Effects of diet and exposure to hindlimb suspension on estrous cycling in Sprague-Dawley rats

Various factors can disrupt the female reproductive cycle resulting in subfertility. The primary objective of this study was to determine whether physiological changes associated with exposure to hypogravity disrupt reproductive cycles. The hindlimb suspension (HLS) model was used to simulate the major physiological effects of hypogravity in female Sprague-Dawley rats. Also, to determine whether diet may influence reproductive results, rats were fed purified American Institute of Nutrition (AIN)-93G or chow diet. Rats (n = 9-11/group) subjected to HLS had lengthened estrous cycles due to prolonged diestrus, indicating hypoestrogenism. Interestingly, HLS rats fed AIN-93G but not chow diet had significantly reduced time spent in estrus and decreased plasma estradiol. Attenuation of hypoestrogenism in the chow-fed rats suggested that diet provided an exogenous source of estrogen. The mechanism involved in the disruption of estrous cycling remains to be determined. HLS increased urinary corticosterone (CORT) levels during the initial 4 days of HLS, suggesting that physiological responses to acute stress may be a potential mechanism in the disruption of estrous cycles. Higher basal urinary CORT was observed in rats fed chow vs. AIN-93G diet. HLS resulted in increased urinary CORT. However, two-way ANOVA indicated a significant HLS effect (P < 0.001) but no effect of HLS x diet effect on urinary CORT levels, suggesting that estrogenic activity associated with the chow diet did not enhance the stress response. The results of this study indicate that HLS, diet, and the combination of HLS and diet influence estrous cycling. This has important implications for future reproductive success in the hypogravity environment of space.     

The effects of paradoxical sleep deprivation on estrous cycles of the female rats

The present purpose was to examine how sleep deprivation affects the estrous cycle of the female rat. Paradoxical sleep-deprived (PSD) adult female Wistar rats were compared to home-cage control (CTRL) on their estrous cyclicity. Forty-four PSD and forty-four CTRL female rats were distributed into 4 subgroups of 11 animals each according to the phase of estrous cycle and were subjected to sleep deprivation for 96 h by the multiple platform technique. After PSD period, vaginal estrous cycles were taken for an additional 9 days. Animals that were submitted to PSD in diestrus phase (PSD-diestrus) had their estrous cycles disrupted during the recovery period by showing a constant diestrus during the first week. As for hormone alterations, progesterone concentrations were statistically higher in PSD-diestrus compared to respective phase control and to PSD-proestrus and PSD-estrus rats while CTRL-metestrus had higher levels than CTRL-proestrus and estrus groups. Testosterone was significantly decreased in PSD-estrus in relation to PSD-proestrus and PSD-diestrus groups and was lower in CTRL-diestrus rats than in home-cage rats in proestrus. In addition, PSD-diestrus phase exhibited higher concentrations of corticosterone and lower estrogen than the respective control rats. These data indicate that PSD may modulate the ovarian hormone release through alterations in hormonal-neurochemical mechanisms.     

The anorectic effect of fenfluramine is influenced by sex and stage of the estrous cycle in rats

The controls of food intake differ in male and female rats. Daily food intake is typically greater in male rats, relative to female rats, and a decrease in food intake, coincident with the estrous stage of the ovarian reproductive cycle, is well documented in female rats. This estrous-related decrease in food intake has been attributed to a transient increase in the female rat's sensitivity to satiety signals generated during feeding bouts. Here, we investigated whether sex or stage of the estrous cycle modulate the satiety signal generated by fenfluramine, a potent serotonin (5-HT) releasing agent. To examine this hypothesis, food intake was monitored in male, diestrous female, and estrous female rats after intraperitoneal injections of 0, 0.25, and 1.0 mg/kg D-fenfluramine. The lower dose of fenfluramine decreased food intake only in diestrous and estrous females, suggesting that the minimally effective anorectic dose of fenfluramine is lower in female rats, relative to male rats. Although the larger dose of fenfluramine decreased food intake in both sexes, the duration of anorexia was greater in diestrous and estrous female rats, relative to male rats. Moreover, the magnitude of the anorectic effect of the larger dose of fenfluramine was greatest in estrous rats, intermediate in diestrous rats, and least in male rats. Thus our findings indicate that the anorectic effect of fenfluramine is modulated by gonadal hormone status.     

A detailed study on the role of sex steroid milieu in determining plasma leptin concentrations in adult male and female rats.

We examined the effects of sex steroid milieu on plasma leptin levels in adult male and female rats. Since the body weight is known to influence leptin concentrations, the hormone was measured in rats with a very similar body weight (about 250 g) throughout this study. Plasma leptin levels were significantly higher in female than in male rats. Orchidectomy (ODX) caused a significant rise in leptin, and replacement of a physiological dose of testosterone (T) completely abolished the effect of ODX. Since the effect of tamoxifen (estrogen antagonist) coadministered with T on leptin levels in ODX rats was the same as that of T alone, it was suggested that the suppressive effect of T on leptin may be mediated by the androgenic potency of T, but not by its aromatized product, estradiol. In female rats, plasma leptin concentrations did not change significantly during the estrous cycle. Furthermore, leptin levels were not affected either by ovariectomy alone or by the administration after ovariectomy of physiological doses of estradiol, progesterone, or both. This is the first study to demonstrate in rats with a very similar body weight the existence of a clear sexual difference in plasma leptin levels, and also a suppressive action of T on the adipocyte hormone concentrations.     

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.     

Urinary total polyamines levels in estrous cycle and during pregnancy in female rats

Urinary total polyamines; putrescine, spermidine and cadaverine, levels were determined in the estrous cycle and during the pregnancy in female Wistar rats. Urinary total polyamines level in 12 estrous cycles in 4 female rats revealed the definite cyclic changes, showing high levels at estrous and low levels at diestrous stage. After the ovariectomy those cyclic changes disappeared. Urinary total polyamines levels were constantly low during the first half of the pregnancy of 8 female rats, whereas the levels increase abruptly from 10 days before parturition. After fetusectomy at 15th and 17th days of the pregnancy, those levels decreased gradually. These data suggested that the urinary total polyamines levels were closely related with the pituitary-ovarian function and the growth of fetus of rats.     

Patterns of gonadotrophin secretion associated with ovulation

A detailed analysis was made of circulating luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin throughout the estrous cycle in rats. Vaginal cytology was recorded daily for 18 or 23 days in 2 groups of adult female rats, 300 and 400 per group. The presence of distended uteri or tubal ova was noted at the time of exsanguination under ether anesthesia. Serum concentrations of LH, FSH, and prolactin were determined by radioimmunoassay. In 404 rats with regular 5-day cycles, all 3 hormones reached maximum concentrations on the afternoon of functional proestrus. During the next 3 days FSH decreased progressively, and LH levels indicated a diurnal fluctuation with minimum concentrations during darkness. Serum prolactin may have b een elevated due to anesthesia and exsanguination and showed a rapid increase which occurred simultaneously with elevated LH and FSH on the afternoon of proestrus. Radioimmunoassay of all 3 hormones indicated that the increases in serum LH and prolactin did not necessarily occur simultaneously. Hypophysectomy and sequential heart puncture of proestrus rats during maximum hormone release showed disappearance rates (half-lives) for LH, FSH, and prolactin of 20, 110, and 13 minutes, respectively.     

Hormonal control of precopulatory sebaceous scent marking and ultrasonic mating vocalizations in male rats

The effects of testosterone (T) and its major metabolites, estradiol (E2) and dihydrotestosterone (DHT), on the restoration of sebaceous scent marking and 50-kHz ultrasonic vocalizations in male rats were measured in two studies (Experiments 1 and 2) employing different hormone levels. Silastic capsule administration of high and low doses of T (10 and 20 mm) or E2 (5%; 5 and 10 mm) completely restored marking to precastration levels. Both doses of DHT (30 and 40 mm) or no hormone replacement were without effect when tested in presence of estrous odor cues. In our testing paradigm, males appeared to mark glass objects with a sebaceous secretion rather than urine. Only the high dose of T (20 mm) restored vocalizations to intact levels, while animals receiving the high or low dose of E2 or DHT showed no restoration of behavior. In Experiment 3, habituation to estrous odor cues over weekly tests was not observed for marking or vocalizations. These results are discussed with respect to similarities and differences in the hormonal control of signaling behaviors by androgen metabolites in male rodents.     

Respiratory and cardiovascular effects of thyrotropin-releasing hormone as modified by isoflurane, enflurane, pentobarbital and ketamine

Thyrotropin-releasing hormone (TRH) possesses significant arousing and cardio-respiratory stimulant actions. The effects of a 2 mg/kg i.v. bolus dose of TRH on respiration and systemic hemodynamics were compared in conscious, freely-moving rats and during anesthesia with 4 different anesthetics. Fifty-four male Sprague-Dawley rats weighing 285 +/- 4 g (mean +/- S.E.M.) were divided into 5 groups: conscious, enflurane (2%), isoflurane (1.4%), pentobarbital (8 mg/kg/h i.v.), and ketamine (60 mg/kg/h i.v.). Anesthetized rats were intubated and breathed oxygen or anesthetic/oxygen spontaneously. Aortic blood pressure, heart rate, cardiac output, respiratory rate, arterial blood pH, blood gases, lactate and glucose were measured, and data were collected over a 20 min baseline period and for 130 min post-TRH. TRH increased respiratory rate in all groups; concomitant changes in arterial PCO2 indicated increased minute ventilation in the inhalation agent groups but not in the i.v. anesthetic groups or in the awake group. Significant respiratory depression in the enflurane group was rapidly reversed by TRH. The respiratory stimulant and arousing effects of TRH were smallest with ketamine anesthesia. The hemodynamic responses to TRH were consistent with a pattern of sympathoadrenalmedullary activation and were relatively uniform across groups despite anesthetic-induced alterations in baseline values. TRH or its analogues may prove useful as an analeptic in clinical anesthesia.     

The mammary tumor response in triazine-treated female rats: a threshold-mediated interaction with strain and species-specific reproductive senescence.

Triazine herbicides are among the most heavily used agricultural pesticides. Although they possess a very low acute toxicity in animals, a mammary tumor response has been consistently observed in Sprague-Dawley (SD) female rats following chronic oral dosing of atrazine and simazine at and above maximum tolerated doses. However, a substantial collection of detailed research has clearly shown that triazines are not genotoxic or mutagenic, nor do they possess estrogenic agonist activity that might promote mammary tumor growth. Examination of estrous cycling records of atrazine-treated SD rats revealed a premature appearance of persistent estrous episodes, beyond the prevalent occurrence normally seen in untreated, aging SD rats. A significant correlation has been found between early or severe estrous cycle disruption of atrazine-treated rats and the early appearance of mammary tumors. In studies using SD female rats fed atrazine for 6 months, then ovariectomized and administered an estrogen-containing silastic s.c. implant, a deficient luteinizing hormone surge was observed at a 400 parts per million (ppm) dose, but not at 25 or 50 ppm. Because SD rats exhibiting persistent estrus also have a prolonged elevation of estrogen secretion, it is proposed that the triazine-associated mammary tumor response is promoted by the test animal's own estrogen from ovarian follicles that fail to ovulate because gonadotropin surge sufficiency is blocked by the high dose of herbicide. It is further proposed that, because reproductive senescence in SD rats is fundamentally different from menopause in women, the animal response to dosing, as well as the enormous requisite dosing level, establishes a safety margin of very low risk to human health from this mode of action.     

Decreases in vaginal acyclicity of rats when housed with female hamsters

The effect of the presence of female hamsters on female rat reproductive cycles was assessed. This was accomplished by maintaining two colony rooms, one of which contained only female rats, whereas the other contained both female rats and female hamsters; the estrous cycles of female rats in these rooms were compared. Rats in the rat-hamster room displayed fewer periods of acyclicity than did rats in the rat-alone room. These data indicate that there can be interspecific effects on the periodicity of the rat reproductive cycle.     

The effect of feeding endophyte infected tall fescue seed on reproductive performance in female rats

Female Sprague-Dawley rats (Rattus norvegicus) were randomly assigned to diets containing mixtures of rat chow and tall fescue (Festuca arundinacea) seed with 0, 5, 10, 20 and 40% infection levels of Acremonium coenophialum to assess the effect of the diets on the reproductive potential of rats. Rats fed 40% infected seed had decreased body weight, decreased mean percent body weight of uteri, failed to maintain normal estrous cycles and were unable to become pregnant. Animals fed a diet of 20% infected fescue seed had extended estrous cycles. There were no significant differences among the 0, 5 and 10% dietary treatments.     

Central insulin-like growth factor 1 receptors play distinct roles in the control of reproduction, food intake, and body weight in female rats

Estradiol and progesterone induction of the LH surge in ovariectomized female rats requires concurrent activation of brain insulin-like growth factor 1 (IGF1) receptors. The present study determined whether brain IGF1 receptor signaling is required for estrous cyclicity in gonadally intact female rats. A selective IGF1 receptor antagonist (JB-1) or vehicle was continuously administered into the third ventricle by osmotic minipumps. Following surgical placement of the minipumps, all rats temporarily reduced food intake, lost weight, and suspended estrous cycles. Control rats resumed cycles within a few days and exhibited compensatory hyperphagia until they returned to presurgical body weight. Animals receiving JB-1 had severely delayed or absent estrous cycles, failed to show rebound feeding, and regained body weight more slowly. Vehicle-infused animals pair fed to JB-1-treated rats had even lower body weights but resumed estrous cycles sooner than those given drug alone. Chronic infusion of IGF1 alone had no effect on any of these parameters, but coinfusion of IGF1 with the antagonist completely reversed JB-1 effects on food intake and estrous cyclicity and partially reversed the effects on body weight. There were no significant differences in the expression of galanin-like peptide (Galp) or Kiss1 mRNA in the arcuate or periventricular hypothalamic area of control and JB-1-treated animals at a time point when food intake and estrous cycles were different between controls and JB-1-treated rats. These data suggest that brain IGF1 signaling is necessary for normal estrous cycles as well as compensatory hyperphagia and that IGF1 modulation of the reproductive axis is not secondary to reduced food intake.     

Endocrine disrupting effect of di-(2-ethylhexyl)phthalate on female rats and proteome analyses of their pituitaries

Di-(2-ethylhexyl)phthalate (DEHP) is a plasticizer and a ubiquitous environmental contaminant that may have adverse effects on human reproductive health. We examined the long-term exposure effects of DEHP on female rats and observed a strong effect on estrous cyclicity that produced a continuous diestrous stage. We found that the serum estradiol, follicle-stimulating hormone (FSH), pituitary FSH and luteinizing hormone levels were significantly reduced in the treated rats. To examine on the endocrine disrupting effects, we performed proteome-based analyses of their pituitaries, and found two proteins with remarkably reduced their levels. They were identified as the valosin-containing peptide/p97 (VCP/p97) and UMP-CMP kinase and their average protein spot intensities on statistical analysis of the spots differences of the treated/control rats were 0.13 and 0.21, respectively. Furthermore, there were 14 other proteins that had significantly changed levels, and their average protein spot intensities were in a range of 0.26 to 0.50 in 13 proteins and 2.74 in one. The reduction of in level of 7 proteins seems to be related to the intracellular protein transporting pathway, and it appears to suggest a slow down of gonadotrophin-releasing capability. Reduction of gonadotrophin release in the pituitary seems to lead to a decrease of serum estradiol level and continuous diestrous stage in estrous cyclicity.     

Hypothalamic Neuroendocrine Functions in Rats with Dihydrotestosterone-Induced Polycystic Ovary Syndrome: Effects of Low-Frequency Electro-Acupuncture

Adult female rats continuously exposed to androgens from prepuberty have reproductive and metabolic features of polycystic ovary syndrome (PCOS). We investigated whether such exposure adversely affects estrous cyclicity and the expression and distribution of gonadotropin-releasing hormone (GnRH), GnRH receptors, and corticotrophin-releasing hormone (CRH) in the hypothalamus and whether the effects are mediated by the androgen receptor (AR). We also assessed the effect of low-frequency electro-acupuncture (EA) on those variables. At 21 days of age, rats were randomly divided into three groups (control, PCOS, and PCOS EA; n = 12/group) and implanted subcutaneously with 90-day continuous-release pellets containing vehicle or 5α-dihydrostestosterone (DHT). From age 70 days, PCOS EA rats received 2-Hz EA (evoking muscle twitches) five times/week for 4–5 weeks. Hypothalamic protein expression was measured by immunohistochemistry and western blot. DHT-treated rats were acyclic, but controls had regular estrous cycles. In PCOS rats, hypothalamic medial preoptic AR protein expression and the number of AR- and GnRH-immunoreactive cells were increased, but CRH was not affected; however, GnRH receptor expression was decreased in both the pituitary and hypothalamus. Low-frequency EA restored estrous cyclicity within 1 week and reduced the elevated hypothalamic GnRH and AR expression levels. EA did not affect GnRH receptor or CRH expression. Interestingly, nuclear AR co-localized with GnRH in the hypothalamus. Thus, rats with DHT-induced PCOS have disrupted estrous cyclicity and an increased number of hypothalamic cells expressing GnRH, most likely mediated by AR activation. Repeated low-frequency EA normalized estrous cyclicity and restored GnRH and AR protein expression. These results may help explain the beneficial neuroendocrine effects of low-frequency EA in women with PCOS.     

Stimulation of estradiol-17 beta secretion by 7,12-dimethylbenz (a) anthracene during mammary tumor induction in Sprague-Dawley rats

Testosterone, androstenedione, progesterone, 17-hydroxyprogesterone, estrone and estradiol-17 beta serum levels were measured at given times after dimethylbenz (a) anthracene (DMBA) treatment of a sensitive rat strain Sprague-Dawley (S-D) and a resistant strain Wistar (W). Tumors appeared with a 100% incidence around the 14th to 15th estrous cycle after DMBA treatment in in Sprague-Dawley rats. Hormonal determinations were made, during the 5th or 6th estrous cycle after DMBA treatment, in groups of 4-day cycling rats of both strains which were given DMBA or the carrier solution (sesame oil) when they were about 55-days old. In Sprague-Dawley female rats, DMBA treatment significantly stimulated estradiol-17 beta and estrone preovulatory surge on proestrous days. No such stimulation was found for any other steroid at any time of the estrous cycle. On the other hand, the resistant Wistar rats did not show any disturbed preovulatory or basal steroid hormone release after the carcinogen treatment. These results complete and explain previous findings concerning the hypothalamo-pituitary activity after DMBA treatment of S-D rats: an early and persistent alteration in the centers involved in the hormonal cyclicity of the hypothalamo-pituitary-ovarian axis must be a result of the DMBA treatment. This deregulation could probably account for the distant and selective production of tumors in the mammary gland induced by a single gastric administration of DMBA.     

Physiological pineal effects on female reproductive function of laboratory rats: prenatal development of pups, litter size and estrous cycle in middle age

The present study investigates whether and how the pineal or its hormone melatonin influences female reproductive functions, namely the litter size, prenatal development of offsprings, and estrous cyclicity, especially its age-related cessation in a non-seasonal breeder, the laboratory rat. Wistar rats were maintained under a 24 h light-dark (12Lratio12D) cycle. Female rats were divided into 3 groups: non-operated (NO), sham-operated (SX), and pinealectomized (PX). Surgeries were performed in 35-40 day-old females. Starting at an age between 70 days and 7 months, female rats of all 3 groups were repeatedly mated with intact males. PX mothers more frequently delivered pups with malformations (e.g., taillessness, hydronephrosis, 7 out of 1263 pups) than control rats (0/1323; p<0.007). In the first delivery at 3 months of age, but not at later ages, PX mothers delivered more pups of lower body weight than control animals (p<0.001). Examination of vaginal smears showed that almost all female rats of the NO, SX, and PX groups had 4-day estrous cyclicity when they were young-between 60 days and 5 months of age. At an age of 17 to 18 months, most female rats of the NO and SX groups showed irregular, continuously diestrous or pseudopregnancy-like patterns, and 4-day estrous cyclicity was found in only 10% of the NO or SX animals. In contrast, about 50% of the PX rats showed 4-day estrous cyclicity at this older age (p< 0.001). Melatonin, when added to drinking water (0.4 mg/L) for 16 days during the dark phase increased the frequency of diestrous phase, except in continuously diestrous rats and very few others. This melatonin effect was strong in PX rats but relatively weak in SX rats. In conclusion, the pineal hormone appears to influence various reproductive functions and developmental processes, especially pregnancy and the timing of reproductive aging in rats. The effects of pinealectomy are more prominent at an age of 60 to 80 days (i.e., shortly after puberty) and at the beginning of the cessation of cycles in middle-aged females.     

Acute hyperglycemia induced by ketamine/xylazine anesthesia in rats: mechanisms and implications for preclinical models

The effects of anesthetic agents, commonly used in animal models, on blood glucose levels in fed and fasted rats were investigated. In fed Sprague-Dawley rats, ketamine (100 mg/kg)/xylazine (10 mg/kg) (KX) produced acute hyperglycemia (blood glucose 178.4 +/- 8.0 mg/dl) within 20 min. The baseline blood glucose levels (104.8 +/- 5.7 mg/dl) reached maximum levels (291.7 +/- 23.8 mg/dl) at 120 min. Ketamine alone did not elevate glucose levels in fed rats. Isoflurane also produced acute hyperglycemia similar to KX. Administration of pentobarbital sodium did not produce hyperglycemia in fed rats. In contrast, none of these anesthetic agents produced hyperglycemia in fasted rats. The acute hyperglycemic effect of KX in fed rats was associated with decreased plasma levels of insulin, adrenocorticotropic hormone (ACTH), and corticosterone and increased levels of glucagon and growth hormone (GH). The acute hyperglycemic response to KX was dose-dependently inhibited by the specific alpha2-adrenergic receptor antagonist yohimbine (1-4 mg/kg). KX-induced changes of glucoregulatory hormone levels such as insulin, GH, ACTH, and corticosterone were significantly altered by yohimbine, whereas the glucagon levels remained unaffected. In conclusion, the present study indicates that both KX and isoflurane produce acute hyperglycemia in fed rats. The effect of KX is mediated by modulation of the glucoregulatory hormones through stimulation of alpha2-adrenergic receptors. Pentobarbital sodium did not produce hyperglycemia in either fed or fasted rats. Based on these findings, it is suggested that caution needs to be taken when selecting anesthetic agents, and fed or fasted state of animals in studies of diabetic disease or other models where glucose and/or glucoregulatory hormone levels may influence outcome and thus interpretation. However, fed animals are of value when exploring the hyperglycemic response to anesthetic agents.     

The effect of chronic prepubertal administration of marihuana (delta-9-tetrahydrocannabinol) on the onset of puberty and the postpubertal reproductive functions in female rats

The effect of the main psychoactive component of marihuana, delta-9-tetrahydrocannabinol (THC) was investigated on the onset of puberty and on the reproductive function in female rats up to the seventy-fifth to eightieth day of life. The drug was administered i.p. at a dose of 1 microgram/kg/day between the twenty-second postnatal day and the day of vaginal opening (V.O.). The administration of THC caused a 2-day delay in V. O., and the number of ova on the day of first estrus was significantly lower in treated rats than in controls. No differences were observed in serum gonadotropin and prolactin (PRL) levels on the day of V. O. After puberty, alterations occurred in the neuroendocrine functions of animals receiving THC that persisted until adulthood: estrous cycles were irregular, the number of ova in animals killed 35-40 days after V. O. was reduced, and serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were decreased (diminution of serum FSH content was less expressed). An increase in serum PRL concentration could be demonstrated only in animals killed on the day of estrus. From these results, it might be concluded that THC administered to prepubertal rats--even in a very low dose--causes long-term irreversible alterations in reproductive functions. The importance of the fight against drug abuse is emphasized.     

Failure of high dietary fat to influence serum prolactin levels during the estrous cycle in female Sprague-Dawley rats

The influence of a 20% high-fat and a 4.5% control fat diet on circulating prolactin levels was determined during the estrous cycle of intact female rats, and during a progesterone-induced surge of prolactin in ovariectomized, estrogen-primed rats. An indwelling right atrial cannula was implanted into each rat to facilitate repeated blood sampling in conscious, undisturbed animals. No differences in serum prolactin levels were observed at any time during the estrous cycle or in the progesterone-induced surge of prolactin in rats fed either the high-fat or control fat diet. There also were no differences in the estrous cycles of rats on high- or low-fat diets. It is concluded that high dietary fat promotes mammary tumor development by a mechanism that does not involve alterations in circulating prolactin levels or of estrous cycles.