The effects of diazepam on fear extinction in nulliparous and primiparous female rats.

Benzodiazepines undermine the success of exposure therapy in humans with anxiety disorders, and impair the long-term memory of fear extinction (the laboratory basis of exposure therapy) in rodents. However, most rodent studies on fear extinction and benzodiazepines have been conducted in male rodents. In female rodents, the estrous cycle influences the consolidation of fear extinction memories and sensitivity to benzodiazepines. In addition, pregnancy leads to long-term changes in the neurobiological, hormonal, and behavioural features of fear extinction, as well as the responsivity to benzodiazepines. Therefore, the present experiments examined the impact of benzodiazepines on fear extinction in female rats with and without reproductive experience. Age-matched nulliparous (no reproductive experience) and primiparous (one prior reproductive experience; tested one-month post-weaning) rats received fear conditioning to a discrete cue. The next day, rats were administered the benzodiazepine diazepam (2 mg/kg, s.c), or vehicle, prior to or immediately after extinction training. Rats were then tested the next day, drug free, for extinction retention. Similar to previous findings in males, diazepam impaired extinction retention in both nulliparous and primiparous rats when administered either pre- or post-extinction training. These findings may have potential clinical implications as they suggest that benzodiazepine use in conjunction with exposure therapy may undermine long-term treatment success in women with and without reproductive experience, although this remains to be tested in human populations. Moreover, these findings are theoretically important when considered in light of previous studies showing dissociable mechanisms of fear extinction in females pre- versus post-pregnancy.

Asprosin-induced alterations in female rat puberty and reproductive hormonal profiles.

OBJECTIVE: To investigate the comprehensive effects of daily chronic asprosin administration on various pubertal and reproductive parameters in female rats. This study aims to elucidate the role of asprosin in regulating the onset of puberty and its influence on hormonal profiles and ovarian histology. METHODS: Asprosin was administered intraperitoneally (i.p.) at a dose of 500 ng/kg daily for eight weeks. Hormonal assays and histological analyses were performed to evaluate the effects of asprosin on the onset of puberty and reproductive function. RESULTS: Daily chronic administration of asprosin accelerated the onset of the first oestrus. Hormonal assays revealed significant elevations in serum levels of Follicle-Stimulating Hormone (FSH) and Oestradiol (E2), while Inhibin B levels decreased. Histological evaluations demonstrated an increased number of primary and secondary follicles in ovarian tissue, without affecting primordial follicle counts or reproductive organ weights. CONCLUSIONS: Role of adipokines in regulating puberty and reproductive function has increasingly gained recognition. This study aimed to provide the first comprehensive examination of the effects of daily chronic asprosin administration on pubertal and reproductive parameters in female rats. Utilising hormonal assays and histological analyses, asprosin was administered intraperitoneally (i.p.) at a dose of 500 ng/kg, daily, for eight weeks. Our findings revealed that daily chronic administration of asprosin accelerated the onset of the first oestrus. Hormonal assays showed significant elevations in serum levels of Follicle-Stimulating Hormone (FSH) and Oestradiol (E2), while Inhibin B levels decreased. Histological evaluations demonstrated an increased number of primary and secondary follicles in ovarian tissue, without affecting primordial follicle counts or reproductive organ weights. These results provide new insights into asprosin's role in advancing the age of first oestrus and modulating hormonal profiles, thereby offering potential benefits to the female reproductive system.

Diabetes mellitus and female sexual response: what do animal models tell us?

BACKGROUND: One of the less explored effects of diabetes mellitus (DM) is female sexual dysfunction. Females of different species have been used as models. AIM: To analyze the information of animal models of DM and female sexual response (FSR). METHODS: The literature of FSR in models of DM was reviewed. OUTCOMES: Paradigm- and diabetes-dependent changes have been found in various aspects of the FSR. RESULTS: Females in a type 1 DM (DM1) model show a decrease in the number of proestrus events, and ovariectomized females treated with sex hormones have been used. In these females, a reduction in lordosis has been reported; in proceptivity, the data are contradictory. These females present a decrease in sexual motivation that was restored after exogenous insulin. In the type 2 DM (DM2) model, females show regular estrous cycles, normal levels of lordosis behavior, and, depending on the paradigm, decreased proceptivity. These females display normal preference for sexually active males or their olfactory cues when having free physical contact; they lose this preference when tested in paradigms where physical interaction is precluded. CLINICAL TRANSLATION: Preclinical data showing the high deleterious effects of a DM1 model and the less drastic effects under a DM2 model are in accordance with clinical data revealing a much higher prevalence of sexual dysfunction in women with DM1 than DM2. STRENGTHS AND LIMITATIONS: The main strength is the analysis of the changes in various components of FSR in 2 models of DM. The main limitation is the difficulty in extrapolating the data on FSR from rats to women and that most studies focus on evaluating the impact of severe or chronic-moderate hyperglycemia/hyperinsulinemia on the sexual response, without considering other pathophysiologic alterations generated by DM. CONCLUSION: Females with severe hyperglycemia have a decrease in FSR, while those with moderate hyperglycemia show much less drastic effects.

Age-related decline in social interaction is associated with decreased c-Fos induction in select brain regions independent of oxytocin receptor expression profiles.

Social behavior decreases with aging, and we have previously found a substantial decline in social investigative behavior of old female rats. In this study we examined the neural activation pattern (c-Fos mRNA) of young (3 month) and old (18 month) female rats after brief 10 min exposure to a novel female rat in order to identify forebrain regions that show selective age-related alterations in their neural response to social investigation. We also measured relative oxytocin receptor expression (Oxtr mRNA) as a possible factor in age-related declines in c-Fos induction after social interaction. Young rats exposed to a social partner had a greater c-Fos mRNA response than those exposed to novel context alone in the lateral septum and septohypothalamic area, with blunted increases evident in old rats. In addition, c-Fos mRNA levels in the lateral septum were positively correlated with social investigative behavior. Interestingly, age-related differences in c-Fos gene induction were unrelated to the local amount of Oxtr expression within specific brain regions, although we found an age-related decline in Oxtr expression in the ventromedial hypothalamus. This functional neuroanatomical characterization may point to certain brain regions that are especially sensitive to age-related declines associated with social interaction behavior.

The Effects of Melatonin Alone or in Combination with Zinc on Gonadotropin and Thyroid Hormones in Female Rats.

Thyroid and gonadotropin hormones play an essential role in the regulation of regulating various physiological functions. The effects of melatonin and zinc (Zn) on these hormones have already been investigated. The aim of the present study was to investigate the effect of melatonin with and without zinc on the levels of gonadotropin hormones and thyroid hormones (triiodothyronine (T3), thyroxine (T4) and thyroid-stimulating hormone (TSH)) in female rats. In general, 35 sexually mature female rats were randomly divided into five treatment groups, with each group comprising 7 rats, in a completely randomized design (CRD) during the research. The rats were treated daily with Zn and melatonin via gavage as follows T1 (control 1, basal diet), T2 (control 2, treatment with normal saline) and the other experimental groups, including T3, T4 and T5, were treated with Zn (40 ppm), melatonin (5 mg/kg) or a combination of Zn and melatonin at the same dose. The administration of the drugs was continued for 20 days (daily) . Plasma samples were then taken for the determination of LH, FFH, LH/FSH, estrogen, progesterone, T3, T4 and TSH levels. The results showed no significant differences in FSH and LH levels between treatments. Estrogen, progesterone and TSH levels were higher in the rats receiving 5 mg melatonin per day than in the other groups, but not statistically significant (P>0.05). However, T3 levels decreased significantly in the group receiving 40 mg/kg Zn compared to the other experiments. (P<0.05). The results showed no significant difference between the treatments in terms of T4 levels (P>0.05). In conclusion, no remarkable changes in other variables were observed in female rats receiving melatonin, Zn or a combination of melatonin and Zn, with the exception of T3.

Effect of Precocious Puberty on Glucose and Lipid Metabolism in Female Rats / 中山大学学报(医学科学版)

ObjectiveTo explore the effect of precocious puberty on glucose metabolism and lipid metabolism in female rats. MethodsSixty two-day-old female rats were randomly divided into 2 groups. When aged 5 days， the precocious puberty group and normal group were given a single subcutaneous injection of danazol and solvent soybean oil respectively. The vaginal opening of rats was monitored from their 21 days of age. After 12 hours of fasting， all successful modeling rats were randomly executed within 3 days after vaginal opening， when aged 7 and 12 weeks. Then we measured the rats’ body weight and length， determined the concentrations of glucose， insulin， blood lipids， estradiol， leptin and adiponectin with enzyme-linked immunosorbent assay and observed the pathological changes of perirenal fat， uterus and ovary. ResultsFor body weight and length， rats in the precocious puberty group were smaller than those in the normal group within 3 days after vaginal opening， but which did not affect their subsequent growth and development， and there was no significant difference between the two groups at 7 and 12 weeks of age. Within 3 days after vaginal opening， insulin levels had significant difference between the two groups （P = 0.001）， the precocious group showed hyperinsulinemia and increased number of perirenal adipocytes. At three execution times， no significant difference was noted in estradiol， leptin and adiponectin levels between the two groups. The same was true in the ratios of ovary or uterus to body weight between the two groups. ConclusionsPrecocious puberty makes earlier onset of pubertal development and allows body maladaptation to the sudden changes of the internal environment. However， the changes due to precocious puberty are temporary and reversible， and they may become normal in adulthood.

Reproductive physiology, and physical and sexual development of female offspring born to diabetic dams / Desenvolvimento físico, sexual e fisiologia reprodutiva da prole feminina de ratas diabéticas

OBJECTIVES: The objective of this study was to evaluate physical and sexual development and reproductive physiology in female rat offspring that developed in hyperglycemia conditions in utero and during lactation. MATERIALS AND METHODS: Maternal diabetes was induced in female rats by a single IV injection of streptozotocin before mating. Female offspring development was evaluated by means of the following parameters: physical development; age of vaginal opening and first estrus; weight and histological evaluation of uterus and ovaries; duration of the estrous cycle, sexual behavior, and fertility after natural mating. RESULTS: In the female offspring, maternal diabetes caused delays in initial physical development; diminution in ovary weight and number of follicles; and inferior reproductive performance compared with the control group. CONCLUSIONS: The exposure to hyperglycemia in uterus and during lactation caused delays in physical and sexual development, and affected the reproductive physiology of female rats negatively.

OBJETIVOS: O objetivo deste estudo foi avaliar o desenvolvimento físico e sexual e a fisiologia reprodutiva de ratas que se desenvolveram em condições hiperglicêmicas in utero e lactação. MATERIAIS E METODOS: Para induzir o diabetes nas ratas, foi utilizada estreptozotocina em dose única via intravenosa antes do acasalamento. A prole feminina foi avaliada por meio dos seguintes parâmetros: o desenvolvimento físico; a idade de abertura vaginal e do primeiro estro, peso e avaliação histológica do útero e ovários; a duração do ciclo estral, o comportamento sexual e a fertilidade após acasalamentos naturais. RESULTADOS: O diabetes materno provocou, na prole feminina, retardo no desenvolvimento físico; diminuição do peso dos ovários e do número de folículos; a performance reprodutiva foi inferior à do grupo controle. CONCLUSÕES: Concluiu-se que a exposição aos meios intrauterino e lactacional hiperglicêmicos provocou retardo no desenvolvimento físico e sexual e prejudicou a fisiologia reprodutiva de ratas.

Effects of exogenous estrogen on the distribution of nitric oxide synthase positive neurons in supraoptic nuclus of hypothalamus of ovariectomized female rats / 解剖学报

Objective To observe how exogenous estrogen influences the distribution and the expression of NOS positive neurons in the supraoptic nuclei of hypothalamus in the overiectomized female rats. Methods The 2-3-month-old female rats(n=40) were selected as the healthy and nulli-copulatory experimental animals. Rats were divided into following groups: normal control group(n=10), ovariectomized control group(n=10), and two experimental groups that have been injected with estrogen for post-operative 40 days(n=10) and for post-operative 70 days(n=10). Finally, all the animals were infused and the brains were removed. Immunohistochemical (SABC) method was adopted to count the number of NOS poitive neurons and observed the NOS poitive neuronal morphology under the light microscope. The image analysis system was used to test the average gray value of immunoreactivity in NOS positive neurons. Results In the ovariectomized control group, the density of NOS positive neurons in supraoptic nucleus was significantly increased and their shapes were bigger than that of the normal control group(P<0.05). The density and the form of the NOS positive neurons in supraoptic nucleons had no apparent difference between the estrogen for post-operative 40 days group and the ovariectomizeed control group(P>0.05).In the group after estrogen-injection 2 months compared with the normal control group, and the ovariectomized control group, both of the NOS positive neurons' density and the size become significantly decreased, and the staining of cells was lesser in the group injected with estrogen for post-operation 70 days. Conclusion The present results suggest that exogenous estrogen may influence the distribution and the expression of NOS positive neurons in supraoptic nucleus of hypothalamus of ovariectomized female rats.

Effects of running exercise on the hippocapal formation and the myelinated nerve fibers in the hippocampal formation of mid-aged rats / 解剖学报

ObjectiveTo investigate the effects of exercise on the hippocampal formation and the myelinated nerve fibers in the hippocampal formation of middle-aged rats. MethodsTen 14-month female SD rats were randomly divided into exercise group and sedentary group.Rats in the exercise group were forced to run on a treadmill for 4 months. After 4 months, spatial learning capacity of two group rats was tested using the Morris water maze.Then, the hippocampal formation and the myelinated nerve fibers in the hippocampal formation were quantitatively estimated using transmission electronic microscopy and stereological techniques. Results Treadmill running enhanced the spatial learning capacity of the rats. The volume of hippocampal formation and the total length of the myelinated nerve fibers in the hippocampal formation were significantly increased after 4 months exercise.However,there was no significant difference in the total volume of the myelinated fibers in the hippocampal formation between the two groups.The absolute distributions of the total length of the myelinated fibers in the hippocampal formation of two groups indicated that the exercise-induced increase of the total length of the myelinated nerve fibers in the hippocampal formation was mainly due to the increase of the myelinated fibers with small diameter. Conclusions Four months running exercise remarkably influence the spatial learning capacity,hippocampal formation and the myelinated fibers in the hippocampal formation of the middle-aged famale SD rats. The present results reveal a potential mechanism for the fact that exercise might improve brain function.

Effects of short-term enriched environment on the hippocampal formation and the myelinated fibers in the hippocampal formation of mid-aged female rats / 解剖学报

ObjectiveTo investigate the effects of short-term enriched environment on the hippocampal formation and the myelinated fibers in the hippocampal formation of mid-aged female rats. Methods Twenty 14-month female SD rats were randomly divided into 10 enriched environment (EE) rats and 10 standard environment (SE) rats. EE rats were reared in enriched environment and SE rats were reared in standard environment for 4 months. Then, five rats were randomly selected from each group. The spatial learning capacity was assessed with Morris water maze. The hippocampal formation and the myelinated fibers in the rat hippocampal formation were quantitatively investigated with transmission electronic microscopy technique and stereological methods. Results Short-term enriched environment enhanced the spatial learning capacity of the mid-aged female rats. The total length and total volume of the myelinated fibers in the hippocampal formation of the EE rats was significantly increased by 43.3% and 47.4%, respectively, when compared to the SE rats. There was no significant difference in the hippocampal volume and the mean diameter of the myelinated fibers in the hippocampal formation between two groups. The increase of the total length of the myelinated nerve fibers in the hippocampal formation was mainly due to the increase of the myelinated fibers with small diameter. Conclusion Short-term enriched environment had significant effects on the spatial learning capacity and the myelinated fibers in the hippocampal formation of middle-aged female rats.

Histomorphometric analysis of the response of rat skeletal muscle to swimming, immobilization and rehabilitation

The objective of the present study was to determine to what extent, if any, swimming training applied before immobilization in a cast interferes with the rehabilitation process in rat muscles. Female Wistar rats, mean weight 260.52 ± 16.26 g, were divided into 4 groups of 6 rats each: control, 6 weeks under baseline conditions; trained, swimming training for 6 weeks; trained-immobilized, swimming training for 6 weeks and then immobilized for 1 week; trained-immobilized-rehabilitated, swimming training for 6 weeks, immobilized for 1 week and then remobilized with swimming for 2 weeks. The animals were then sacrificed and the soleus and tibialis anterior muscles were dissected, frozen in liquid nitrogen and processed histochemically (H&E and mATPase). Data were analyzed statistically by the mixed effects linear model (P < 0.05). Cytoarchitectural changes such as degenerative characteristics in the immobilized group and regenerative characteristics such as centralized nucleus, fiber size variation and cell fragmentation in the groups submitted to swimming were more significant in the soleus muscle. The diameters of the lesser soleus type 1 and type 2A fibers were significantly reduced in the trained-immobilized group compared to the trained group (P < 0.001). In the tibialis anterior, there was an increase in the number of type 2B fibers and a reduction in type 2A fibers when trained-immobilized rats were compared to trained rats (P < 0.001). In trained-immobilized-rehabilitated rats, there was a reduction in type 2B fibers and an increase in type 2A fibers compared to trained-immobilized rats (P < 0.009). We concluded that swimming training did not minimize the deleterious effects of immobilization on the muscles studied and that remobilization did not favor tissue re-adaptation.

Effects of isoflavone supplementation on the bone mineral density of growing female rats

This study was focused on whether or not isoflavones affect the increase in bone mineral density of growing females. Female Sprague-Dawley rats (60 +/- 5 g) were randomly assigned to two groups and provided control diets (control group) or isoflavone-supplemented diet (IF group, 57.8 mg isoflavones/100 g diet) for 9 weeks in growing female rats. Measurements of Bone Mineral Density (BMD) and Bone Mineral Content (BMC) on the experimental animals were executed in the 3rd, 6th, 9th weeks. In result, there was no significant difference in spine BMD between the isoflavones supplemented group and the control group. But, the IF group tended to have higher BMD than the control group in between 3 and 9 experimental weeks, and the striking difference could be shown in the 6th week of feeding. In case of femur BMD, the effects of added isoflavones appeared in the 6th week of feeding, and it became intensified in the 9th week of feeding to the extent that the BMD in the IF group was significantly higher than that of the control group (p<0.05). In conclusion, isoflavone supplementation increased spine BMD per weight in the 6th week of feeding, and affected the increase of femur BMD in the 9th week. The result of the experiment implies that it affects positively the formation of spine and femur BMD of growing female rats. The study also suggests that the effects of isoflavone on the pattern of BMD formation might differ from the parts of bones.

Effects of Arginine Supplementation on Bone Mineral Density in Growing Female Rats

The aim of this study was to define an arginine effect when added to a diet. The influence of arginine supplements on bone mineral density and content were studied in young female Sprague-Dawley rats fed either an arginine supplemented diet or control diet. Twenty four rats (body weight 83 +/- 5 g )were randomly assigned to one of two groups, consuming casein or casein with supplemented arginine diet. All rats were fed on experimental diet and deionized water ad libitum for 9 weeks. Bone mineral density (BMD )and bone mineral content (BMC )were measured using PIXImus (GE Lunar Co, Wisconsin, USA )in spine and femur 3, 6, and 9 weeks after feeding. The serum and urine concentrations of Ca and P were determined. Diet did not affect weight gain and mean food intake. The serum concentration of Ca and P were not changed by arginine supplementation. Urinary Ca excretion was significantly decreased by arginine supplementation. Spine BMD was significantly increased by arginine supplementation on 3 and 6 weeks after feeding. Femur BMD was significantly increased in the group of arginine supplementation on 3, 6, and 9 weeks. Rats fed the arginine-supplemented diet had better bone mineral content than did control diet rats in the experimental period. Therefore, arginine supplementation may be beneficial on spine and femur BMD increment in growing female rats. These are thought to be associated with an ar-ginine- induced growth hormone release. The exact mechanism of this effect remains to be elucidated.

Effects of Arginine Supplementation on Bone Markers and Hormones in Growing Female Rats

An important related question is whether arginine has influence bone metabolism. The effect of arginine supplements on bone markers and related hormones were studied in young female Sprague-Dawley rats fed either an arginine supplemented diet or control diet. Twenty four rats (body weight 83 +/- 5 g) were randomly assigned to one of two groups, consuming casein or casein with supplemented arginine diet. All rats were fed on experimental diet and deionized water ad libitum for 9 weeks. Bone formation was measured by serum osteocalcin and alkaline phosphatase (ALP) concentrations. And bone resorption rate was measured by deoxypyridinoline (DPD) crosslinks immunoassay and corrected for creatinine. Serum osteocalcin, growth hormone, estrogen, insulin-like growth factor-1 (IGF-1), parathyroid hormone (PTH) and calcitonin were analyzed using radioimmunoassay kits. The weight gain and mean food intake were not affected regardless of diets. The rats fed arginine-supplemented diet had not significantly different in ALP, osteocalcin, crosslinks value, PTH, estradiol, and IGF-1 compared to those fed casein diet group. The arginine-supplemented group had significantly higher growth hormone and calcitonin than casein group. This study suggests that arginine is beneficial for bone formation in growing female rats. Therefore exposure to diet which rich in arginine early in life may have benefits for bone formation and osteoporosis prevention.

Effects of Isoflavones Supplemented Diet on Lipid Concentrations and Hepatic LDL Receptor mRNA Level in Growing Female Rats

The purpose of this study was to examine the impact of isoflavones on lipid concentrations and hepatic LDL receptor mRNA level in growing female rats. Twenty four rats (body weight 75 +/- 5 g) were randomly assigned to one of two groups, consuming control diet or isoflavones supplemented diet (57 mg isoflavones/100 g diet). All rats has been fed on experimental diet and deionized water ad libitum for 9 weeks. The concentration of triglyceride and total cholesterol were measured in serum and liver. Serum HDL cholesterol was measured. Hepatic LDL receptor mRNA level was tested by RT-PCR. Supplementation of isoflavones did not affect weight gain, mean food intake and food efficiency ratio. Serum total cholesterol and non-HDL cholesterol of isoflavones supplemented rats were significantly lower than those of control rats (p < 0.05). But hepatic cholseterol level was not influenced by supplementation of isoflavones. Hepatic LDL receptor mRNA level not significantly different between control group and isoflavones supplemented group. Therefore, isoflavones may be beneficial on serum cholesterol and non-HDL cholesterol lowering in growing female rats.

Effects of Soy Protein and Isoflavones on Bone Mineral Density in Crowing Female Rats

The purpose of this study was to examine the impact of soy protein and soy isoflavones on bone and mineral density in young female Sprague-Dawley rats. Fifty eight rats (body Weight 75+/-5 g) were randomly assigned to one of four groups, consuming casein, soy protein concentrate, soy protein isolate (57 mg isoflavones/100 g diet) or casein added isoflavones (57 mg isoflavones /100 g diet). All rats were fed on experimental diet and deionized water ad libitum for 9 weeks. Bone mineral density (BMD) and bone mineral content (BMC) were measured using PIXImus (GE Lunar Co, Wisconsin, USA) in spine and femur on 3, 6, 9 weeks after feeding. The serum and urine concentrations of Ca and P were determined. Diet did not affect weight gain and mean food intake. Food efficiency ratio was lower In soy protein groups. The serum concentration of Ca and P were not changed by soy protein and isoflavones. Urinary Ca and P excretion were not significantly different. Spine BMD was significantly increased by soy protein isolate on 3 and 6 weeks after feeding. Femur BMD was significantly increased in the groups of soy protein isolate and isoflavones adding on after 9 weeks. Therefore, soy protein with rich isoflavones may be beneficial on spine and femur BMD increasement in growing female rats.

Protective Effect of Kidney-tonifying Herbal Medicine on the Changes of Female Rat Genital System Induced by Tripterygium wilfordii Hook / 中药新药与临床药理

Objective To observe the effect of kidney-tonifying herbal medicine (KTHM) on the changes of female rat genital system induced by Tripterygium wilfordii Hook(TWH).Methods Thirty female rats with normal oestrus cycle were randomly divided into 3 groups: control group,TWH group and TWH+KTHM group. The changes of genital system in all rats were examined after 90-day feeding. Results Compared with the TWH group,oestrus cycle was normal, estrogen and progestogen level and the weight of reproductive organs increased, the ovary was big,follicle grew well with more corpus luteum and good blood supplying, endometrium was thick with hyperplastic uterine gland,and vaginal epithelium became thick and cornificated in TWH+KTHM group. Conclusion Kidney-tonifying herbal medicine can antagonize the toxic and side effects of Tripterygium Wilfordii on the genital system of female rat.

The process of bone response to running training in female growing rats / 体力科学

Physical activity in the growing period has been shown to be effective for increasing bone mass because immature bones are more sensitive than mature adult bones to the stimulation with mechanical stress. However, bone growth is not uniform and changes markedly at puberty. Therefore, the response of bone to exercise may differ according to the growth process. The purpose of the present study was to investigate the process of the bone response to running training, and the relationship between the bone response and serum insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) levels in female rats. Thirty-three female Wistar-Imamichi rats 4 weeks of age were divided randomly into control (CON) and running training (RUN) groups for 6 and 12 weeks. Training consisted of running on a flatbed treadmill at 30 m/min for 60 min/day, 5 days/week. The bone mineral content (BMC) and bone mineral density (BMD) in the whole and five parts of the tibia were measured by a dual-energy X-ray absorptiometer (DXA) . Simultaneously, we measured serum concentrations of IGF-I, IGFBP-3, osteocalcin and 17β-estradiol. The whole tibial BMD was significantly higher in the RUN groups than in the age-matched CON groups. When BMD was analyzed at five different studied parts within the same tibia, the increase of BMD. was noted in the proximal and distal cancellous bone in the 6-week RUN group, and in the diaphysial, cortical bone, in the 12-week RUN group. Serum concentrations of osteocalcin, a marker of bone formation, were not altered by training, whereas they decreased with aging. Serum IGF-I levels in the training groups were not changed, but IGFBP-3 levels were increased significantly only in 6-week RUN rats. As a complex between IGFBP-3 and IGF-I may be more improve than free IGF-I in the bone formation, the high levels of IGFBP-3 in the 6-week RUN group may induce an increase in the activity of IGF-I. There was a significant positive relationship between serum IGF-I concentration and BMD of the whole tibia in the 6-week study, and between the IGFBP-3 level and BMD in both the 6 and 12-week studies.<BR>In conclusion, 1) the process of the skeletal response to running training is site-specific within the same bone, and 2) the increment of the IGFBP-3 level with training in the growth period may reflect the increment of tibial BMD through training.