Search PubMed⌕ Search

Biomedical subjects

I Zucker

Publications and source records attributed to I Zucker.

At least 19 recordsLinked to original sources

Termination of neuroendocrine refractoriness to melatonin in Siberian hamsters (Phodopus sungorus).

Siberian hamsters maintained from birth in a short day length (DL), unlike their long-day counterparts, fail to undergo reproductive development by 5 weeks of age. Instead, reproductive maturation of short-day males is delayed for approximately 20 weeks, at which point neuroendocrine refractoriness to the inhibitory effects of short DLs develops, resulting in growth of the gonads. To terminate refractoriness and re-establish responsiveness to short photoperiods, 10-15 weeks of long-day exposure is required. We assessed whether continuous exposure to long days is necessary to terminate refractoriness or whether the first few weeks of long days initiate a process that culminates several months later in the breaking of refractoriness. Male hamsters refractory to short DLs were transferred to a long-day photoperiod, pinealectomized (PINx) after 0, 3, 6 or 15 weeks, and subsequently infused for 6 weeks with a short-day melatonin signal. This melatonin treatment induces gonadal regression in photosensitive but not in photorefractory hamsters. Six percent of males PINx at week 0 and 88% of those PINx at week 15 underwent gonadal atrophy by the end of the melatonin infusion treatment initiated on week 15. Among hamsters PINx on week 6, 17% versus 76% underwent testicular involution in response to melatonin infusions initiated on week 6 and week 15, respectively. This finding indicates that a fraction of the long days that hamsters experience during spring and summer are sufficient to trigger the processes that restore responsiveness to short DLs. Additional groups of pineal-intact photorefractory animals were given 3, 6 or 15 weeks of long-day exposure and then returned to a short DL for several months; only those treated for 15 weeks terminated refractoriness. The breaking of refractoriness, once triggered by long-day melatonin signals, proceeds to completion only in the absence of short-day melatonin signals.

Animals↗

Seasonal control of penile development of Siberian hamsters (Phodopus sungorus) by daylength and testicular hormones.

Seasonal variation in prepubertal penile growth has not previously been studied. The present study assessed the influence of daylength and androgens on penile development in the Siberian hamster (Phodopus sungorus). Adult penile masses were achieved at 18 and 8 weeks of age in hamsters maintained from birth under short (10 h light:14 h dark) versus long (14 h light:10 h dark) daylengths, respectively. Insulin-like growth factor I concentrations, previously implicated in penile growth, did not differ between hamsters maintained in short versus long daylengths. Gonadectomized juvenile males maintained in short and long daylengths and administered testosterone attained adult penile masses well in advance of untreated gonad-intact males maintained in short daylengths. Hamsters from both photoperiods, castrated as juveniles and first treated with testosterone in adulthood, also achieved adult penile masses. The photoinhibited gonad is insufficient to promote penile growth, and prepubertal gonadal secretions during short daylengths are not necessary for eventual penile development. Among young born near the end of the mating season, onset of neuroendocrine refractoriness to short daylengths at about 100 days of age and subsequent gonadal development induces growth in all reproductive tissues. Timing of puberty and increased androgen secretion controlled by daylength are the primary determinants of postnatal penile growth, which may also be affected by prenatal and early postnatal organizational actions of androgens.

Animals↗

Photoperiodic control of oestrous cycles in Syrian hamsters: mediation by the mediobasal hypothalamus.

To assess whether the mediobasal hypothalamus (MBH) is necessary for photoperiodic control of oestrous cycles and prolactin secretion, we tested intact female Syrian hamsters (controls) and those that had sustained unilateral or bilateral lesions of the MBH. All hamsters displayed 4-day oestrous cycles postoperatively in the long-day photoperiod (14 h light/day); control females and those with unilateral MBH damage ceased to undergo oestrous cycles approximately 8 weeks after transfer to a short-day photocycle (10 h light/day), whereas 12 of 15 females with bilateral MBH lesions continued to generate 4-day oestrous cycles throughout 22 weeks in short days. Serum prolactin concentrations were either undetectable or low in all hamsters 8 or 14 weeks after the transfer to short-day lengths, but increased above long-day baseline values by week 22. We conclude that melatonin-binding sites in the MBH mediate suppression of oestrous cycles but not prolactin secretion by short-day lengths; recovery of prolactin secretion in females during prolonged exposure to short-day lengths reflects development of refractoriness to melatonin in a substrate distinct from the MBH. These findings suggest that separate neural pathways mediate photoperiodic control of gonadotropin and prolactin secretion in female hamsters.

Animals↗

Itch characteristics in Chinese patients with atopic dermatitis using a new questionnaire for the assessment of pruritus.

BACKGROUND: Although pruritus is the predominant and commonest feature of atopic dermatitis, its clinical characteristics have not been explored. OBJECTIVE: To characterize the clinical pattern and sensory and affective dimensions of the itch experience utilizing a comprehensive itch questionnaire. METHODS: A structured itch questionnaire based on the McGill pain questionnaire was given to 102 Chinese patients with known atopic dermatitis. RESULTS: There were 100 patients with atopic dermatitis who fully filled the questionnaire. In 87% of the patients pruritus appeared on a daily basis. It had a prolonged duration (mean duration 10.7 7.3 years). It involved all body areas mostly in the lower limbs (83%), flexures (76%), upper limbs (71%) and neck (65%). Itch intensity during its peak was nearly twice higher than the itch of a mosquito bite. Itching was most frequent at night (65%), and 84% of patients reported of difficulty falling asleep. Daily life activities which increased the severity of itch were sweat in 96%, dryness in 71%, stress in 71% and physical effort in 73%. The major factors which were found to reduce the intensity of pruritus included: bathing with cold water in 55% and cold ambient environment in 56%. Associated symptoms were heat sensation (51%), sweating (40%) and pain in the pruritic area (45%). The various anti-pruritic therapies had limited long-term effect. The pruritus was bothersome (52%) and a major distress to the patient. The affective score correlated to itch intensity during its peak (r = 0.4, P < 0.001). CONCLUSIONS: The study provided a detailed description of pruritus in atopic dermatitis with new data on affective and sensory dimensions and associated symptoms. The questionnaire was found to be a useful tool in characterization of itch.

Adolescent↗

Refractoriness to melatonin occurs independently at multiple brain sites in Siberian hamsters.

The mid-winter development of refractoriness to melatonin (Mel) triggers recrudescence of the atrophied reproductive apparatus of rodents. As a consequence, over-wintering animals become reproductively competent just before the onset of spring conditions favorable for breeding. The neural target tissues that cease to respond to winter Mel signals have not been identified. We now report that the suprachiasmatic nucleus of the hypothalamus, which contains the principal circadian clock, and the reuniens and paraventricular nuclei of the thalamus, each independently becomes refractory to melatonin. Small implants of Mel that were left in place for 40 wk and that act locally on these brain nuclei, induced testicular regression within 6 wk in male Siberian hamsters; 12 wk later Mel implants no longer suppressed reproduction and gonadal recrudescence ensued. Hamsters that were then given a systemic Mel infusion s.c. immediately initiated a second gonadal regression, implying that neurons at each site become refractory to Mel without compromising responsiveness of other Mel target tissues. Refractoriness occurs locally and independently at each neural target tissue, rather than in a separate "refractoriness" substrate. Restricted, target-specific actions of Mel are consistent with the independent regulation by day length of the several behavioral and physiological traits that vary seasonally in mammals.

Animals↗

A questionnaire for the assessment of pruritus: validation in uremic patients.

A questionnaire was constructed for the evaluation and measurement of pruritus. The questionnaire, based on the short form of the McGill Pain Questionnaire, was tested in 145 patients suffering from uremic pruritus and currently undergoing hemodialysis treatment in 3 centers. The newly developed questionnaire proved to be reliable and provided valid data on the sensory, affective and overall intensity of uremic pruritus. The data suggest that uremic pruritus tends to be prolonged, frequently intense and a major source of distress to the patient. Dialysis was not found to influence the pruritus. The questionnaire may also be useful in pruritus secondary to other causes.

Adult↗

Energy intake and fur in summer- and winter-acclimated Siberian hamsters (Phodopus sungorus).

Few studies have directly addressed the impact of fur on seasonal changes in energy intake. The daily food intake of Siberian hamsters (Phodopus sungorus) was measured under simulated summer and winter conditions in intact animals and those with varying amounts of pelage removed. Energy intake increased up to 44% above baseline control values for approximately 2-3 wk after complete shaving. Increases in food intake varied with condition and were greater in hamsters housed in short than long day lengths and at low (5 degrees C) than moderate (23 degrees C) ambient temperatures. Removal of 8 cm(2) of dorsal fur, equivalent to 30% of the total dorsal fur surface, increased food intake, but removal of 4 cm(2) had no effect. An 8-cm(2) fur extirpation from the ventral surface did not increase food consumption. Food intake was not influenced differentially by fur removal from above brown adipose tissue hot spots. Fur plays a greater role in energy balance in winter- than summer-acclimated hamsters and conserves energy under a wide range of environmental conditions.

Acclimatization↗

Low ambient temperature accelerates short-day responses in Siberian hamsters by altering responsiveness to melatonin.

Exposure to low ambient temperatures (Ta) accelerates appearance of the winter phenotype in Siberian hamsters transferred from long to short day lengths. Because melatonin transduces the effects of day length on the neuroendocrine axis, the authors assessed whether low Ta promotes the transition to winterlike traits by accelerating the onset of increased nocturnal melatonin secretion or by enhancing responsiveness to melatonin in short day lengths. Male hamsters were transferred from 16L (16 h light/day) to 8L (8 h light/day) photoperiods and held at 5 degrees C or 22 degrees C. Locomotor activity was recorded continuously, and body mass, testis size, and pelage color were determined biweekly for 8 weeks. The duration of nocturnal locomotion (alpha), a reliable indicator of the duration of nocturnal melatonin secretion, lengthened significantly earlier in hamsters exposed to a Ta of 5 degrees C than 22 degrees C. Cold exposure increased the proportion of hamsters that were photoresponsive: gonadal regression in short days increased from 44% at 22 degrees C to 81% at 5 degrees C (p < 0.05); low Ta did not, however, accelerate testicular regression in animals that were photoresponsive. Nonphotoresponsive animals at 5 degrees C temporarily had longer alphas during the first 4 weeks in short days and significant decreases in body mass and testicular size that were reversed during the ensuing weeks when alpha decreased. In a 2nd experiment, pinealectomized male hamsters infused for 10 h/day with melatonin for 2 weeks had significantly lower body and testes masses when maintained at 5 degrees C but not 22 degrees C. Low-ambient temperature appears to accelerate the appearance of the winter phenotype primarily by increasing target tissue responsiveness to melatonin and to a lesser extent by augmenting the rate at which the duration of nocturnal melatonin secretion increases in short day lengths.

Analysis of Variance↗

Establishment and persistence of photoperiodic memory in hamsters.

Long summer days unequivocally stimulate, and short winter days inhibit reproduction in Siberian hamsters. By contrast, intermediate-duration day lengths (12.5-14 h long) either accelerate reproductive development or initiate regression of the reproductive apparatus. Which of these outcomes transpires depends on an animal's photoperiodic history, suggesting that hamsters must encode a representation of prior photoperiods. The duration of nocturnal melatonin secretion is the endocrine representation of day length, but nothing is known about how long it takes to establish photoperiodic histories or how long they endure. Hamsters exposed for 2 or more weeks to long summer day lengths acquired a long-day photoperiodic history that determined subsequent reproductive responses to intermediate-duration day lengths and melatonin signals. The memory for long-day lengths persisted in pinealectomized hamsters for 6.5 weeks, faded significantly after 13 weeks, and was functionally absent after 20 weeks. These findings indicate that hamsters are influenced only by relatively recent day lengths and melatonin signals and ignore earlier ones that might cause them to misinterpret the salience of current day lengths.

Analysis of Variance↗

Triggering of neuroendocrine refractoriness to short-day patterns of melatonin in Siberian hamsters.

Short day lengths induce gonadal regression within 6 weeks in Siberian hamsters, but this inhibitory effect eventually wanes and reproductive competence is regained after 4-6 months in short days. These experiments were undertaken to determine whether continuous exposure to short days for several months is necessary to induce neuroendocrine refractoriness, or if a few weeks of short days are sufficient to trigger processes that culminate in refractoriness several months later. Adult male Siberian hamsters transferred from their natal long-day photoperiod of 15L (15 h light/day) to a short-day photoperiod of 10L were pinealectomized (PINx) after 0, 6, 12, 21 or 40 weeks of exposure to 10L. Intact hamsters kept in 10L manifested gonadal regression by week 6 and completed gonadal recrudescence by week 40, at which time they too were PINx. Beginning at week 40 all hamsters were infused s.c. with melatonin for 10 h/day for 6 consecutive weeks. This treatment induces gonadal regression in photosensitive hamsters. At the end of melatonin treatment, maximal gonadal regression was recorded for hamsters PINx at week 0 and those PINx after 40 weeks in long days. Hamsters PINx after 40 week of short day treatment were completely unresponsive to melatonin whereas those PINx after 6 and 12 weeks had intermediate responses. The percentage of hamsters whose reproductive apparatus was refractory to melatonin at week 40 increased with increasing duration of exposure to short days prior to PINx. Refractoriness was induced by relatively few weeks of short days in some hamsters, whereas others required much more extensive exposure. Induction of refractoriness is triggered by a fraction of the short days that hamsters experience in nature but may not be manifested until many weeks later when it coincides with gonadal recrudescence. In nature all hamsters are exposed to short days for at least 25 weeks, ensuring refractoriness in most individuals.

Animals↗

Role of area postrema in control of torpor in Siberian hamsters.

Siberian hamsters undergo torpor during the short days of winter and in response to glucoprivation or food restriction. We tested whether the area postrema and the adjacent nucleus of the solitary tract (hereafter the AP), which monitor metabolic fuel availability, also control the onset of torpor. Siberian hamsters that had manifested torpor spontaneously or had entered torpor in response to 2-deoxy-D-glucose (2-DG) treatment were subjected to area postrema ablations (APx). Hamsters continued to display torpor postoperatively; most features of torpor were unaffected by APx. The AP is not necessary for expression of torpor elicited by short day lengths or metabolic challenge. In contrast, decreases in food intake manifested by hamsters treated with 2-DG were counteracted by APx. In Siberian hamsters, the AP appears to mediate effects of 2-DG on food intake but not torpor.

Animals↗

Testicular development in Siberian hamsters depends on frequency and pattern of melatonin signals.

We investigated the impact of frequency and pattern of melatonin signals on reproductive development in Siberian hamsters. Juvenile males gestated in short day lengths and housed in constant illumination to suppress melatonin secretion were infused with melatonin for 5 h either once or twice per day for 20 days. Melatonin infusions at either frequency produced equivalent increases in testes and body weights that exceeded those of animals infused with saline but were indistinguishable from those of hamsters transferred to long day lengths. The reproductive system appears to be maximally stimulated by a single short melatonin signal each day. Other animals kept from birth in a short photoperiod were treated 6 h after onset of darkness with the beta-adrenergic receptor antagonist DL-propranolol to shorten melatonin secretion on the night of injection but not on subsequent nights. This permitted interpolation of short nightly melatonin signals of 4-5 h duration against a background of long melatonin signals of 10-12 h duration on other nights. Treatment regimes that maintained a 1:1 ratio of short to long melatonin signals for 8 wk stimulated reproductive development; a 1:2 signal ratio, in each of three different patterns, was uniformly ineffective. The number of successive short melatonin signals had little influence on the interval across which successive melatonin signals were summated to influence photoperiodic traits. The neuroendocrine axis appears more responsive to short melatonin signal frequency than pattern for development of the summer phenotype.

Animals↗

Temperature-independence of circannual variations in circadian rhythms of golden-mantled ground squirrels.

In golden-mantled ground squirrels, phase angles of entrainment of circadian locomotor activity to a fixed light-dark cycle differ markedly between subjective summer and winter. A change in ambient temperature affects entrainment only during subjective winter when it also produces pronounced effects on body temperature (Tb). It was previously proposed that variations in Tb are causally related to the circannual rhythm in circadian entrainment. To test this hypothesis, wheel-running activity and Tb were monitored for 12 to 14 months in castrated male ground squirrels housed in a 14:10 LD photocycle at 21 degrees C. Animals were treated with testosterone implants that eliminated hibernation and prevented the marked winter decline in Tb; these squirrels manifested circannual changes in circadian entrainment indistinguishable from those of untreated animals. Both groups exhibited pronounced changes in phase angle and alpha of circadian wheel-running and Tb rhythms. Seasonal variation in Tb is not necessary for circannual changes in circadian organization of golden-mantled ground squirrels.

Animals↗

Photic entrainment of circannual rhythms in golden-mantled ground squirrels: role of the pineal gland.

Entrainment of circannual rhythms of body mass and reproduction was monitored for 3 years in female golden-mantled ground squirrels maintained in a simulated natural photoperiod. Both pinealectomized and pineal-intact squirrels generated circannual rhythms of body mass and estrus, but only the intact animals entrained these rhythms to a period of 365 days. In the second and third years after treatment, the period of the body mass rhythm was significantly shorter than 365 days for pinealectomized squirrels, and variance in tau among these animals was significantly greater than for intact squirrels. A similar pattern was evident in the rhythm of reproduction, which was phase-disrupted in pinealectomized squirrels but entrained in intacts. Seasonal changes in duration of nocturnal melatonin secretion by the pineal appear to be necessary to produce phase-delays required to entrain the circannual clock to a period of 12 months.

Animals↗

Photoperiod modulates torpor and food intake in Siberian hamsters challenged with metabolic inhibitors.

Siberian hamsters, Phodopus sungorus, exposed to a short photoperiod (SP) were challenged with 2-deoxy-D-glucose (2DG), which disrupts glycolysis and induces torpor in animals maintained in long photoperiods (LP), or mercaptoacetate (MA), which disrupts fatty acid oxidation. SP decreased rather than facilitated the induction of torpor by 2DG; decreased torpor in response to 2DG coincided with onset of spontaneous torpor in SP hamsters. In contrast, MA induced hypothermia in hamsters kept in SP but not LP, but did not induce full torpor. We conclude that short day lengths do not induce spontaneous torpor by increasing responsiveness to glucose availability; instead, responsiveness to glucoprivation is, if anything, blunted in SP. The occurrence of spontaneous torpor may be unrelated to concurrent metabolic fuel availability. Although 2DG and MA had different effects on thermoregulation in short vs. long day lengths, each treatment decreased 24-h food intake in hamsters in both photoperiods.

Animals↗

Hypoglycemia and torpor in Siberian hamsters.

We tested whether reduced blood glucose concentrations are necessary and sufficient for initiation of torpor in Siberian hamsters. During spontaneous torpor bouts, body temperature (Tb) decreases from the euthermic value of 37 to <31 degrees C. Among hamsters that displayed torpor during maintenance in a short-day length (10 h light/day) at an air temperature of 15 degrees C, blood glucose concentrations decreased significantly by 28% as Tb fell from 37 to <31 degrees C and increased during rewarming so that by the time Tb first was >36 degrees C, glucose concentrations had returned to the value preceding torpor. Hamsters did not display torpor when maintained in a long-day length (16 h light/day) and injected with a range of insulin doses (1-50 U/kg body mass), some of which resulted in sustained, pronounced hypoglycemia. We conclude that changes in blood glucose concentrations may be a consequence rather than a cause of the torpid state and question whether induction of torpor by 2-deoxy-D-glucose is due to its general glucoprivic actions.

Animals↗