Glucoprivic regulation of estrous cycles in the rat

Previous research has shown that glucoprivation induced by chronic 2-deoxy-D-glucose (2DG) treatment extends estrous cycle length and disrupts reproductive behaviors in female hamsters, similar to food deprivation. Such treatment also suppresses food intake, which is reversed in male rats by reducing brain histamine levels prior to 2DG treatment. We, therefore, determined if 2DG extends estrous cycles in the female rat and if this is due to elevated brain histamine levels. We measured estrous cycle length during 2DG-induced glucoprivation, in the presence and absence of alpha-fluoromethylhistidine (FMH), a treatment that reduces brain histamine levels. Adult female rats were treated for 72 h with either saline (n = 8), 2DG (200 mg/kg S.C. every 6 h; n = 9), or FMH (100 mg/kg i.p. daily) + 2DG (200 mg/kg; n = 7). An additional group was treated with FMH (100 mg/kg i.p.; n = 5) alone. To determine if 2DG extends estrous cycles due to glucoprivation or to decreased caloric intake, a group of rats (n = 7) received a reduced diet equal to the mean daily food intake of rats receiving 2DG alone. 2DG induced more long estrous cycles compared to rats receiving saline, FMH + 2DG, or FMH alone. In rats treated with FMH + 2DG, the percentage of 4-5-day cycles was similar to that of saline-treated rats, and a high percentage of 4-5-day cycles was also observed in rats receiving a reduced diet. These data suggest that 2DG does not suppress estrous cycles through a decrease in total calorie intake, but rather by inducing glucoprivation. In addition, during 2DG-induced glucoprivation, elevated brain histamine levels contribute to the mechanism that suppresses reproductive function.     

Disruption of estrous cycles in exercise-trained rats

The female Sprague-Dawley rat was evaluated as an animal model for the menstrual irregularities that are common in women athletes. Daily vaginal smears revealed that estrous cycles were markedly disrupted in rats during a 10-week exercise training program, while cycles remained normal in sedentary rats. Compared to 9 sedentary rats, the 10 exercise-trained rats had longer mean cycle lengths and fewer estrus smears. Six of the exercise-trained rats, but none of the sedentary rats, had an "anestrus period" with more than twice the normal interval between estrus smears; one exercise-trained rat became essentially acyclic. Weight gain during the 10-week training program was lower in exercise-trained rats than in sedentary rats. Colonic temperatures, monitored at rest and during 30 min of exercise, were slightly lower in exercise-trained rats with irregular estrous cycles than in exercise-trained rats with regular cycles, indicating that unusually elevated body temperatures during exercise are not responsible for exercise-related reproductive acyclicity. It is concluded that the female Sprague-Dawley rat may be a useful animal model for the study of menstrual irregularities associated with exercise training.     

A comparative study of adrenal progesterone secretion during the estrous cycles of hamsters and rats

Adrenal secretory rates and peripheral plasma levels of progesterone (PROG) were determined during the estrous cycles of hamsters and 4-day cyclic rats. In both species, the PROG concentrations in peripheral plasma were never more than 6% of those observed in adrenal venous plasma. In hamsters, adrenal PROG secretory rates varied from 3.8 ± 0.8 ng/min at 0800 hr on proestrus (P) to 8.5 ± 1 ng/min at 2000 hr on estrus (E). The rates noted on P were among the lowest observed and were similar to those noted at 0800 hr the following morning. In rats, adrenal PROG secretory rates varied from 57 ± 9 ng/min at 0800 hr on E to 130 ± 18 ng/min at 2000 hr on P. A significant decline occurred between 2000 hr on P and 0800 hr the following morning. Rats secreted 3 to 8 times more PROG than did hamsters when the secretory rates are expressed as ng/min/100 mg adrenal. In hamsters, the data suggest a relative lack of influence of female reproductive hormones on adrenal PROG secretion and in turn the latter may not be involved in reproductive hormonal changes leading to ovulation. In rats, the increased adrenal PROG secretion noted on P may be due to the influence of reproductive hormones on adrenocortical function. This elevated rate may in turn influence the hypothalamo-hypophyseal-ovarian axis.     

Restoration of fertility in light-deprived female hamsters by chronic melatonin treatment

Summary Blinding young adult female hamsters was followed by functional involution of the ovaries and uteri and by the cessation of cyclic vaginal phenomena. Light deprivation was also accompanied by elevated plasma and pituitary levels of luteinizing hormone and depressed levels of prolactin in both the blood and the pituitary gland. Only one of 15 blinded hamsters became pregnant when they were exposed to fertile males for 30 days. Both pinealectomy or chronic melatonin treatment (1 mg melatonin implanted subcutaneously per week in beeswax) prevented the changes in the reproductive organs and in pituitary hormone levels attendant on light-deprivation. Both treatment also returned vaginal cycles to normal and restored plasma prolactin titers. Unlike hamsters that were blinded only, light deprived hamsters that were either pinealectomized or melatonin treated were capable of reproducing when they were caged with fertile males. The reproductive capability (i.e., percent of animals that become pregnant and the sizes of their litters) of these animals was equivalent to that of the untreated control hamsters. This is the first report that chronic melatonin treatment restores fertility in blinded female hamsters.Supported by Grant GB-43233X from the National Science Foundation     

The involvement of suprachiasmatic nuclei in the regulation of estrous cycles in rodents

Originally suprachiasmatic nuclei (SCN) were considered the main center of signals regulating the cyclic function of female reproduction, especially the gating of the LH surge. It was confirmed in the rat but not in the hamster. Some recent data show that multiple and complex interactions and processes underlie the occurrence of this very important and crucial event in female reproduction: the LH surge. Thanks to such multiway and multifactor control, the LH surge and the resulting ovulation occur regularly when "the time window" opens. Involvement of the SCN and other nuclei of the respective area in the regulation of rhythmic reproductive phenomena in female rats and hamsters is discussed.     

Induction of P-450 isoenzyme activities in Syrian golden hamster liver compared to rat liver as probed by the rate of 7-alkoxyresorufin-O-dealkylation

The activities of 7-ethoxyresorufin-O-deethylase (EROD), 7-pentoxyresorufin-O-deethylase (PROD), 7-ethoxycoumarin-O-deethylase (ECOD) and aromatic hydrocarbon hydroxylase (AHH) were measured in hepatic microsomes from male and female Wistar rats and Syrian golden hamsters in order to probe the basal activity and the inducibility by phenobarbital (PB) and 3-methylcholanthrene (MC) of different P-450 isoenzymes. The basal activities of EROD and ECOD, but not PROD and AHH, were higher in male hamsters than in male rats. No sex-related difference in enzyme activities was observed with hamsters, whereas male rats had a higher ECOD and AHH activity than female rats. Induction by PB led to a 450-fold and 250-fold increase in PROD activity in male and female rat liver microsomes, respectively, while MC had a more pronounced inductive effect on EROD activity in this species. In hamsters, EROD activity was induced by MC but not by PB. Unexpectedly PROD activity in male and female hamster liver microsomes was only moderately induced by PB, the extent being lower than on induction by MC. Therefore, the activity of PROD, which is useful as a specific enzymatic assay for P-450 IIB in the rat liver, cannot be used to probe PB-like inducers in the hamster liver.     

Transmission modes of Pneumocystis carinii among rats observed by karyotype analysis.

To observe the transmission patterns of karyotype of Pneumocystis carinii (Pc) by rat colonies, three strains of rats, Sprague-Dawley(SD), Wistar(W) and Fisher(F) from various animal vendors, were suppressed of their immunity by injection of methyl prednisolone. They were kept for 5 to 13 weeks in 3 different animal rooms, A, B, and C. The purified organisms were prepared in low melting point agarose gel by embedded lysis method for pulsed field gel electrophoresis. Field inversion gel electrophoresis showed 2 patterns of the karyotype of Pc. The rooms A and C contained SD rats from the source P, and also the room A was used for F and W rats. However, Pc from all of the SD and F rats in the room A showed same karyotypes, the pattern I. The SD rats from different vendors, M and S, were reared in the room B, and shared the same Pc karyotypes, the pattern II. The rats of W strain were from the vendor M, and immune-suppressed in the animal room A. Five weeks after the experiment, the Pc showed the karyotype pattern II but the pattern became mixed with the type I after 7 to 8 weeks. The findings revealed that the animals born and reared in the same animal quarter harbored Pc with same karyotypes. If the animals were kept under immune-suppression in the same room with heavily infected hosts, they could be infected by Pc from their neighbors. The present experimental findings suggest that Pc is transmitted among rats through the air.     

Observation on the air-borne bacteria and ammonia (NS3) gas in laboratory animal facility with rotary heat exchanger]

The number of air-borne bacteria in air ducts and barrierred laboratory animal rooms with the so-called econovent rotary heat exchanger, were checked monthly during a year by the pin-hole sumpler method for air ducts and Koch method for animal rooms. Also, concentration of ammonia was checked with the same samples by gas impinger. No significantly difference in number of air-borne bacteria was seen between before and after passing the econovent. Those passing through HEPA filter was not detected. There were more air-borne bacteria in animal rooms, outside locker room and shower room than in the corridor, utensil storage, inside locker room and pass box. No ammonia were detected in the outdoor, but exhaust air duct after passing the econovent contained very small amount of ammonia. On the other hand, high concentration of ammonia were preserved in the supplying air duct, exhaust air duct and mice and rats rooms, about 86% of ammonia in exhaust air duct returned back into the supplying air duct. No influences on reproduction in mice and rats were recognized.     

Deceleration of age-associated changes in the preovulatory but not secondary follicle-stimulating hormone surge by progesterone

Recently, it has been reported that mating can delay the age-associated decline in reproductive function of female rats. Since circulating progesterone (P) levels are elevated for a 2- to 3-wk interval during pregnancy, the following study was conducted to determine whether intermittent elevation in P levels can alter the rate of reproductive aging in female rats. Beginning at 2 mo of age, 4-day-cycling, virgin rats were divided into two groups. In one group, 3 Silastic capsules containing crystalline P were inserted s.c. into each rat while rats in another group each received 1 empty capsule. After 2 wk, the capsules were removed for 2 wk. Thereafter, implantation and removal of capsules was repeated 5 additional times. Rats receiving P capsules became acyclic 3-4 days after exposure to P and resumed cyclicity 4-7 days after removal of P-capsules. One month after the last series of capsules was removed (rats approximately 8-mo-old), rats exhibiting consecutive 4-day cycles were inserted with indwelling atrial cannulae and bled at 4-h intervals from 1400 h on proestrus (Pr) to 1000 h on estrus (E). At 1600 h E, rats were killed and trunk blood was collected. For comparison, a group of 3-mo-old (young) rats was bled on Pr and E. In 8-mo-old rats that received empty capsules, 27% exhibited 4-day cycles compared to 66% of the young rats. However, in contrast to rats that received empty capsules, 63.1% of P-treated rats exhibited 4-day cycles. Surges of preovulatory luteinizing hormone (LH) and follicle-stimulating hormone (FSH) surges were attenuated in 8-mo-old rats given empty capsules compared to young rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Melatonin-pineal relationships in female golden hamsters.

Light deprivation by blinding in female hamsters was followed by a regression of the reproductive organs, an elevation of pituitary LH concentration and a depression of pituitary prolactin levels. Pinealectomy negated almost completely the effects of light deprivation on the neuroendocrine-reproductive axis. Weekly subcutaneous implants of a melatonin:beeswax pellet completely prevented the pineal gland from inhibiting reproductive physiology in blinded hamsters. The findings suggest that melatonin is not pineal antigonadotrophic factor in female golden hamsters. Melatonin implanted hamsters also had higher than normal levels of plasma prolactin.     

Inhibition of estrous cyclicity in golden hamsters by melatonin administration on the day of proestrus

Single injections of melatonin (25 micrograms) were administered to female hamsters, 15 minutes before lights-out (14L:10D), during either the early diestrous (day 1) or proestrous (day 4) phase of the estrous cycle. Hamsters which received melatonin only on the evening of proestrus became anovulatory by three weeks of treatment, while those that were injected with melatonin during diestrus, or administered oil on either day 1 or 4, continued to exhibit normal estrous cycles. These results indicate that quartan injections of melatonin can suppress reproductive function in female hamsters, and that the effectiveness of the injections may be dependent upon the stage of the estrous cycle at which they are administered.     

Isolation accelerates reproductive senescence and alters its predictors in female rats

The process of reproductive senescence in female rats (Rattus norvegicus, Sprague-Dawley strain) was altered by their social environment during adulthood. The incidence of constant estrus (CE), which marks the end of estrous cyclicity, was nearly twice as high in females living in isolation as it was in females living in groups. Isolated females also entered CE at three times the rate of group-housed females. In addition, the characteristics of a rat's estrous cycle when she was young predicted whether or not she would enter CE during reproductive senescence. However, the characteristics of the cycle that predicted if a rat would enter CE were different for isolated females than for females living in groups. In isolated rats, entry into CE was predicted by a pattern of regular cycles followed by irregular cycles, a lordosis reflex of consistently high intensity during irregular cycles, and an absence of spontaneous pseudopregnancies. Furthermore, a long duration of CE was predicted by early cessation of estrous cycles. In rats living in groups, increased estrogenization of the vaginal smears during irregular cycles was the only predictor of entry into CE. In both environments, the onset of an acyclic lordosis reflex predicted the timing of CE. The potential role of ovarian steroids as mediators of these effects is discussed.     

The effects of melatonin and hypothyroidism on estradiol and gonadotropin levels in female Syrian hamsters

Since melatonin injections administered near the end of the daily photoperiod influence both gonadal and thyroid hormones in the female hamster, the present study was designed to compare the effects of melatonin and hypothyroidism on the reproductive system and to determine whether thyroid status influenced the action of melatonin on the regulation of the hormones of reproduction. The effects of daily melatonin injections were determined in control hamsters, in hamsters rendered hypothyroid with thiourea, and in hypothyroid hamsters receiving thyroxin (T4) hormone replacement. As previously reported, melatonin injections disrupted estrous cyclicity, disrupted the normal pattern of gonadotropin secretion, and resulted in atrophy of the uterus and vagina. These changes coincided with depressed serum and pituitary prolactin (PRL), and depressed levels of estradiol. The effects of melatonin on uterus, vagina, ovary, and on gonadotropin levels were not prevented by T4 replacement, with the exception of a melatonin-induced increase in serum follicle-stimulating hormone (FSH). This suggested that the cessation of estrous cyclicity was not primarily a result of thyroid deficiency. Hypothyroidism, however, like melatonin, resulted in a reduced number of developing and mature follicles and corpora lutea in the ovaries, and in reduced uterine weight. It also produced follicular atresia, reduced the circulating levels of estradiol, and resulted in reduced incidence of estrus smears. T4 replacement, for 2 weeks, prevented the decline in mature follicles and corpora lutea, reduced the extent of follicular atresia, increased circulating levels of estradiol, and increased uterine weight. PRL and luteinizing hormone (LH) data also provided evidence for antagonistic effects of melatonin and T4 in female hamsters. These data raise the question whether melatonin-induced changes in circulating levels of T4 play a role in the seasonal cycles of reproductive competence in the female hamster.     

Influence of photoperiod and gonadal steroids on hibernation in the European hamster

Torpor was monitored daily in adult male and female European hamsters (Cricetus cricetus) induced to hibernate by exposure to a cold environment (6 degrees C). The effect of photoperiodic manipulations or administration of exogenous gonadal steroids was examined in gonadectomized or intact hamsters. 1. Gonadal regression occurred in all short day, but only in some long day, cold-exposed hamsters. Entry into hibernation was not observed until reproductive regression had occurred. Thus, gonadal atrophy appears to be a necessary precondition for hibernation. 2. Castrated hamsters in the short day cold condition showed a significantly greater incidence of torpor than those in the long day cold condition. Hence, photoperiod affected torpor independently of its effect on the gonadal cycle. 3. Testosterone, when administered via silastic capsules at near physiological levels, completely inhibited torpor in gonadectomized male and female hamsters hibernating in the short day cold condition. 4. In ovariectomized females, torpor was unaffected by progesterone treatment, but partially inhibited by estradiol. A greater inhibition of torpor was observed when estradiol-primed females were administered both estradiol and progesterone simultaneously. Thus, the effect of both hormones may be functionally comparable to that of the single testicular hormone. 5. Estradiol inhibited torpor to a greater extent in intact and ovariectomized female hamsters hibernating in long days than those in short days, suggesting an effect of photoperiod on responsiveness to estradiol. These results indicate an inverse relationship between the gonadal and hibernation cycles, and a probable role for gonadal steroids to influence the timing of the hibernation season. However, non-gonadal factors must also be involved in controlling hibernation, since photoperiod affected the incidence of torpor in gonadectomized animals and because hamsters were able to terminate hibernation in the absence of gonadal hormones.     

Male Syrian hamsters demonstrate a conditioned place preference for sexual behavior and female chemosensory stimuli

Sexual behavior is a natural reward for many rodent species, and it often includes chemosensory-directed components. Chemosensory stimuli themselves may also be rewarding. Conditioned place preference (CPP) is one paradigm frequently used to test the rewarding properties of a range of stimuli. Males and females of several rodent species show a CPP for sexual behavior; however, it is currently unknown whether sexual behavior can induce a CPP in male Syrian hamsters. As male Syrian hamsters are an animal model commonly used for investigation of the neurobiology of sexual behavior, understanding the rewarding components of sexual stimuli will better direct future research on brain regions and neurotransmitters involved in these behaviors. Experiment 1 tested the prediction that male hamsters show a CPP for sexual behavior. Female chemosensory stimuli are essential for the display of sexual behavior in male hamsters; however, the rewarding properties of female chemosensory stimuli contained in vaginal secretions (VS) are uncertain. Therefore, experiment 2 tested the prediction that male hamsters show a CPP for VS. This study is the first demonstration that both sexual behavior and VS induce a CPP in male hamsters. Thus, female chemosensory stimuli are a natural reward in a species that is dependent on these stimuli for reproductive fitness.     

Asynchrony in the estrous cycles of golden hamsters (Mesocricetus auratus)

The golden hamster has been described as exhibiting estrous cycle synchrony caused by social dominance. This has recently been reexamined by J. C. Schank (2000, Horm. Behav. 38, 94-101) with the aid of computer simulations. He concluded that there is no evidence for cycle synchrony among golden hamsters. In the present article we confirm this theoretical approach with the help of long-term experiments. Indeed, estrous cycle asynchrony was observed. Singly housed female golden hamsters in phase with their neighbors and in physical contact desynchronized their 4-day cycles after 2 or 3 weeks. Asynchrony was caused mainly by stochastic 5-day cycles. Statistical analysis was performed using a Monte-Carlo bootstrap approach. Based on the empirical data, an individual-based computer model was developed to simulate the dynamics of cycle desynchronization. Potential advantages were deduced for the population level. It emerged that estrous cycle asynchrony led to higher reproductive success for females where the probability of fertilization was low (e.g., after hibernation, poor habitat).     

The effect of cold stress on ganglioside fatty acid composition and ganglioside-bound sialic acid content of rat brain subcellular fractions

The effect of cold stress on the ganglioside fatty acid composition and sialic acid content of brain subcellular fractions and homogenate of rats was studied, the animals were kept in a cold room with 12h light-dark cycles at 3 and 10 degrees C for 2 weeks. (1) The rat brain homogenate, synaptosomes and myelin of rats exposed to 3 degrees C contained significantly higher amounts of ganglioside-bound sialic acid per mg of protein than these fractions of control rats kept at 23 degrees C; the differences were less pronounced in rats exposed to 10 degrees C. (2) A small, but significant, diminution of relative palmitic acid content and an increase of stearic acid content was found to take place in gangliosides from rat brain synaptosomes, synaptosomal plasma membranes and homogenate as a result of the exposure of animals to 3 degrees C and to a lesser extent to 10 degrees C. (3) The content of unsaturated fatty acids in gangliosides from brain subcellular fractions was approximately the same in cold exposed and control rats.     

Androgen and estradiol levels in plasma and amniotic fluid of late gestational male and female hamsters: uterine position effects

Using radioimmunoassay we have measured the plasma and amniotic fluid levels of androgen and estradiol in male and female hamster fetuses nearing parturition. On Days 14 and 15 of gestation (day of birth = Day 16), plasma levels of androgen are higher in males than females while estradiol levels are equal. Amniotic fluid levels of these hormones, while lower than plasma, reflect the difference in androgen and the similarity in estradiol between sexes. Uterine position analysis on Day 14 suggests that female siblings located caudally suppress amniotic fluid androgen and elevate estradiol levels of male siblings. Comparison of Day 18 gestation male and female rat amniotic fluid androgen to Day 14 hamsters reveals that male rats are bathed in high levels of androgen. Female rats have lower levels which are not different from those of male hamsters. Female hamsters are exposed to little androgen. Relevance to behavioral sexual differentiation and the display of adult behavior is discussed.     

Age at puberty and first litter size in early and late paired rats

The rate of sexual maturation among female Sprague-Dawley rats was measured in a variety of intraspecific social environments. It was found that females of this strain differ from at least one other strain of laboratory rat in that neither age at vaginal perforation nor age at first estrus was affected in Sprague-Dawley females by the presence or absence of male, regardless of his age or breeding history. Sizes of first litter among females who mated at their first estrus were compared with those among females who were first inseminated at older ages. On average, females bred at first estrus produced litters that contained more than 3 fewer pups than females mated at older ages. This observation suggests that female Sprague-Dawley rats do not attain full reproductive competence until sometime after the onset of puberty.     

Inapparent Streptococcus pneumoniae type 35 infections in commercial rats and mice

Streptococcus pneumoniae was isolated from specific-pathogen-free rodents in two rooms at a commercial breeding facility during vendor surveillance testing. In a survey of 274 animals from the two rooms over a period of 7 months, capsular serotype 35 S. pneumoniae was isolated from the upper respiratory tracts of 11% (9 of 82) of C57BL/6 mice in room A and 14% (10 of 72) of F344 rats in room B, but not from WKY rats, BALB/c mice or DBA/2 mice from room A. In both C57BL/6 mice and F344 rats, older rodents had higher colonization frequencies. Nasal lavage cultures gave the best results in identifying colonized rodents. No clinical illness or microscopic lesions were associated with pneumococcal colonization in rats or mice, and no other evidence of potential pathogen infection was found except for positive serologic tests for mouse rotavirus in mice. This is the first report of natural pneumococcal infection in mice, and the first report of type 35 S. pneumoniae infection in rodents. The findings support an earlier observation that pneumococcal infections in rat colonies tend to be monotypic and suggest that the same may be true in mice.