Temporal Synergism of Corticosterone and Prolactin in the Syrian Hamster,Mesocricetus auratus

To augment the limited work reported in the literature regarding testing of the hormonal temporal synergism hypothesis in Syrian hamsters (Joseph MM, Meier AH. Proc Soc Exp Biol Med. 1974;146:1150-5), a large experiment with female hamsters was conducted. Forty-eight received corticosterone at 18:00 h on January 21, 23, 25, 27, and 29 and ovine prolactin at one of six times of day beginning January 22 for 8 days; 36 received saline (at 18:00) and prolactin at one of the six times of day for 8 days; 35 received only prolactin at one of the six times of day for 8 days; and 16 received no injections. Twelve hamsters receiving corticosterone and prolactin and eight uninjected hamsters were on running wheels. The corticosterone and prolactin group not on wheels had a body weight gain and no circadian rhythm of weight gain, but did have circadian rhythms of response in organ weight, per 100 g of body weight, and in weights of fat pads and uteri. The corticosterone and prolactin group with access to running wheels gained in body weight and had larger ovaries and smaller fat pads. Hamsters receiving saline and prolactin had a body weight gain, but had no circadian rhythms of response in organ weights. The hamsters receiving only prolactin gained in body weight but had no rhythms of response, except for unexpected circadian rhythms in body weight gain and weights of fat pads. The uninjected hamsters had a modest weight gain. Most or all hamsters with access to running wheels freeran, and the corticosterone injections did not appear to synchronize the locomotor activity rhythms. In conclusion, corticosterone does interact with the injection time effect of prolactin on weights of fat pads, paired ovaries, and uteri. The mechanism of that effect, in terms of circadian rhythm theory, is unclear.     

Circadian Neuroendocrine Role in Age-Related Changes in Body Fat Stores and Insulin Sensitivity of the Male Sprague-Dawley Rat

A role for circadian neuroendocrine rhythms in the age-related development of obesity and insulin resistance was investigated in the male Sprague-Dawley rat. The phases and amplitudes of the plasma rhythms of several metabolic hormones (i.e. corticosterone, prolactin, insulin, and triiodothyronine) differed in lean, insulin-sensitive (3-week-old rats). insulin-resistant (8-week-old rats) and obese, insulin-resistant (44-week-old rats) animals. Simulation of the daily rhythms of endogenous corticosterone and prolactin by daily injections of the hormones at times corresponding to the peak levels found in 3-week-old rats reversed age-related increases in insulin resistance and body fat in older (5-6-month-old) rats. Ten such daily injections of corticosterone and prolactin in 12-14-week-old rats produced long-term reductions in body fat stores (30%). plasma insulin concentration (40%'). and insulin resistance (60%) (determined by a glucose tolerance test) measured 11-14 weeks after the treatment. Alterations in circadian neuroendocrine rhythms may account for age-related changes in carbohydrate and lipid metabolism in the male Sprague-Dawley rat, and resetting of these rhythms by appropriately timed daily injections of corticosterone and prolactin may help maintain metabolism characteristic of younger animals.     

Circadian Neuroendocrine Role in Age-Related Changes in Body Fat Stores and Insulin Sensitivity of the Male Sprague-Dawley Rat

A role for circadian neuroendocrine rhythms in the age-related development of obesity and insulin resistance was investigated in the male Sprague-Dawley rat. The phases and amplitudes of the plasma rhythms of several metabolic hormones (i.e. corticosterone, prolactin, insulin, and triiodothyronine) differed in lean, insulin-sensitive (3-week-old rats). insulin-resistant (8-week-old rats) and obese, insulin-resistant (44-week-old rats) animals. Simulation of the daily rhythms of endogenous corticosterone and prolactin by daily injections of the hormones at times corresponding to the peak levels found in 3-week-old rats reversed age-related increases in insulin resistance and body fat in older (5-6-month-old) rats. Ten such daily injections of corticosterone and prolactin in 12-14-week-old rats produced long-term reductions in body fat stores (30%). plasma insulin concentration (40%″). and insulin resistance (60%) (determined by a glucose tolerance test) measured 11-14 weeks after the treatment. Alterations in circadian neuroendocrine rhythms may account for age-related changes in carbohydrate and lipid metabolism in the male Sprague-Dawley rat, and resetting of these rhythms by appropriately timed daily injections of corticosterone and prolactin may help maintain metabolism characteristic of younger animals.     

Effect of mammalian growth hormone and prolactin on the growth of hypophysectomized chickens

Body weight gain and shank-toe growth during a 26-day treatment period following hypophysectomy were 55 and 46%, respectively, of control values, but the body weight gain was unaffected and bone growth only slightly reduced when the hypophysectomized chickens were fed a low dose of corticosterone (5 ppm). Bovine growth hormone (0.5 mg GH/kg body wt/day for 18 days) enhanced body weight gain and shank-toe length increase (an estimate of bone growth) by 46 and 33%, respectively, compared to the growth of hypophysectomized chickens receiving only corticosterone. These same endpoints were increased approximately 24% after ovine growth hormone treatment in hypophysectomized chickens not receiving corticosterone. Body weight gain during 18 days of treatment with bovine prolactin (0.5 mg PRL/kg/day) was 27% greater than the value for corticosterone-treated hypophysectomized chickens, but bone growth was unaffected. The mammalian GH preparations increased heart weight of the hypophysectomized chickens (25-29%), but pectoralis muscle weight was unaffected. GH treatment enhanced thymal weights by 71% in corticosterone-treated hypophysectomized chickens, and by 93% in hypophysectomized animals not receiving corticosterone. GH had no significant effect on bursal weights, and PRL had no effect on either of these lymphoid organ weights in corticosterone-treated hypophysectomized chickens. GH increased liver and adipose tissue weights considerably more than the large increases that followed treatment of hypophysectomized chickens with corticosterone alone (69 and 126% greater, respectively), but had no effect on these endpoints in hypophysectomized chickens not receiving corticosterone. PRL also greatly increased liver and adipose tissue weights in corticosterone-treated hypophysectomized chickens (79 and 75%, respectively). These results provide evidence that mammalian GH enhances body weight gain, bone growth, and the growth of several organs in the hypophysectomized chicken. Mammalian PRL increased body weight gain, liver weight, and adipose tissue weight in corticosterone-treated hypophysectomized chickens, but did not influence bone growth or the weights of the heart, pectoralis, thymi, or bursa.     

Daily novel wheel running reorganizes and splits hamster circadian activity rhythms.

The phenomenon of splitting of locomotor activity rhythms in constant light has implied that the mammalian circadian pacemaker is composed of multiple interacting circadian oscillators. Exposure of male Syrian hamsters to novel running wheels also induces splitting in some reports, although novel wheel running (NWR) is better known for its effects on altering circadian phase and the length of the free-running period. In three experiments, the authors confirm and extend earlier reports of split rhythms induced by NWR. Male Syrian hamsters, entrained to LD 14:10, were transferred for 6 to 11 consecutive days to darkened novel Wahmann wheels at ZT 4 and were returned to their home cages at ZT 9. All hamsters ran robustly in the novel wheels. NWR caused a marked reorganization of home cage wheel-running behavior: Activity onsets delayed progressively with each additional day of NWR. After 11 days, activity onset in the nighttime scotophase was delayed by 7 h and disappeared completely in 2 hamsters (Experiment 1). After 6 to 7 days of NWR (Experiment 2), activity onset delayed by 5 h. Transfer of hamsters to constant darkness (DD) after 7 days of NWR revealed clearly split activity rhythms: The delayed nighttime activity bout was clearly identifiable and characterized by a short duration. A second bout associated with the former time of NWR was equally distinct and exhibited a similarly short duration. These components rejoined after 3 to 5 days in DD accomplished via delays and advances of the nighttime and afternoon components, respectively. The final experiment established that rejoining of activity components could be prevented by perpetuating the light-dark:light-dark cycle used to induce split rhythms. The data suggest that NWR causes selective phase shifting of some circadian oscillators and that component oscillators interact strongly in constant darkness.     

Intensive voluntary wheel running may restore circadian activity rhythms and improves the impaired cognitive performance of arrhythmic Djungarian hamsters

Circadian rhythms are highly important not only for the synchronization of animals and humans with their periodic environment but also for their fitness. Accordingly, the disruption of the circadian system may have adverse consequences. A certain number of animals in our breeding stock of Djungarian hamsters are episodically active throughout the day. Also body temperature and melatonin lack 24-h rhythms. Obviously in these animals, the suprachiasmatic nuclei (SCN) as the central pacemaker do not generate a circadian signal. Moreover, these so-called arrhythmic (AR) hamsters have cognitive deficits. Since motor activity is believed to stabilize circadian rhythms, we investigated the effect of voluntary wheel running. Hamsters were bred and kept under standardized housing conditions with food and water ad libitum and a 14 L/10 D lighting regimen. AR animals were selected according to their activity pattern obtained by means of passive infrared motion detectors. In a first step, the daily activity behavior was investigated for 3 weeks each without and with running wheels. To estimate putative photic masking effects, hamsters were exposed to light (LPs) and DPs and also released into constant darkness for a minimum of 3 weeks. A novel object recognition (NOR) test was performed to evaluate cognitive abilities both before and after 3 weeks of wheel availability. The activity patterns of hamsters with low wheel activity were still AR. With more intense running, daily patterns with higher values in the dark time were obtained. Obviously, this was due to masking as LPs did suppress and DPs induced motor activity. When transferred to constant darkness, in some animals the daily rhythm disappeared. In other hamsters, namely those which used the wheels most actively, the rhythm was preserved and free-ran, what can be taken as indication of a reconstitution of circadian rhythmicity. Also, animals showing a 24-h activity pattern after 3 weeks of extensive wheel running were able to recognize the novel object in the NOR test but not so before. The results show that voluntary exercise may reestablish circadian rhythmicity and improve cognitive performance.     

A Role for Testosterone in the Maintenance of Seasonally Appropriate Body Mass but not in Lipectomy-Induced Body Fat Compensation in Siberian Hamsters

The purpose of this study was to test whether serum testosterone (T) concentrations characteristic of reproductively active, long-day-housed Siberian hamsters are necessary for compensatory increases in nonexcised fat pads following removal of epididy-mal white adipose tissue (EWAT) and/or for the maintenance of seasonally appropriate body weights in these hamsters. Long-day-housed hamsters were castrated or left intact, sham or EWAT lipectomized, and given T or cholesterol (C) implants. All groups had ad libitum food access except for two castrated T-treated groups that were pair-fed to their C-treat-ed counterparts to control for effects of T on food intake. C-treated castrates had decreased body weights compared with all other groups, suggesting a role of T in the maintenance of seasonally appropriate body mass. Since the T-treated hamsters pair-fed to these T-deficient animals exhibited seasonally appropriate body weights and fat pad masses, T does not appear to affect these parameters through the modulation of food intake. All fat pads of C-treated animals were smaller than those of ad libitum- or pair-fed, T-treated castrates; however, EWAT was the only fat pad that was smaller in the C-treated sham-lipectomized group than in gonad-intact sham-lipectomized hamsters. This result may indicate an enhanced sensitivity of EWAT to T. The effects of T on fat pad mass were not associated with proportionate changes in lipoprotein lipase activity, suggesting that the major effect of T on fat accumulation occurs through other mechanisms in this species. C-treated lipectomized hamsters compensated for the body fat deficit 8 weeks after lipectomy via statistically nonsignificant increases in retroperitoneal and inguinal WAT mass. This finding suggests that, whereas T is necessary for maintenance of seasonally-appropriate body weight, it is not necessary for fat pad compensation after EWAT lipectomy.     

Evidence for independence of circadian characters and extent of photoresponsiveness in the Djungarian hamster, Phodopus sungorus.

Djungarian hamsters (Phodopus sungorus) exposed to a short-day photoperiod generally respond with a syndrome of physiological and behavioral changes, such as body weight loss and molt to a white pelage. The extent of the short-day-induced responses differs among individuals. Furthermore, some hamsters show no photoresponse. In this study, we sought to determine whether variation in the photoresponse would be associated with circadian function: whether phase angle or free-running period (tau) would differ between responsive and nonresponsive hamsters; and whether changes in these circadian characters would correlate with the extent of weight loss and molt (and the timing of molt onset) in photoresponsive hamsters. Adult hamsters were kept in a short-day photoperiod (9 hr light, 15 hr dark) for 14 weeks, during which time body weight and molt were measured biweekly. Hamsters were then transferred to cages equipped with running wheels; we measured the phase angle of activity onset under a short-day photoperiod and tau in constant dark. Hamsters exhibiting a short-day-induced molt had a significantly shorter tau and a less negative phase angle than nonmolting animals. Hamsters that exhibited weight loss also had a significantly less negative phase angle, but no difference in tau. No significant Pearson's or Spearman's correlation coefficients were found between extent (or timing) of the photoresponse and the circadian characters in responsive hamsters. Although these results indicate that threshold for photoresponsiveness is related to circadian function, the extent (and timing) of the photoresponse may not be.     

Leptin levels and body composition of mice selectively bred for high voluntary locomotor activity

Selective breeding produced four replicate lines of high-runner (HR) mice that run on wheels for approximately 2.7 times more revolutions per day than four unselected control lines. Previous studies found that HR mice of both sexes have lower body fat (isotope dilution at 15 wk of age) and that males (females not studied) have smaller retroperitoneal fat pads (17 wk). HR mice also exhibit elevated plasma corticosterone and insulin-stimulated glucose uptake by some hindlimb muscles but apparently do not differ in circulating insulin or glucose levels (males at 18 wk). Given their lower body fat and higher activity levels, we hypothesized that HR mice would have lower circulating leptin levels than controls. Female mice were given wheel access for 6 d at 7 wk of age, as part of the routine wheel testing for the selective breeding protocol, and then were killed after one additional week without wheels to reduce possible acute effects of activity on leptin. As hypothesized, serum leptin levels were significantly lower in HR mice. ANCOVA indicated that leptin was strongly positively correlated with both total body fat (measured by ether extraction) and body mass change from weaning, but HR mice still had significantly lower adjusted leptin levels (ANCOVA). Within HR lines but not within control lines, individual variation in leptin levels was negatively correlated with amount or speed of wheel running measured a week before being killed. Growth from weaning to euthanasia and body dry mass were lower in HR mice than in controls, but absolute dry masses of the ventricles, liver, gut, and uterus plus ovaries did not significantly differ, nor did percentage of the total dry mass as fat. HR mice offer a novel model for studying the causes and consequences of physiologically relevant variations in serum leptin.     

Circadian clock speed increases during aging in the male Syrian hamster: A large-scale study

There are conflicting reports in the literature as to whether or not the circadian period in Syrian hamsters shortens with age, and those studies were conducted with small sample sizes. This report mines data from a large number of experiments resulting in more than 1000 measurements of circadian period in hamsters during aging up to 6 months, and this was correlated with both age and weight. Circadian period was calculated while hamsters were in running wheels in constant darkness. There is a weak correlation between hamster weight and circadian period, and there is significant shortening of circadian period during aging.     

Effects of wheel running on photoperiodic responses of Djungarian hamsters (Phodopus sungorus)

Djungarian hamsters (Phodopus sungorus) were exposed to artificial short days either with access to a running wheel (RW) or without. Within 6 weeks RW hamsters considerably increased their body mass, whereas controls showed the typical body mass reduction. Estimation of paired testis weights indicated a decelerated testis regression in RW hamsters. Subsequent locking of RWs for 9 weeks led to a decline in body mass of RW animals in parallel to controls. Daily torpor was almost completely missing in hamsters with initially unlocked wheels. During the final phase when RWs were again unlocked (3 weeks), body mass of exercising hamsters increased again, while controls reached the nadir in body mass. In comparison to equiponderate long-day (LD) controls the relative liver weight of RW hamsters was significantly increased unlike the relative heart weight. However, the latter tended to be higher than in sedentary LD hamsters. A growth-stimulating effect of wheel running was proven by elongated femora in exercising short-day (SD) hamsters compared to SD controls and suggested by exercise-induced elevation of body mass in a further experiment under continuous LD conditions, indicating a growth-promoting effect of wheel running independent from the photoperiod.     

Effects of food deprivation on locomotor activity, plasma glucose, and circadian clock resetting in Syrian hamsters

Circadian rhythms in Syrian hamsters can be phase advanced by activity or arousal stimulated during the daily rest phase ("subjective day"). A widely used method for stimulating activity is confinement to a novel wheel. Some hamsters decline to run, and some procedures may reduce the probability of running. The authors evaluated food deprivation (FD) as a method to promote running. Given evidence that perturbations of cell metabolism or glucose availability may affect circadian clock function in some tissues or species, they also assessed the effects of FD on free-running circadian phase, resetting responses to photic and nonphotic stimuli and plasma glucose. In constant light, a 27-h fast significantly increased running in a novel wheel and marginally increased the average size of resulting phase shifts. FD, without novel wheel confinement, was associated with some very large phase shifts or disruption of rhythmicity in hamsters that spontaneously ran in their home wheels during the subjective day. Hamsters that ran only during the usual active phase (subjective night) or that were prevented from running did not exhibit phase shifts, despite refeeding in the mid-subjective day. Using an Aschoff Type II design for measuring shifts, a 27-h fast significantly increased the number of hamsters that ran continuously when confined to a novel wheel but did not affect the dose-response relation between the amount of running and the size of the resulting shift. A day of fasting also did not affect the size of phase delay or advance shifts to 30-min light pulses in the subjective night. Plasma glucose was markedly reduced by wheel running in combination with fasting but was increased by running in nonfasted hamsters. These results establish FD as a useful tool for stimulating activity in home cage or novel wheels and indicate that in Syrian hamsters, significant alterations in glucose availability, associated with running, fasting, and refeeding, have surprisingly little effect on circadian pacemaker function.     

ACTIVITY RHYTHMS OF WILD AND LABORATORY GOLDEN HAMSTERS (MESOCRICETUS AURATUS) UNDER ENTRAINED AND FREE-RUNNING CONDITIONS

The golden hamster (Mesocricetus auratus) is one of the most frequently used laboratory animals, particularly in chronobiological studies. One reason is its very robust and predictable rhythms, although the question arises whether this is an inbreeding effect or rather is typical for the species. We compared the daily (circadian) activity rhythms of wild and laboratory golden hamsters. The laboratory hamsters were derived from our own outbred stock (Zoh:GOHA). The wild hamsters included animals captured in Syria and their descendants (F1). Experiments were performed under entrained (light: dark [LD] 14h:10h) and under free-running (constant darkness, DD) conditions. Locomotor activity was recorded using passive infrared detectors. Under entrained conditions, the animals had access to a running wheel for a certain time to induce additional activity. After 3 weeks in constant darkness, a light pulse (15 min, 100 lux) was applied at circadian time 14 (CT14). Both laboratory and wild hamsters showed well-pronounced and very similar activity rhythms. Under entrained conditions, all hamsters manifested about 80% of their total 24h activity during the dark portion of the LD cycle. The robustness of the daily rhythms was also similar. However, interindividual variability was higher in wild hamsters for both measures. All animals used the running wheels almost exclusively during the dark portion of the LD cycle, although the wild hamsters were three times more active. The period length, measured in constant darkness, was significantly shorter in wild (23.93h ± 0.10h) than in laboratory hamsters (24.06 ± 0.07h). The light-induced phase changes were not different (about 1.5h). In summary, these results indicate that the laboratory hamster is not much different from the wild type. (Chronobiology International, 18(6), 921-932, 2001)     

Circadian rhythms of self-selected lighting in golden hamsters: relation to gonadal condition

Golden hamster (20 males, 8 females) were maintained in isolation boxes for 4-7 weeks. The animals had access to wheels and selected their own lighting by pressing one bar to turn light-on and another bar to turn the light-off. All hamsters maintained circadian rhythms of wheel-running activity. Seventeen of 28 hamsters selected lighting with a circadian periodicty. For 9 hamsters, there was a significant positive correlation between wheel-running activity and self-selected darkness, while this correlation was significantly negative for 10 hamsters. Four hamsters had regressed testes at the end of the experiment. These 4 had significant positive correlations between activity and self-selected darkness, while none of the hamsters with significant negative correlations between activity and self-selected darkness had regressed testes. Light in phase with activity seems to be more important to the prevention of testicular regression than is the total daily amount of light.     

The thalamic intergeniculate leaflet mediates locomotor activity-induced reversal of phenotype in photoperiod nonresponsive Siberian hamsters

The role of the intergeniculate leaflet of the thalamus (IGL) in photoperiod responsiveness was examined in a laboratory-selected line of photoperiod nonresponsive (NR) Siberian hamsters. NR hamsters fail to exhibit typical winter-type responses (i.e., gonadal regression and development of winter-type pelage) when exposed to short day lengths (e.g., 10 h of light/day). Earlier studies revealed that NR hamsters will exhibit winter-type responses when exposed to short photoperiod if they are given free access to a running wheel. The present study tested the hypothesis that this locomotor activity-induced reversal of phenotype is dependent on the IGL. Male NR hamsters underwent destruction of the IGL prior to being housed in short day lengths in cages equipped with running wheels. Activity rhythms were monitored for 8 weeks, after which time pelage response and paired testes weights were obtained. In contrast to sham-operated NR animals given access to running wheels, IGL-ablated animals showed no increase in the duration of nocturnal running wheel activity and became active later in the night than sham-lesioned animals. Lesioned animals also failed to exhibit the typical short photoperiod-induced gonadal regression and pelage molt. The results implicate the IGL in the mechanism by which running wheel activity can influence photoperiodic responses.     

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.     

ACTIVITY RHYTHMS OF WILD AND LABORATORY GOLDEN HAMSTERS (MESOCRICETUS AURATUS) UNDER ENTRAINED AND FREE-RUNNING CONDITIONS

The golden hamster (Mesocricetus auratus) is one of the most frequently used laboratory animals, particularly in chronobiological studies. One reason is its very robust and predictable rhythms, although the question arises whether this is an inbreeding effect or rather is typical for the species. We compared the daily (circadian) activity rhythms of wild and laboratory golden hamsters. The laboratory hamsters were derived from our own outbred stock (Zoh:GOHA). The wild hamsters included animals captured in Syria and their descendants (F1). Experiments were performed under entrained (light: dark [LD] 14h:10h) and under free-running (constant darkness, DD) conditions. Locomotor activity was recorded using passive infrared detectors. Under entrained conditions, the animals had access to a running wheel for a certain time to induce additional activity. After 3 weeks in constant darkness, a light pulse (15 min, 100 lux) was applied at circadian time 14 (CT14). Both laboratory and wild hamsters showed well-pronounced and very similar activity rhythms. Under entrained conditions, all hamsters manifested about 80% of their total 24h activity during the dark portion of the LD cycle. The robustness of the daily rhythms was also similar. However, interindividual variability was higher in wild hamsters for both measures. All animals used the running wheels almost exclusively during the dark portion of the LD cycle, although the wild hamsters were three times more active. The period length, measured in constant darkness, was significantly shorter in wild (23.93h ± 0.10h) than in laboratory hamsters (24.06 ± 0.07h). The light-induced phase changes were not different (about 1.5h). In summary, these results indicate that the laboratory hamster is not much different from the wild type. (Chronobiology International, 18(6), 921–932, 2001)     

Gonadal regression despite light pulses coincident with locomotor activity in the Syrian hamster

Feedback lighting (LDFB), which illuminates an animal cage in response to active wheel running, exposes only the photosensitive portion of the phase-response curve to light. In the hamster, the photoinducible zone of the circadian rhythm of photoperiodic photosensitivity occurs during the interval of active wheel running. Since LDFB exposes the photoinducible zone almost as much as constant light (LL), we predicted that LDFB would maintain gonadal function just as LL does. Surprisingly, 10 male hamsters exposed to 1-sec pulses of LDFB for 8 wk had regressed testes similar to those of hamsters in continuous darkness (DD) and significantly smaller than hamsters exposed to LL (P less than 0.01). Two of 5 male hamsters exposed to 2-min pulses of LDFB underwent complete testicular regression and two had partially regressed testes. All females exposed to LDFB or to DD ceased showing cyclic signs of ovulation within 20 days, whereas most hamsters exposed to LL continued to show signs of cyclic ovulation. Six of the 8 hamsters exposed to LL had ova in their oviducts at autopsy, and also had significantly larger uteri (P less than 0.01) than hamsters exposed to DD or LDFB. None of the latter two groups (n = 6 and 9, respectively) had oviductal ova at autopsy. These results demonstrate that considerable exposure of the photoinducible zone to light does not necessarily maintain gonadal function. Light delivered to the photoinducible zone by LDFB may disrupt the normal alignment (internal coincidence) of circadian rhythms, thereby causing gonadal regression. Gonadal induction can occur when the photoinducible zone is exposed to light; however, it may not be the light itself, but rather the action of the light to alter the phase relationships of several oscillators, that causes induction and maintenance of the gonads.     

Effect of ovarian transplantation to the uterus ("Estes operation") on reproduction in the rabbit

The effectiveness of the "Estes operation," which was developed to correct fertility problems in humans suffering from tubal incompetence, was studied using rabbits. The ovaries of mature does were surgically transplanted into their uteri and the effects of this altered state on reproduction, host tissue and graft tissue were appraised. Animals with transplanted ovaries showed normal breeding behavior, but the only pregnancies resulted when does that had received heterotransplanted ovaries also retained their own ovaries in situ . Young produced in those pregnancies were shown to have originated from ova ovulated from the host's normal ovaries. Transplanted ovaries disappeared from the uterus, either by resorption or expulsion, within eight weeks if they were separated from their pedicles but were retained if left attached to their pedicles. Presumably the difference reflects the state of vascularization. Scar tissue developed at the junction of ovary and uterus, and the endometrial epithelium became continuous with the germinal epithelium of the ovary. The uteri receiving pedicled ovaries retained their normal size. Those of ovariectomized does were about half the weight of normal uteri and those of ovariectomized does receiving unpedicled ovaries atrophied to a size about half those of the ovariectomized does. When intact does received heterotransplanted ovaries in their uteri, those uteri hypertrophied to approximately twice the size of normal uteri. The effects of transplanting ovaries to the uterine lumen, as reported here, could explain the poor pregnancy success rate in humans and the complete failure to achieve pregnancies in any other mammalian species by use of the "Estes operation."     

Three weeks of early-onset exercise prolongs obesity resistance in DIO rats after exercise cessation

We assessed the effect of early-onset exercise as a means of preventing childhood obesity using juvenile male rats selectively bred to develop diet-induced obesity (DIO) or to be diet resistant (DR) when fed a 31% fat high-energy diet. Voluntary wheel running begun at 36 days of age selectively reduced adiposity in DIO vs. DR rats. Other 4-wk-old DIO rats fed a high-energy diet and exercised (Ex) for 13 wk increased their core temperature, gained 22% less body weight, and had 39% lighter fat pads compared with sedentary (Sed) rats. When wheels were removed after 6 wk (6 wk Ex/7 wk Sed), rats gained less body weight over the next 7 wk than Sed rats and still had comparable adipose pad weights to 13-wk-exercised rats. In fact, only 3 wk of exercise sufficed to prevent obesity for 10 wk after wheel removal. Terminally, the 6-wk-Ex/7-wk-Sed rats had a 55% increase in arcuate nucleus proopiomelanocortin mRNA expression vs. Sed rats, suggesting that this contributed to their sustained obesity resistance. Finally, when Sed rats were calorically restricted for 6 wk to weight match them to Ex rats (6 wk Rstr/7 wk Al), they increased their intake and body weight when fed ad libitum and, after 7 wk more, had higher leptin levels and adiposity than Sed rats. Thus, early-onset exercise may favorably alter, while early caloric restriction may unfavorably influence, the development of the hypothalamic pathways controlling energy homeostasis during brain development.