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Biomedical subjects

L J Petterborg

Publications and source records attributed to L J Petterborg.

At least 19 recordsLinked to original sources

Effect of testosterone replacement on the alteration of steroid metabolism in the hypothalamic-preoptic area of male hamsters treated with melatonin.

Adult male hamsters were maintained under 14 hours of light per day and randomly assigned to groups that received daily afternoon melatonin (25 micrograms) or vehicle injections. Animals from both groups were killed following 4, 8, and 12 weeks of treatment. By 12 weeks, the melatonin-treated hamsters had significant reductions in the weights of the testes and seminal vesicles, serum testosterone levels, and activities did not differ between groups. In a second experiment, hamsters were hypothalamic-preoptic area (HPOA) aromatase activities. Hypothalamic-preoptic area 5 alpha-reductase activities did not differ between groups. In a second experiment, hamsters were again treated with melatonin or vehicle for 12 weeks prior to being killed. After 10 weeks of treatment, groups of melatonin-treated animals received subcutaneous silastic capsules (5, 10, or 20 mm) filled with testosterone. Animals in two other groups were given blank implants or no implants at all. Two weeks later, at autopsy, reproductive organ weights, serum testosterone levels, and HPOA aromatase activities were significantly suppressed by melatonin administration. 5 alpha-Reductase activity in the HPOA was not affected. Hamsters that had been given the 10- and 20-mm testosterone implants exhibited normal seminal vesicle weights and HPOA aromatase activities. These results suggest that melatonin-induced reduction of HPOA aromatase activity is mediated by decreased circulating levels of testosterone.

Animals↗

Effect of melatonin replacement on serum hormone rhythms in a patient lacking endogenous melatonin.

A potentially confounding variable inherent in studies designed to examine the effect of melatonin administration in humans is the presence of an endogenous melatonin rhythm in the experimental subjects. The effects of exogenous melatonin administration on serum hormone rhythms was recently examined in a male patient who lacked detectable circulating levels of endogenous melatonin. The patient's pineal gland had been destroyed five years previously in the course of treatment for a pineal astrocytoma. On three separate occasions, over approximately a one-year period, the patient was given daily oral melatonin replacement (2 mg/day, 1 mg/day and 0.5 mg/day). These experiments were designed to assess the effects of exogenous melatonin on serum growth hormone, prolactin, cortisol and testosterone rhythms. Analysis of blood samples collected every 2-4 hours periods both before and during melatonin replacement revealed that the exogenous melatonin rhythm was associated with improvements in self-reported sleep and mood ratings. Melatonin administration produced robust nocturnal peaks in serum growth hormone and prolactin levels immediately following ingestion of the hormone, while serum cortisol and testosterone rhythms were not influenced. These results suggest that melatonin may modulate the coordination and enhancement of selected biological rhythms in man.

Adult↗

Effect of a 15 minute light pulse on nocturnal serum melatonin levels in human volunteers.

Monitoring the daily melatonin rhythm during the course of phototherapy for affective disorders may be beneficial in assessing the efficacy of such treatments. It is therefore of interest to study the effects of the timing, duration, and intensity of bright light pulses on melatonin levels in normal subjects. To examine the effects of a single exposure to a brief burst of bright light on serum melatonin, groups of healthy human volunteers of both sexes were treated with a 15 minute pulse of bright light (350 cd/m2) early in the evening during the winter months. Serial blood samples were collected from each person and the effect of the light pulse on serum melatonin and cortisol levels determined. Melatonin levels were significantly but only transiently suppressed by the light pulse, while cortisol levels were not affected. These results demonstrate that short duration bright light treatments can influence the melatonin rhythm generating system in humans.

Female↗

Effects of light and an alpha-2-adrenergic agonist on serotonin N-acetyltransferase activity in chick pineal gland.

Pineal serotonin N-acetyltransferase (NAT) is the enzyme that catalyzes the production of N-acetylserotonin from serotonin and is the rate limiting step in the biosynthesis of melatonin in the chick pineal gland. Chick pineal NAT activity is decreased by light and by noradrenergic agents that act at the alpha-2-adrenergic receptor. Light-induced inhibition of nocturnal NAT activity can be demonstrated by exposing 4-day-old chicks to light, or by exposing pineal gland explants cultured in vitro either to light or to UK 14,304 (an alpha-2-adrenergic agonist). The inhibition by either light or UK 14,304 is preceded by a transient, but consistent rise in NAT activity. The paradoxical, transient light-induced rise in enzyme activity is mimicked by UK 14,304 which suggests a similarity in mechanisms of light and adrenergic signal transduction associated with the regulation of NAT activity.

Adrenergic alpha-Agonists↗

Ontogeny of light-induced decrease of N-acetyltransferase activity in explanted chick pineal glands.

The ontogeny of chick pineal serotonin N-acetyltransferase (NAT) activity was investigated in explanted chick pineal glands at 4, 10 and 21 d of age. Nocturnal levels of the enzyme and the response of the enzyme to light exposure were determined in pineal glands maintained in short-term culture at each age. The results indicate that nocturnal NAT activity was increased in the glands from older birds. Nocturnal levels of NAT activity at the time of the initiation of the experiment were threefold greater in glands from 21-d-old birds as compared to that in glands from 4-day-old chicks. The response to light was similar in all three ages examined; light induced a significant decrease in NAT activity within 60 min in explanted glands from 4-d-old chicks and within 180 min in the glands from the 10- and 21-d-old chicks. A paradoxical transient increase in enzyme activity occurred immediately (within 5 min) following light exposure which was significant in the glands from the youngest chicks, and present, but more variable, in the older chicks. These data indicate that the nocturnal enzyme activity is greater in glands from older birds, but that light exposure of explanted glands initiates a transient rise followed by a decrease in NAT activity at all three ages.

Acetyltransferases↗

Effects of daily afternoon melatonin administration on body weight and thyroid hormones in female hamsters.

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.

Animals↗

Identification of alpha 2-adrenergic receptors in chicken pineal gland using [3H]rauwolscine.

The norepinephrine-induced inhibition of avian pineal N-acetyltransferase activity appears to be mediated by alpha 2-adrenergic receptors. In this study, alpha 2-adrenergic receptors in the chicken pineal gland were directly identified by radioligand binding. Membrane preparations of pineal glands from chickens from 1 to 6 weeks of age were examined using [3H]rauwolscine, a selective alpha 2-adrenergic receptor antagonist, to characterize the binding sites. The results indicate no ontological change in either the affinity (KD) or density of receptor binding sites (Bmax) during the time span examined. The binding was saturable and of high affinity with a mean KD of 0.27 +/- 0.01 nM and a mean Bmax of 242 +/- 12 fmol/mg protein. Further characterization of these binding sites indicated that the alpha 2-adrenergic receptor is of the alpha 2A subtype, since prazosin and ARC-239 bound with low affinities and oxymetazoline bound with high affinity.

Adrenergic alpha-Antagonists↗

Exercise reduces gonadal atrophy caused by short photoperiod or blinding of hamsters.

The effect of voluntary exercise upon several reproductive parameters was assessed in male Syrian hamsters. Forty-two animals were caged in five groups and then blinded: Ten housed five per plastic cage; eight housed individually in plastic cages; six housed individually in plastic cages with 15 cm exercise wheels in the cage; eight housed in Wahmann steel activity cages with 36 cm wheels locked to prevent rotation; ten housed in functional Wahmann running wheel cages. At 16 weeks after blinding, animals with access to functional running wheels had significantly larger testes (3.7 +/- 1.0 g) than those with no wheels or locked wheels (1.86 +/- 0.6 g; mean +/- SD; p less than 0.001). These results suggested that voluntary exercise reduces testicular atrophy caused by blinding. A second experiment was run in which the animals were subjected to a short photoperiod (LD 6:18) for 12 weeks instead of blinding. Similar results were obtained except that access to the small exercise wheels did not affect testicular atrophy: Mean testicular mass of animals in individual cages = 0.79 +/- 0.3 g, small wheels = 0.74 +/- 0.4 g, functional Wahmann wheels, 2.56 +/- 1.0 g, locked Wahmann wheels 0.52 +/- 0.1 g (p less than 0.01).

Animals↗

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.

Animals↗

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.

Animals↗

Modification of testicular and thyroid function by chronic exposure to short photoperiod: a comparison in four rodent species.

Exposure of male Syrian hamsters (Mesocricetus auratus) for 10 weeks to short photoperiod (SP) providing 10 hr light: 14 hr darkness (10:14 LD) produced a significant reduction in the weights of the reproductive organs, plasma thyroxine (T4) levels and free T4 index (FT4I) compared to the values of animals exposed to long photoperiod (LP, 14:10 LD). C57bl male house mice (Mus musculus) kept in SP (10:14 LD) had reproductive organ weights equivalent to those of mice kept in long days (14:10 LD) and lower T3 uptake (T3U) values. Male gerbils (Meriones unguiculatus) exposed to 13 weeks of SP (10:14 LD) had lower body weights, testes and seminal vesicle weights and higher T3U values compared to LP (14:10 LD) controls. However, no effect was seen on plasma T4 and triiodothyronine (T3) values nor the FT4I and free T3 index (FT3I). White-footed male mice (Peromyscus leucopus) exposed to SP (8:16 LD) had significantly lower testes and seminal vesicle weights while plasma T4 and T3 levels were unaffected. Snell strain house mice (Mus musculus) exposed to SP (8:16 LD) had normal reproductive organ weights compared to the values of LP-exposed (16:8 LD) control animals. However, there was a significant depression in T3 and in the FT3I in the SP animals.

Animals↗

An immunocytochemical study of the luteinizing hormone-releasing hormone (LHRH) system in the white-footed mouse: effect of blinding and melatonin.

Previous studies have provided evidence that pineal-mediated gonadal atrophy involves the luteinizing hormone-releasing hormone (LHRH) system in some rodents. The purpose of the present study was to visualize the LHRH system in the brain of the white-footed mouse by immunocytochemical methods and to assess the influence of blinding or melatonin on the LHRH immunostaining characteristics of the median eminence. Six intact adult female mice and six adult males (two intact, two blinded, and two with subcutaneous melatonin-beeswax implants) treated for 6 wk were sacrificed by perfusion of fixative, and their brains were removed, cut into 60-micron sections and stained for LHRH by the peroxidase-antiperoxidase (PAP) method. Since the tissues were batch-processed in separate wells in a common chamber, semiquantitive comparisons may be made between similar sections from animals subjected to different treatments. The testes were also collected and prepared for microscopic examination. The distribution of LHRH-stained cell bodies and fibers was found to be essentially the same as has been described in other rodents, i.e., predominantly confined to the preoptic area and hypothalamus. The perikarya appear as unipolar and bipolar fusiform cells with "beaded fiber" type processes. In sections that included the median eminence of the blinded and melatonin-treated males, the degree of immunopositive staining appears to be greater than in the median eminence of untreated mice. The histological appearance of the testes from the treated animals revealed a profound inhibition of gametogenesis. These observations support the suggestion that pineal-mediated gonadal atrophy is the result of an inhibition of LHRH release from the median eminence.

Animals↗

Effects of injections and/or chronic implants of melatonin and 5-methoxytryptamine on plasma thyroid hormones in male and female Syrian hamsters.

Plasma thyroid hormone concentrations in male and female Syrian hamsters were evaluated in five experiments after two pineal indoles, melatonin (MEL) and 5-methoxytryptamine (5-MT), were administered as chronic s.c. implants and/or daily afternoon injections. Circulating concentrations of thyroxine (T4), ordinarily maintained by the long photoperiod (LD 14:10), were inhibited by daily afternoon injections of 25 micrograms MEL but not 5-MT in male (experiment 1) and female (experiment 2) Syrian hamsters. The suppressive effect of MEL injections on T4 concentration in the long photoperiod was prevented in both sexes by a s.c. beeswax pellet containing either 1 mg MEL or 5-MT. In the third experiment, various doses of MEL or 5-MT were injected each afternoon for 12 weeks to compare the effectiveness of these two indoles in reducing T4 concentrations in hamsters maintained in the long photoperiod. Only the highest dose (200 micrograms) of 5-MT effectively suppressed T4 concentrations whereas all doses of MEL (greater than or equal to 5 micrograms) significantly reduced plasma T4. MEL or 5-MT (1-1,000 micrograms) were implanted in beeswax pellets in male hamsters exposed to short photoperiod (LD 10:14) to determine if either indole could prevent the short photoperiod-induced suppression of T4 (experiments 4 and 5). Regression and covariance analyses showed a significant log dose-related elevation of T4 in these hamsters, indicating equal potency of MEL and 5-MT in preventing the short photoperiod-induced suppression of T4. 5-MT given by either injection or implantation raised plasma triiodothyronine (T3) in female (experiment 2) but not in male hamsters.(ABSTRACT TRUNCATED AT 250 WORDS)

5-Methoxytryptamine↗

Follicular growth and intraovarian and extraovarian oocyte release after daily injections of melatonin and 6-chloro-melatonin in the Syrian hamster.

Groups of adult female Syrian hamsters (Mesocricetus auratus) were injected daily at 17:00 hr with 2.5, 15, or 25 micrograms of melatonin (Mel) or 6-chloro-melatonin (Cl-Mel) for 12 weeks. An ovary from each animal was completely serially sectioned for light microscopic investigation. Judging from the presence of corpora lutea, there were some animals in each group that continued to cycle, although the postestrous, white mucous discharge had disappeared. Noncycling animals were most often found in the 25-micrograms group of Cl-Mel. Only uterine weights of noncycling animals treated with either 25 or 15 micrograms of Mel or Cl-Mel were statistically significantly depressed versus controls. Cl-Mel (25 micrograms) significantly suppressed the total number and size of antral follicles (P less than 0.05). Follicular ruptures with incomplete or complete release of the oocyte out of the follicular compartment were observed. The oocyte release occurred either into the ovary ("intraovarian oocyte release: IOR") or outside of the ovary ("extraovarian oocyte release: EOR"). Compared with controls, the total number of IOR was increased in all experimental groups with the exception of the 2.5-micrograms group of Cl-Mel. IOR appeared in both preantral and antral follicles, and often IOR was complete. In controls, only preantral follicles were involved in IOR; these were primarily incomplete ones. IOR was seen in cycling and noncycling animals. By contrast, EOR was exclusively observed in noncycling hamsters. It is concluded that the cessation of postestrous, white mucous discharge is not necessarily an index for a halt in cyclic ovarian function. Injections of 25 micrograms of Cl-Mel are more effective than 25 micrograms of Mel in suppressing ovarian function. Both Mel and Cl-Mel increase the frequency of IOR. Finally, noncycling hamsters show EOR that is regarded as an abnormal ovulation.

Animals↗

Morphological and morphometric changes in the ovaries of white-footed mice (Peromyscus leucopus) following exposure to long or short photoperiod.

Two experiments were carried out with a total of 36 white-footed mice (Peromyscus leucopus) exposed to either long (LP) or short (SP) photoperiod for six weeks. Ovaries and uteri were weighed. Serial sections of the ovaries were processed for light microscopy. The total number of the interstitial gland cells, preantral and antral follicles with early and advanced stages of atresia as well as corpora lutea, was determined. Uteri from LP mice weighed significantly more than those from SP mice in both experiments. In contrast, the weight of ovaries from LP and SP animals only differed significantly in one experiment; this experiment also produced no obvious changes in the total number of corpora lutea. While interstitial gland cells of LP ovaries were hypertrophic and appeared mature, the interstitial gland cells of SP ovaries were of the degenerating cell type. The total number of follicles as well as their mean follicular diameters were higher in LP animals in comparison with SP animals. In addition, the percentage of antral follicles were increased and there were fewer signs of advanced stages of atresia in the LP group. It is suggested that the changes of the interstitial gland cell morphology combined with alterations of follicular growth during LP or SP appear to support intensified follicular growth.

Animals↗

Inverse correlation between "synaptic" ribbon number and the density of adrenergic nerve endings in the pineal gland of various mammals.

The number of "synaptic" ribbons was inversely correlated with the density of the adrenergic nerve endings of the pineal gland compared among a diverse group of species including the fox, cat, rat, cotton rat, white-footed mouse, Djungarian hamster, ground squirrel, and chipmunk. The concentration of norepinephrine paralleled the number of adrenergic nerve terminals in the pineal glands of the cotton rat, rat, and ground squirrel, the only species in which norepinephrine concentrations were measured. The number of ribbon fields paralleled numbers of "synaptic" ribbons in all species examined. Adrenergic nerve endings were observed primarily within the perivascular spaces, although some endings also were found among parenchymal cells. Adrenergic nerve endings forming synaptic junctions with pinealocytes were not observed in any of these species, nor was there any physical association between these nerve endings and "synaptic" ribbons.

Animals↗

A possible mechanism of rapid luteolysis in white-footed mice, Peromyscus leucopus.

Adult female white-footed mice, Peromyscus leucopus, were exposed to long (LP) or short (SP) photoperiods for 6 weeks (experiment I). Another group of animals was kept for 6 weeks in SP, then injected SC with 30 micrograms prolactin twice daily for 2, 3, 4, or 6 days (experiment II). Ovaries from the mice in both experiments were weighed and serially sectioned for light microscopic examination of regressing corpora lutea. In experiment I, it was observed that vessels supporting corpora lutea were dilated, and that their endothelium was either undergoing necrosis or it was missing. Pronounced changes of luteal capillaries led to rupture and intraluteal hemorrhage, thus opening the capillary bed. Regressing luteal cells became segregated and seemed to invade the vascular system passively. They were seen as luteal cell thrombi in medullary veins. This luteolytic course termed "rapid luteolysis" was most apparent in SP ovaries. It differed from "retarded luteolysis," which represents the well-established luteolytic model of auto- and heterophagocytosis. In experiment II, there was a statistically significant decrease in ovarian weight 4 days after prolactin treatment in comparison with saline-treated controls. At the light microscopic level, signs of both rapid and retarded luteolysis were present, but not intensified. It is concluded: (1) The concept of rapid luteolysis represents a reasonable working hypothesis. (2) Prolactin, though luteolytic at the macroscopic level, failed to produce evidence of increased rapid or retarded luteolysis at the light microscopic level.

Animals↗

On the occurrence of a myeloid body in pinealocytes of the white-footed mouse, Peromyscus leucopus. An electron-microscopic study.

The fine-structural features of pinealocytes of the white-footed mouse, Peromyscus leucopus, were examined. A single population of pinealocytes was observed in both superficial and deep components of the gland. Cells in both locations are characterized by the presence of an indented nucleus exhibiting a prominent nucleolus. The usual organelles in the perikaryon are the Golgi complexes, mitochondria, endoplasmic reticulum, polysomes, microtubules and dense-core vesicles. In addition the perikaryonal cytoplasm often contains a single myeloid body. These bodies are usually lenticular in shape, are formed of an array of flattened membranous cisternae, and are not bounded by a limiting membrane. This organelle usually lies in the vicinity of the nucleus and is infrequently associated with lipid bodies. Complex forms were also observed. The cisternae are continuous with elements of the endoplasmic reticulum at points along their expanded rims. The outer surface of the cisternal membrane exhibits a granularity or fuzziness. The cisternae may be fenestrated. Pinealocyte processes with an abundance of clear vesicles, and some dense-core vesicles and vesicle-crowned rodlets are present in the parenchyma.

Animals↗