of the male Syrian hamster were measured as functions of drug-induced hypothyroidism and exposure to cold conditions. 2. Harderian gland N-acetyltransferase (NAT) activity was reduced from control levels by hypothyroidism induced by methimazole; exposure to cold had no effect on NAT activity. 3. Immunoreactive melatonin in the Harderian glands was unaffected by the state of thyroid secretion. However, immunoreactive melatonin content declined after 180 and 270 min, at 4 degrees C, suggesting that Harderian gland melatonin may be involved in thermoregulation. 4. Porphyrin content of the Harderian glands was not affected by either thyroid secretion or cold.

Animals↗

Activation of cerebrocortical type II 5'-deiodinase activity in Syrian hamsters kept under short photoperiod and reduced ambient temperature.

Cerebrocortical type II thyroxine 5'-deiodinase (5'-D II) was studied in the Syrian hamster. Animals maintained in 14 hr light/day and 20 degrees C ambient temperature and then subjected to acute cold exposure (4 degrees C) for 4 hours did not exhibit changes in cortical 5'-D II activity. Prolonged exposure of hamsters to natural autumnal short photoperiods and reduced ambient temperatures for 8 weeks increased cortical 5'-D II activity compared to hamsters maintained inside under controlled long photoperiod (14:10 LD) and temperature (20 +/- 2 degrees C) conditions. Animal given subcutaneous implants of melatonin and exposed to the natural autumnal condition for 8 weeks exhibited a greater increase in the cortical 5'-D II activity than that in hamsters with blank pellets kept under the same conditions of reduced photoperiod and temperature. Type II 5'-deiodinase activity was not affected by treatment with 6-methoxy-2-benzoxazolinone (6-MBOA), a compound with a chemical structure related to melatonin. All animals maintained outdoors in the natural photoperiod and temperature conditions had depressed circulating thyroxine (T4) and elevated triiodothyronine (T3) concentrations; neither implants of melatonin nor 6-MBOA affected these thyroid hormone levels. It is concluded that serum T4 is depressed and cerebrocortical 5'-D II activity is stimulated despite the elevation of T3 levels in this autumnal condition. These responses, unlike classic pineal-mediated responses to environmental changes, are not blocked by subcutaneous implants of melatonin. However, chronic administration of melatonin might augment the cortical 5'-D II response to low serum T4 or some other component of the autumnal condition.

Animals↗

Melatonin effects on prolactin secretion in pituitary-grafted male rats.

Melatonin influences prolactin (PRL) secretion through unknown mechanisms. This work was undertaken to study the effects of melatonin administration on PRL secretion in pituitary-grafted male rats. Melatonin administration 5 hours before dark resulted in a marked decrease of previously high basal plasma PRL levels in pituitary-grafted rats, whereas a marked increase was detected in sham-operated animals. Vehicle treatment did not modify basal PRL values in grafted or sham-operated animals. Luteinizing hormone-releasing hormone (LHRH) administration resulted in a marked decrease of plasma PRL levels in vehicle-treated, sham-operated or grafted rats, as well as in melatonin-treated sham-operated rats. An increase in PRL levels was shown in grafted rats treated with melatonin. Estradiol benzoate (EB) administration resulted in an increase in plasma PRL levels both in sham-operated and grafted vehicle-treated rats. No PRL response could be detected in sham-operated, melatonin-treated animals after EB administration. In pituitary-grafted animals given melatonin, PRL response to EB administration was slight and delayed. From these data, melatonin appears to modify PRL secretion through multiple complex mechanisms that may depend on the physiological status (hormonal and neurotransmitter) of the animals. A direct effect at the pituitary level altering lactotroph sensitivity seems to be one plausible explanation for the current findings, although an hypothalamic site of action cannot be excluded.

Animals↗