Biomedical subjects

K A Stokkan

Publications and source records attributed to K A Stokkan.

At least 19 recordsLinked to original sources

PubMed2001

Entrainment of the circadian clock in the liver by feeding.

Circadian rhythms of behavior are driven by oscillators in the brain that are coupled to the environmental light cycle. Circadian rhythms of gene expression occur widely in peripheral organs. It is unclear how these multiple rhythms are coupled together to form a coherent system. To study such coupling, we investigated the effects of cycles of food availability (which exert powerful entraining effects on behavior) on the rhythms of gene expression in the liver, lung, and suprachiasmatic nucleus (SCN). We used a transgenic rat model whose tissues express luciferase in vitro. Although rhythmicity in the SCN remained phase-locked to the light-dark cycle, restricted feeding rapidly entrained the liver, shifting its rhythm by 10 hours within 2 days. Our results demonstrate that feeding cycles can entrain the liver independently of the SCN and the light cycle, and they suggest the need to reexamine the mammalian circadian hierarchy. They also raise the possibility that peripheral circadian oscillators like those in the liver may be coupled to the SCN primarily through rhythmic behavior, such as feeding.

Animals↗

PubMed2001

Melatonin potentiates the vasoconstrictive effect of noradrenaline in renal artery from newborn hooded seals (Cystophora cristata) and harp seals (Phoca groenlandica).

Isometric tension was recorded by force displacement transducers in ring segments of the inferior branch of the renal artery from newborn hooded seals (Cystophora cristata, n=6), harp seals (Phoca groenlandica, n=3) and domestic pigs (Sus scrofa f. domestica, n=5). Arterial segments were mounted in heated organ baths and exposed to graded concentrations of noradrenaline (NA) and adrenaline (A), alone or together with melatonin. The melatonin concentration in the bath was similar to the plasma concentration normally found in each experimental animal. Melatonin alone did not affect the tension in any of the species, but melatonin potentiated the contraction induced by NA in hooded and harp seal arteries to a maximum of about 25% above the resting, pre-stretch level. The selective melatonin receptor antagonist luzindole reduced this potentiation by 80%. Species-specific concentrations of melatonin did not potentiate the NA-effect in the domestic pig or the A-induced contraction in any of the species. The results indicate that melatonin specifically increases the NA-sensitivity of smooth muscles in renal arteries from newborn seals. It is presumed that similar effects may operate in foetal and maternal seals and may influence their circulation during maternal diving.

Animals↗

PubMed1999

Seasonal and daily variations in plasma melatonin in the high-arctic Svalbard ptarmigan (Lagopus mutus hyperboreus).

This study presents the daily rhythm of melatonin secretion throughout one year in a bird from the northern hemisphere, the Svalbard ptarmigan (Lagopus mutus hyperboreus), which lives naturally at 76-80 degrees N. Eight Svalbard ptarmigan were caged outdoors at 70 degrees N and blood sampled throughout one day each month for 13 months. At this latitude, daylight is continuous between May and August, but there is a short period of civil twilight around noon from late November to mid January. There was no daily rhythm in plasma melatonin in May-July. Plasma melatonin levels varied significantly throughout the day in all other months of the year, with the nighttime increase reflecting the duration of darkness. The highest mean plasma concentration occurred at midnight in March (110.1 +/- 16.5 pg/ml) and represented the annual peak in estimated daily production. Around the winter solstice, melatonin levels were significantly reduced at noon and elevated during the nearly 18 h of consecutive darkness, and the estimated mean daily production of melatonin was significantly reduced. Thus, at the times of the year characterized by light-dark cycles, melatonin may convey information concerning the length of the day and, therefore, progression of season. The nearly undetectable low melatonin secretion in summer and the reduced amplitude and production in midwinter indicate a flexible circadian system that may reflect an important adaptation to life in the Arctic.

Animals↗

PubMed1998

Dual entrainment by light and food in the Svalbard ptarmigan (Lagopus mutus hyperboreus).

The possibility that feeding may act as a zeitgeber has been investigated in captive Svalbard ptarmigan by recording feeding or food-searching activity (FA) in birds given periodic access to food (PAF) under light-dark (LD) cycles or in continuous bright (LL) or dim light (DD) conditions. Except during LL, anticipatory attempts to feed always occurred prior to the food access interval with a relatively stable phase relationship to the interval. There was always a second bout of feeding toward the end of the food access interval, which apparently corresponds to the afternoon bout of feeding, seen under LD and ad libitum access to food. During PAF, this afternoon peak of activity disappeared. When the LD cycle was phase delayed while restricted access to food remained unchanged, the afternoon peak of feeding was temporarily reestablished but was transiently shifted forward to reattain its position within the food access interval. After termination of PAF, the afternoon bout of feeding was reestablished through phase-delaying transients, with an initial phase corresponding to the previous food access interval. The results suggest that FA of Svalbard ptarmigan is controlled by 2 separate circadian oscillators, both of which can be entrained by light and food: a putative morning oscillator, which controls the activity associated with the beginning of the photoperiod or the food access interval, and a putative evening oscillator, which induces increased activity toward the end of these intervals. In their natural environment at very high latitudes, Svalbard ptarmigan deposit fat when the day length declines rapidly in autumn. Entrained by feeding, they appear to enjoy a longer daily period of food-searching activity than if day length was the only zeitgeber.

Animal Feed↗

PubMed1995

Pineal and thyroid functions in newborn seals.

Daily variations of pineal and plasma melatonin and plasma thyroid hormones were measured in harp seals (Phoca groenlandica), grey seals (Halichoerus grypus), and hooded seals (Cystophora cristata), ranging in age from newborn to 14 days. In newborn harp seals the mean mass of the pineal gland was 273 mg (+/- 45 SEM, n = 11), containing 49 ng (median) melatonin. In newborn, 4- and 10-day-old grey seals, the pineal mass was similar, weighing on average 337 mg (+/- 74, n = 6) and containing 90 ng melatonin. Two newborn hooded seal pups had pineals weighing 520 and 1289 mg, with 254 and 7600 ng melatonin, respectively. There were no day-night differences in the pineal contents of melatonin or in the number of pineal beta-adrenergic receptors measured in newborn harp seals, and, in newborn, 4- and 10-day-old grey seals, there were no day-night or age differences in pineal melatonin content. Plasma melatonin levels were 10 times higher in newborn seals than in two 10-day-old grey seals and one 14-day-old harp seal pup. In all seal pups, the levels exhibited a 24-hr rhythmicity, with increasing night- and decreasing daytime concentrations. Plasma levels of thyroxine (T4) and triiodothyronine (T3) were generally higher in newborn seals than in 10- and 14-day-old seals or in adult females. There was no apparent 24-hr rhythmicity, but the thyroid hormone levels generally declined throughout each sampling sequence. High pineal and thyroid activities may play a thermoregulatory role in newborn seals, but the results do not indicate a stimulatory action of melatonin in the peripheral conversion of T4 to T3. It is speculated that the large and active pineal gland, particularly in newborn seals, may be related to aspects of their diving habit.

Aging↗

PubMed1994

Melatonin rhythms in Arctic urban residents.

The 24-hr rhythm of salivary melatonin was measured in persons living in the city of Tromsø (70 degrees N) at the following times of the year: in January at a day length of 2 hr of twilight, in June under continuous sunshine, and in March and September at about 12 hr light and 12 hr darkness. The hormone patterns varied widely between individuals, but, in general, they were consistent within most individuals between the seasons. Highest peak values occurred in January when the mean level was also significantly higher than at any other time of year. The lowest mean levels occurred in June. Although individual rhythms were not always apparent, the mean patterns showed significantly elevated melatonin concentrations during the night at all seasons. The June melatonin peak was similar to that in March and September, but appeared to be phase-delayed with increased melatonin concentrations from midnight until 0900. It is assumed that the delayed melatonin peak in June may be associated with a tendency among people to shift their activity/rest rhythm and that the pineal sensitivity to light is reduced in the morning in summer.

Adult↗

PubMed1993

Photoperiodic adaptation to breeding at different latitudes in great tits.

The photoperiodic responses in testicular growth and plasma levels of LH in nonmigratory great tits from Tromsö, Norway (69 degrees 40'N), Göteborg, Sweden (57 degrees 42'N), and Milano, Italy (45 degrees 26'N) were compared under the same lighting conditions. Male great tits, collected during midwinter, were transferred to Göteborg, and shifted from an 8-hr day in early January to a lighting regime in which day length was increased by 1/2 hr per week for 16 weeks. Control birds (only from Sweden) were kept on a 8L:16D light regime during the entire study. Blood samples were collected weekly, and laparotomies were performed every other week. Initially testicular size (approximately 1.6 mm) and plasma levels of LH (approximately 0.45 ng/ml) were similar among the four groups. Between 4 and 8 weeks after the onset of the experiment testes gradually, but significantly, increased to about 2 mm in length in the control group. This slow growth was also observed in the experimental groups. The control bird testes did not increase in size any further. The onset of the rapid testicular growth phase differed among the three experimental groups. In great tits from Milano it began when day length exceeded 11 hr; in birds from Tromsö, when day length was greater than 12 hr; and in great tits from Göteborg, when day length was between 11 and 12 hr. Once the rapid gonadal growth phase had begun it took about 6 weeks for the testes to reach maximal size (approximately 6.8 mm) in all three populations.(ABSTRACT TRUNCATED AT 250 WORDS)

Acclimatization↗

PubMed1993

Type II iodothyronine 5'-deiodinase in mouse brown adipose tissue is stimulated by a single injection of isoproterenol in an oil/water emulsion.

A single subcutaneous morning injection of the beta-adrenergic agonist isoproterenol (ISO) (10 mg/kg body weight) in an oil/water emulsion (70/30; v/v) caused a marked increase in the activity of the enzyme type II iodothyronine 5'-deiodinase (5'-D II) in the interscapular brown adipose tissue of BDF-1 mice. After a delay of 4 hours, the 5'-D II activity began to rise in an almost linear fashion and was increased 3-fold after 8 hours, when compared to the control values. The results indicate that this method of ISO administration may be a valid tool for artificial stimulation of brown adipose tissue in animals by beta-adrenergic agonists.

Adipose Tissue, Brown↗

PubMed1991

Food restriction retards aging of the pineal gland.

The effects of chronic (40%) food restriction from 6 weeks of age were studied in aging male Fisher 344 rats. When compared with 3-month-old, ad libitum fed rats, pineal N-acetyltransferase (NAT) activity had declined to less than 30% and pineal and serum levels of melatonin to 40% after 28 months when feeding had been ad libitum. Food restriction significantly retarded this development (P less than 0.05) giving NAT and melatonin levels which were twice as high as in the ad libitum fed group. Nighttime levels of pineal serotonin (5-HT) were similar in food-restricted and ad libitum fed old rats but were nearly twice as high (P less than 0.05) as in young rats. There was also a tendency for increased production of 5-hydroxyindoleacetic acid (5-HIAA) in the pineal gland with higher levels of 5-HT. It is concluded that aging in the rat (Fisher 344) is accompanied by a reduction of pineal NAT activity, thereby reducing the production of melatonin and causing a buildup of 5-HT in the pineal gland. It is furthermore proposed that food restriction, which markedly increases the life span and reduces age-related physiological deterioration and diseases in many animals, may mediate some of its effects through a sustained pineal activity in old age.

Aging↗

PubMed1991

Evidence that extremely low frequency Ca(2+)-cyclotron resonance depresses pineal melatonin synthesis in vitro.

The effects of ion cyclotron resonance (ICR)-type magnetic fields on pineal glands were investigated. Both the synthesis and the release of pineal melatonin, the gland's major hormone, were significantly (P less than 0.001 in each case) reduced by Ca(2+)-ICR-exposure, presumably caused by a reduced activity (P less than 0.05) of the enzyme N-acetyltransferase. It is concluded that this type of exposure may help to explain some of the effects of electromagnetic fields on biological systems. An extension to the existing ICR theory is presented which explains that ICR-like conditions may occur under various environmental circumstances.

Animals↗

PubMed1991

Evidence that interferon-gamma alters pineal metabolism both indirectly via sympathetic nerves and directly on the pinealocytes.

1. Interferon-gamma (IFN-gamma) has been shown to suppress N-acetyltransferase (NAT) activity in cultured rat pineal glands when stimulated with isoproterenol (ISO). 2. Conversely, IFN-gamma has also been shown to increase the melatonin content of the rat pineal gland in organ culture. 3. Circumstantial evidence leads to a hypothesis that the NAT suppressive effect may be due to the action of IFN-gamma on the sympathetic nerve terminals. 4. To test this hypothesis, pineal glands from intact (INT) and superior cervical ganglionectomized (SCGX) rats, which had been operated 5 days earlier, were cultured with either ISO or ISO + IFN-gamma. 5. The concentration of ISO was 10(-8) M and that of IFN-gamma was 300 antiviral units/ml. 6. The pineals were incubated for a total period of 5.5 hr, after which the activities of NAT and hydroxyindole-O-methyltransferase (HIOMT) and the levels of melatonin and cAMP were estimated. 7. Suppression of NAT by IFN-gamma was observed in the pineals from INT rats, but not in those from SCGX animals. 8. IFN-gamma significantly enhanced melatonin levels over those in ISO-stimulated pineals and culture media from the SCGX animals, but not from the INT animals. 9. IFN-gamma treatment had no effect on either the HIOMT activity or cAMP levels. 10. The results indicate that the IFN-gamma-induced NAT suppression requires the integrity of the sympathetic nerve terminals and the IFN-gamma-induced enhancement of melatonin production is accomplished through its direct action on pinealocytes.

Acetylserotonin O-Methyltransferase↗

PubMed1991

Parathion (O,O-dimethyl-O-p-nitrophenyl phosphorothioate) induces pineal melatonin synthesis at night.

The effects of parathion on male rat pineal N-acetyltransferase (NAT) activity, hydroxyindole-O-methyltransferase (HIOMT) activity and pineal and serum melatonin levels at the end of light period (2000 h) and at night (2300 h and 0100 h) were studied. Additionally, pineal levels of 5-hydroxytryptophan (5-HTP), serotonin (5-HT), and 5-hydroxyindole acetic acid (5-HIAA) were estimated. Parathion was administered intragastrically at total doses (over 6 days) of either 6.5 or 13 mg/kg. Control rats received vehicle (corn oil) only. During the study, the rats were exposed to light:dark cycles of 14:10 with light off at 2100 h. Pineal NAT activity was increased at 0100 h following parathion administration at both doses, but HIOMT activity was unaffected. Pineal and serum melatonin levels were increased at night (2300 h and 0100 h) after the 13 mg/kg dose of parathion while the lower dose increased pineal melatonin only at 0100 h. Also, both doses decreased 5-HTP at 2000 h while the lower dose increased it at 2300; 5-HT was significantly decreased at 2300 h and 5-HIAA levels were lower but only significantly so for the 13 mg/kg dose at 2000 h. The results indicate that parathion has significant effects on pineal melatonin synthesis by mechanisms which remain unknown.

Acetylserotonin O-Methyltransferase↗

PubMed1991

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↗

PubMed1991

Adenosine effects on the rat pineal gland in vitro: cyclic adenosine monophosphate levels, N-acetyltransferase, and thyroxine type II 5'-deiodinase activities and melatonin production.

The presence of adenosine and its receptors in the pineal gland suggests that they could have a regulatory influence on pineal physiology. Rat pineal glands cultured in the presence of the adenosine analog 5'-N-ethylcarboxamido adenosine (NECA) promoted a significant increase in pineal adenosine 3'5'-monophosphate (cAMP) content, similar to that caused by the beta-adrenergic receptor agonist isoproterenol (ISO). A potentiation of the cAMP response occurred when the glands were simultaneously stimulated with both NECA and ISO. Whereas high cAMP levels induced by ISO were associated with an increased N-acetyltransferase (NAT) activity and rise in the melatonin production and release, the NECA-induced rise in cAMP concentration failed to promote an increase in the activity of either NAT or another pineal enzyme thyroxine 5'-deiodinase type II; likewise, pineal melatonin levels did not rise.

Adenosine↗

PubMed1991

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↗

PubMed1990

Marked rapid alterations in nocturnal pineal serotonin metabolism in mice and rats exposed to weak intermittent magnetic fields.

Adult AMES mice and male Sprague Dawley rats were exposed to an artificial magnetic field, generated by Helmholtz coils. 3.5 hours after the onset of darkness the coils were activated for one hour resulting in an inversion of the horizontal component of the earth's magnetic field. The coils were activated and deactivated at 5 min intervals during the 1 hour exposure period. In both mice and rats, the levels of serotonin in the pineal were markedly increased by the exposure. In rats, an increase of pineal 5-hydroxyindole acetic acid and a decrease of the activity of the pineal enzyme serotonin-N-acetyltransferase also was observed. However, pineal and serum melatonin levels were not altered. The results indicate that the metabolism of serotonin in the pineal is quickly affected by the exposure of animals to a magnetic field.

Animals↗

PubMed1988

Endocrine changes in photostimulated willow ptarmigan (Lagopus lagopus lagopus) and Svalbard ptarmigan (Lagopus mutus hyperboreus).

Changes in plasma luteinizing hormone (LH), testosterone, thyroxine (T4), and triiodothyronine (T3) and the height of supraorbital combs were compared in captive willow ptarmigan (Lagopus lagopus lagopus) and Svalbard ptarmigan (Lagopus mutus hyperboreus) exposed to an artificial annual cycle of daylength simulating that at 70 degrees N. Plasma LH and testosterone and comb height increased more slowly in Svalbard than in willow ptarmigan as daylength increased. In both species, plasma LH and testosterone fell abruptly, and the supraorbital combs regressed in June, marking the development of long-day refractoriness. Comparison with free-living Svalbard ptarmigan (K.-A. Stokkan, P. J. Sharp, and S. Unander (1986) Gen. Comp. Endocrinol. 61, 446-451) at 80 degrees N, showed a similar slow increase in reproductive function before the onset of the breeding season. However, maximum plasma LH levels and comb size were higher in free-living than in captive Svalbard ptarmigan. Furthermore, long-day refractoriness developed earlier in captive than in free-living Svalbard ptarmigan. In both species of ptarmigan, the development of long-day refractoriness was associated with increased plasma prolactin. This increase was larger and occurred earlier in the Svalbard than in the willow ptarmigan. Seasonal changes in thyroid hormones were not as marked as for the other hormones measured. In both species, plasma T4 tended to increase and plasma T3 to decrease as daylength increased. A small increase in plasma T3 was seen after the development of long-day refractoriness in both species. It is concluded that captivity depresses the photoperiodic response of Svalbard ptarmigan more than that of willow ptarmigan.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

The annual breeding cycle of the high-arctic Svalbard ptarmigan (Lagopus mutus hyperboreus).

Gonadal size, spermatogenesis, egg production, height of the supraorbital comb, moult, and plasma luteinizing hormone (LH) levels were measured during an annual cycle in wild Svalbard ptarmigans (Lagopus mutus hyperboreus). These birds live permanently at 77-81 degrees N where daylight is continuous from the beginning of April until mid September while the average ambient temperature is above freezing only between early June and mid September. The gonads and comb size began to enlarge in March coinciding with an increase in plasma LH, but sperm production and egg laying did not begin until the end of May and early June, respectively. This long lag between the onset of reproductive functions and the time of breeding reflects a slow rate of gonadal growth which may be caused by nonphotoperiodic, inhibitory input from the environment. Gonadal regression occurred in July and was associated with a steep decline in plasma LH levels indicating that the birds became long-day refractory. A moult from white to pigmented plumage occurred in females at the beginning and in males towards the end of the breeding season. This observation is consistent with the notion of an inhibitory effect of testosterone on moult in the males. Both sexes moulted simultaneously into white plumage in late September/early October.

Animals↗