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Biomedical subjects

M K Vaughan

Publications and source records attributed to M K Vaughan.

At least 73 records · Page 4Linked to original sources

Adrenalectomy prevents changes in rat pineal melatonin content and N-acetyltransferase activity induced by acute insulin stress.

The activity of N-acetyltransferase (NAT) and the content of melatonin (MEL) in the rat pineal have been shown to be sensitive to several types of stressors. This study was designed to assess the role of the adrenals in mediating the effect of one such stressor, insulin-induced hypoglycemia, on pineal synthetic activity. Intact and bilaterally adrenalectomized (ADX) adult male rats were kept under light:dark cycles of 14:10 (lights on 0600 h) and injected intraperitoneally with 10 IU insulin at 1300 h, and groups (n = 8) were killed 2, 3, or 4 h postinjection. Plasma catecholamines were assayed by means of high performance liquid chromatography and radioimmunoassay was used to assess pineal NAT activity and MEL content. All injected groups were rendered hypoglycemic by insulin administration. Compared to uninjected controls, plasma epinephrine in hypoglycemic intact rats rose after 2 h, whereas epinephrine did not change in hypoglycemic ADX animals. The increase in epinephrine in intact animals was correlated with a rise in NAT activity at 2 h. Moreover, pineal MEL content at 2, 3, and 4 h was significantly greater than control values. In contrast, no changes in pineal biosynthetic function were found in ADX rats. This differential response by intact and ADX rats suggests that an adrenal product (possibly epinephrine) is responsible for mediating the stimulatory effects of acute insulin-induced hypoglycemic stress on the rat pineal.

Acetyltransferases↗

Elevated ambient temperature retards the atrophic response of the neuroendocrine-reproductive axis of male Syrian hamsters to either daily afternoon melatonin injections or to short photoperiod exposure.

Adult male Syrian (golden) hamsters, maintained under either 22 +/- 2 or 32 +/- 2 degrees C, were treated with 8 or 11 weeks of exposure to either long photoperiod (14:10), short photoperiod (8:16), or to long photoperiod with a daily afternoon melatonin injection. By 8 weeks, the animals kept at 22 degrees C and treated with daily afternoon melatonin injection exhibited a dramatic reduction in testicular and accessory sex organ weight, but the animals kept at 32 degrees C and treated in the same way exhibited only slight decreases in testicular and accessory organ weights. Short photoperiod caused a slight decrease in testicular and accessory organ weights of hamster kept at 22 degrees C, while it had no significant effects on reproductive organ weights of the animals maintained under 32 degrees C. By 11 weeks, the daily afternoon melatonin injection elicited further reduction in testicular and accessory organ weights of the animals maintained under both 22 and 32 degrees C. However, the reduction in animals kept at 32 degrees C was not as great as that in animals kept at 22 degrees C. Although short photoperiod caused an obvious decline in reproductive organ weights of the animals at 22 degrees C, only a slight decrease was seen in hamsters at 32 degrees C. As with reproductive organ weights, testosterone levels were depressed more rapidly and completely in animals maintained at 22 degrees C. These results indicate that elevated ambient temperature changes the rate at which the gonads of hamsters regress in response to daily afternoon melatonin injections or short photoperiod.(ABSTRACT TRUNCATED AT 250 WORDS)

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Influence of diet on photoperiod-induced gonadal regression in female hamsters.

Introduction of a seed/nut mixture (Lyric) to the diet of female golden hamsters was found to stimulate growth as well as to effect a delay in the reproductive response to a short photoperiod. In a series of experiments we found that 1) growth rates of hamsters offered the Lyric diet alone or in conjunction with the standard rodent diet exceeded those of hamsters offered only the standard rodent diet. 2) Hamsters fed the standard rodent diet for eight weeks, followed by the Lyric diet for four weeks remained reproductively functional in a short photoperiod; however, 3) most hamsters that were fed the Lyric diet or the standard rodent diet continuously for 12 or 16 weeks experienced reproductive atrophy in short photoperiods; 4) The presence of a vitamin/mineral supplement in the Lyric diet did not affect the incidence of reproductive degeneration in hamsters fed this diet continuously for 12 weeks; however, 5) the vitamin/mineral supplement in this experiment did influence weight gain in hamsters exposed to short photoperiods. We conclude that the Lyric diet, offered as a novel food source after eight weeks on a standard rodent diet, acts to delay the onset of reproductive atrophy in hamsters exposed to short photoperiods. The mechanism for such an effect is not known at this time.

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Effects of afternoon injections of O-acetyl-5-methoxytryptophol, melatonin or 5-methoxytryptophol in female Syrian hamsters.

Female Syrian hamsters were maintained in a 14:10 light: dark photoperiod (lights on 6 a.m.) and injected each afternoon between 4 p.m. and 6 p.m. with diluent or with 25 micrograms melatonin, O-acetyl-5-methoxytryptophol (aML) or 5-methoxytryptophol (ML). After 7 or 12 weeks of treatment, only the melatonin-treated hamsters were acyclic. Gross inspection of their ovaries revealed that they were smooth, brown, and devoid of corpora lutea and large follicles. Progesterone levels of the acyclic animals were midway between the high levels observed during estrus and postestrus and the low levels observed on cycle days 2 and 3. Additionally, the melatonin-treated hamsters had significantly reduced uterine weights and pituitary and plasma levels of prolactin. Hamsters treated with aML had significantly lower pituitary prolactin and plasma and pituitary levels of LH only at the 7 week timepoint. ML-treated hamsters had lower pituitary prolactin levels also at 7 weeks. The endocrine changes wrought by injections of aML and ML, however, were insufficient to ultimately affect vaginal cyclicity. In conclusion, it would appear that at the dose used and the time administered melatonin is the more active of the indoles tested in the female hamster, at least in terms of alterations in reproductive physiology.

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Cysteamine effects on somatostatin, catecholamines, pineal NAT and melatonin in rats.

The thiol reagent cysteamine was administered to adult male rats with the aim of investigating its effect on different neural and pineal components. As expected, immunoreactive somatostatin decreased in the median eminence (ME) (p less than 0.05) and gastric antrum (p less than 0.05) after cysteamine; however, no significant change was observed in the pineal IRS content after drug treatment. A decrease in norepinephrine was observed in the ME (p less than 0.001), hypothalamus (p less than 0.001) and pineal gland (p less than 0.05), together with a rise in ME (p less than 0.005) and hypothalamic dopamine (p less than 0.005) content; these results are consistent with a dopamine-beta-hydroxylase inhibiting effect of cysteamine. No effect was observed on hypothalamic serotonin and 5-hydroxyindole-acetic acid content. Pineal N-acetyltransferase (NAT) activity was significantly higher (p less than 0.05) after cysteamine than after saline, but no statistically significant effect was observed on pineal melatonin content. The mechanism involved in the NAT rise is presumably not related to the known stimulatory effect of norepinephrine, which fell after cysteamine. It is suggested that cysteamine may act at an intracellular level, inhibiting NAT degradation, an effect demonstrated in vitro and thought to be related to a thiol:disulfide exchange mechanism.

Acetyltransferases↗

Effect of light irradiance and wavelength on the Syrian hamster reproductive system.

The purpose of this study was to examine how the physical characteristics of light influence the short photoperiod-induced atrophy of the reproductive system. In the first experiment, groups of Syrian hamsters were exposed to a 14-h light, 10-h dark (14:10) photoperiod, a 11:13 photoperiod or a 11:13 photoperiod extended by 3 h of light at an irradiance of 20, 2, 0.2, or 0.002 microW/cm2. Animals in the 11:13 photoperiod and the 11:13 photoperiod extended by 0.02 and 0.002 microW/cm2 underwent reproductive regression, as evidenced by decreased testicular and accessory sex organ weight and pituitary PRL levels. In the second study, groups of hamsters were exposed to a 14:10, 11:13, or 11:13 photoperiod extended by 3 h of red, yellow, green, blue, or near-UV light at 0.2 microW/cm2. Animals in the 11:13 and the 11:13 photoperiod extended by red or yellow light underwent reproductive atrophy. These results demonstrate that light irradiance and wavelength are important determinants of the photoperiodic regulation of the Syrian hamster reproductive system.

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Reproductive effects of 6-chloromelatonin implants and/or injections in male and female Syrian hamsters (Mesocricetus auratus).

Adult female hamsters were injected each afternoon for 9 weeks with 2.5, 15 or 25 micrograms of melatonin or 6-chloromelatonin (CM). Each drug resulted in a significant dose-related depression in uterine, ovarian and anterior pituitary gland weights. Additionally, plasma and pituitary concentrations of prolactin fell with increasing dose of either indole whereas pituitary levels of LH and FSH were positively correlated with dose. There was no difference in effectiveness between the two drugs. Adult male hamsters treated for 10 weeks with daily afternoon injections of melatonin and a blank beeswax pellet had depressed testicular and accessory organ weights and plasma and pituitary concentrations of prolactin. Implantation of a 1 mg melatonin or CM beeswax pellet in hamsters concurrently receiving daily afternoon injections of melatonin prevented the organ weight and hormonal changes, except for plasma prolactin. Adult male hamsters treated for 10 weeks with daily afternoon injections of CM and a blank beeswax pellet had depressed reproductive organ weights and pituitary and plasma concentrations of prolactin; this depression in hormonal values and organ weights was totally prevented if the CM-injected hamsters were also bearing a beeswax-melatonin pellet. In conclusion, 6-chloromelatonin is as effective as melatonin with regards to antigonadotrophic and counter-antigonadotrophic effects in male and female Syrian hamsters.

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Effects of long-term treatment with melatonin or melatonin plus ectopic pituitary transplants on testicular LH/hCG and prolactin receptors in juvenile Syrian hamsters (Mesocricetus auratus).

Juvenile hamsters were injected daily with melatonin and some were also given transplants of 2 pituitaries under the kidney capsule. Weights of the testes and the accessory reproductive glands were reduced after 8 and after 12 weeks of melatonin treatment, but remained unaltered in animals treated with ectopic pituitary transplants. Levels of testicular LH/hCG receptors were significantly reduced by daily melatonin injections for 8 and 12 weeks. The presence of pituitary transplants in melatonin-injected hamsters prevented these reductions, and increased LH/hCG receptors above control levels. These changes in testicular LH/hCG receptors were closely related to alterations in serum prolactin concentration induced by melatonin and pituitary transplants. After 8, but not after 12 weeks of treatment, testicular prolactin receptor levels were reduced by melatonin and maintained by the presence of pituitary transplants. We conclude that: juvenile male hamsters become sensitive to the effects of daily melatonin injections when they reach maturity; daily melatonin injections can reduce the levels of testicular LH/hCG and prolactin receptors; and the effects of melatonin on LH/hCG and prolactin receptors are probably due to suppression of endogenous prolactin release.

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Photoperiodic and light spectral conditions which inhibit circulating concentrations of thyroxine in the male hamster.

Adult male Syrian hamsters were exposed daily for 12 weeks to 11 h/day of cool white fluorescent light (350 +/- 50 microW/cm2) followed by an additional 3 h of near ultraviolet (339-317 nm), blue (435-500 nm), green (515-550 nm), yellow (558-636 nm) or red (653-668 nm) light at an irradiance of 0.2 microW/cm2 or to total darkness. Animals exposed to the wavelengths between 558-668 nm (yellow or red half peak bandwidths) or those receiving a total of 13 h of darkness/day had suppressed circulating levels of thyroxine (T4), a depressed free T4 index (FT4I) and a higher T3/T4 ratio compared to animals receiving a total of 14 h of white light (350 +/- 50 microW/cm2). These results suggest that specific wavelengths of light can affect the neuroendocrine-thyroid axis.

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Superior cervical ganglionectomy results in the loss of pineal concretions in the adult male gerbil (Meriones unguiculatus).

Twelve weeks after bilateral superior cervical ganglionectomy, the number of pineal concretions in adult male gerbils was drastically decreased irrespective of photoperiodic treatment. These findings present further evidence that pineal concretions may be related to the metabolic activity of the gland. It is suggested that the pineal concretions of the gerbil are associated, in a yet unknown way, to the metabolism of the gland and that an active pineal is essential to maintain the large number of concretions seen in the normal state.

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Hormonal changes in burned hamsters.

Burned male Syrian hamsters (burn size 23% of body surface) exhibited reduced total (T4) and free (FT4) serum concentrations, a defect in T4 binding to serum proteins manifested by the T4 dialyzable fraction but not the in vitro T3 charcoal uptake, and reduced serum testosterone concentration. These changes are similar to those noted previously in burned humans. Unlike such patients, burned hamsters did not exhibit reduced serum T3 nor elevated rT3 concentrations in a reproducible manner. Pinealectomy performed before burning in hamsters did not prevent the burn-induced depression in serum T4 and testosterone.

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Diurnal sensitivity of the neuroendocrine-reproductive axis to the antigonadotrophic influence of melatonin in male Syrian hamsters with experimentally altered cortisol rhythms.

Two different experimental models were used to test if a temporal relationship exists between the rhythm of adrenal steroid secretion and the vulnerability of the hamster reproductive system to short photoperiod exposure or to the daily afternoon injection of melatonin. In the first experiment adrenalectomized hamsters were implanted with a cortisol pellet to provide a sustained, rather than rhythmic, level of the hormone. The animals were either placed in short photoperiod or given a daily afternoon melatonin injection. In both cases the gonads underwent atrophy. In the second experiment adrenalectomized hamsters were given a cortisol injection either in the morning (approx. 8 hr before the subsequent afternoon injection of melatonin) or in the afternoon (approx. 1 hr before the subsequent melatonin injection). Measurements of testicular and accessory organ weights 7 weeks later indicated regression of the reproductive system in both the groups when compared with their appropriate controls. Depressed levels of plasma LH, PRL, testosterone and thyroxine (T4) in these animals confirmed the melatonin induced gonadal collapse. The results suggest that apparently there is no temporal correlation between the rhythm of secretion of the adrenal steroids and the responsiveness of the reproductive system to late afternoon injection of melatonin. Interestingly, all the adrenalectomized cortisol injected control animals (not receiving melatonin) had depressed plasma LH and PRL while the testicular weights and plasma testosterone titers remain unaffected.

Adrenalectomy↗

Acute effects of a single afternoon melatonin injection on LH, prolactin, and pineal melatonin titers in the Syrian hamster.

Young adult male Syrian hamsters maintained in an LD 14:10 photo-period (lights out at 8 p.m.) were given a single injection of 25 micrograms melatonin or ethanolic-saline at 4 p.m. Animals from each group were sacrificed at 5 p.m., 4 a.m., and 10 a.m. following the injections. Pituitary and plasma LH and prolactin as well as pineal melatonin levels were determined in all animals by RIA. Pineal melatonin levels were significantly (p greater than 0.025) reduced at 10 a.m. in the melatonin treated group. Melatonin administration also suppressed pituitary LH levels at 4 a.m. and plasma LH levels at 10 a.m. Plasma prolactin concentrations at 4 a.m. and pituitary prolactin levels at both 5 p.m. and 10 a.m. were significantly elevated in melatonin treated hamsters compared with those given ethanolic-saline. These results indicate that exogenous melatonin has immediate effects on several hormones important in the regulation of reproductive events in this species. This acute injection model may therefore aid in the elucidation of melatonin's mechanism of action in the Syrian hamster.

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