Growth In Male Rats Research Articles

Effects of methylphenidate on femoral bone growth in male rats.

The use of Methylphenidate (MP) can have adverse effects on bone growth and mineralization. This study aimed to investigate the underlying pathophysiology of MP-induced skeletal deficits in growing rats using stereological and immunohistochemical methods. Male rats, aged 4weeks, were orally treated with MP through an 8-h/day water drinking protocol. The rats (n=30) were randomly divided into three groups: MP-High Dose (30/60mg/kg/day MP), MP-Low Dose (4/10mg/kg/day MP), and control (water only). After 13weeks, the femoral bones were assessed using calliper measurements, dual-energy X-ray absorptiometry, and biomechanical evaluation. The total femur volume, cartilage volume, growth zone volume, and volume fractions were determined using the Cavalieri method. Immunohistochemical analyses were conducted using alkaline phosphatase and anti-calpain antibody staining. Rats exposed to MP exhibited significant reductions in weight gain, femoral growth, bone mineralization, and biomechanical integrity compared to the control group. The total femoral volume of MP-treated rats was significantly lower than that of the control group. The MP-High Dose group showed significantly higher ratios of total cartilage volume/total femoral volume and total growth zone volume/total femoral volume than the other groups. Immunohistochemical evaluation of the growth plate revealed reduced osteoblastic activity and decreased intracellular calcium deposition with chronic MP exposure. The possible mechanism of MP-induced skeletal growth retardation may involve the inhibition of intracellular calcium deposition in chondrocytes of the hypertrophic zone in the growth plate. In this way, MP may hinder the differentiation of cartilage tissue from bone tissue, resulting in reduced bone growth and mineralization.

Developmental programming of appetite and growth in male rats increases hypothalamic serotonin (5-HT)5A receptor expression and sensitivity.

Though it is well established that neonatal nutrition plays a major role in lifelong offspring health, the mechanisms underpinning this have not been well defined. Early postnatal accelerated growth resulting from maternal nutritional status is associated with increased appetite and body weight. Likewise, slow growth correlates with decreased appetite and body weight. Food consumption and food-seeking behaviour are directly modulated by central serotonergic (5-hydroxytryptamine, 5-HT) pathways. This study examined the effect of a rat maternal postnatal low protein (PLP) diet on 5-HT receptor mediated food intake in offspring. Microarray analyses, in situ hybridization or laser capture microdissection of the ARC followed by RT-PCR were used to identify genes up- or down-regulated in the arcuate nucleus of the hypothalamus (ARC) of 3-month-old male PLP rats. Third ventricle cannulation was used to identify altered sensitivity to serotonin receptor agonists and antagonists with respect to food intake. Male PLP offspring consumed less food and had lower growth rates up to 3 months of age compared with Control offspring from dams fed a normal diet. In total, 97 genes were upregulated including the 5-HT5A receptor (5-HT5AR) and 149 downregulated genes in PLP rats compared with Controls. The former obesity medication fenfluramine and the 5-HT receptor agonist 5-Carboxamidotryptamine (5-CT) significantly suppressed food intake in both groups, but the PLP offspring were more sensitive to d-fenfluramine and 5-CT compared with Controls. The effect of 5-CT was antagonized by the 5-HT5AR antagonist SB699551. 5-CT also reduced NPY-induced hyperphagia in both Control and PLP rats but was more effective in PLP offspring. Postnatal low protein programming of growth in rats enhances the central effects of serotonin on appetite by increasing hypothalamic 5-HT5AR expression and sensitivity. These findings provide insight into the possible mechanisms through which a maternal low protein diet during lactation programs reduced growth and appetite in offspring.

Effects of potassium bromate on male rat growth and testicular histology

ObjectiveTo investigate the effects of supplementation of potassium bromate (KBrO3) to drinking water on the growth rate, pubertal weight, testis & epididymal weights and testicular histology of growing male rats. MethodsThirty male Wizard rat [age = 21 d, mean BW = (40.0 ± 5.3) g] were used. The rats were grouped into 5 treatment groups each group consist of 6 rats. T1 was offered drinking water supplemented with 100 mg, T2 200 mg, T3 300 mg, T4 400 mg/L KBrO3 for the duration of the experiment, while the control group was offered KBrO3 free water. The BW weights were taken weekly. Eight weeks after treatment the rats were sacrificed, testes & epididymae were excised and weighted. The testes were fixed and histopathological sections of 5–6 μm were made, stained with H & E and examined under light microscope. ResultsThe results showed that the growth rate, pubertal weight, testes & epididymal weights and testicular histology of growing male rats were significantly (P < 0.001) affected with KBrO3 supplementation to drinking water. The growth rate of the control group and T1 (100 mg/L KBrO3) fit well a sigmoid pattern growth curve and no differences in their growth rates were recorded, while the sigmoid pattern of the growth curves of treatment T2, T3 and T4 was disrupted. No difference (P > 0.05) in BW between the control and T1 was recorded. However, it is clear that T2, T3 and T4 significantly (P < 0.05) reduced the BW at puberty. Furthermore treatment groups recorded significantly (P < 0.001) low testicular and epididymal weights compared to the control. Supplementation of KBrO3 to drinking water caused serious changes in testicular tissue of the rats. The treatment rats' testes had distorted or even collapsed seminiferous tubules and narrow interstitial spaces. Upon magnification the seminiferous tubules appeared very narrow, mostly devoid of spermatogenesis and with no sperms. ConclusionExposure of prepubertal rats to KBrO3 retards their growth, causes testicular hypoplasia and impairs spermatogenesis, which is a predictor of infertility or even sterility in the future.

A novel selective androgen receptor modulator (SARM) MK-4541 exerts anti-androgenic activity in the prostate cancer xenograft R–3327G and anabolic activity on skeletal muscle mass & function in castrated mice

The androgen receptor (AR) is a member of the nuclear hormone receptor super family of transcription factors. Androgens play an essential role in the development, growth, and maintenance of male sex organs, as well as the musculoskeletal and central nervous systems. Yet with advancing age, androgens can drive the onset of prostate cancer, the second leading cause of cancer death in males within the United States. Androgen deprivation therapy (ADT) by pharmacologic and/or surgical castration induces apoptosis of prostate cells and subsequent shrinkage of the prostate and prostate tumors. However, ADT is associated with significant musculoskeletal and behavioral adverse effects. The unique pharmacological activity of selective androgen receptor modulator (SARM) MK-4541 recently has been reported as an AR antagonist with 5α-reductase inhibitor function. The molecule inhibits proliferation and induces apoptosis in AR positive, androgen dependent prostate cancer cells. Importantly, MK-4541 inhibited androgen-dependent prostate growth in male rats yet maintained lean body mass and bone formation following ovariectomy in female rats. In the present study, we evaluated the effects of SARM MK-4541 in the androgen-dependent Dunning R3327-G prostate carcinoma xenograft mouse model as well as on skeletal muscle mass and function, and AR-regulated behavior in mice. MK-4541 significantly inhibited the growth of R3327-G prostate tumors, exhibited anti-androgen effects on the seminal vesicles, reduced plasma testosterone concentrations in intact males, and inhibited Ki67 expression. MK-4541 treated xenografts appeared similar to xenografts in castrated mice. Importantly, we demonstrate that MK-4541 exhibited anabolic activity in androgen deficient conditions, increasing lean body mass and muscle function in adult castrated mice. Moreover, MK-4541 treatment restored general activity levels in castrated mice. Thus, MK-4541 exhibits an optimum profile as an adjuvant therapy to ADT which may provide potent anti-androgenic activity at the prostate yet protective activity on skeletal muscle and behavior in patients.

Close relationship between the frequency of 22-kHz calls and vocal tract length in male rats

It is known that the size of the components of the sound production apparatus in mammals may affect the acoustic structure of vocalizations. Therefore, some acoustic variables such as voice frequency may change with age in association with body size and body weight increases. However, whether this relationship also applies to ultrasonic vocalizations emitted by laboratory rats has not been investigated. Thus, in the present study, we first recorded changes in three acoustic variables (mean frequency, duration, and bandwidth) of air puff-induced 22-kHz calls in male rats during their growth period and assessed the relationship between these changes and body weight gain (Experiment 1). Then we directly recorded several body size measures including components of the sound production apparatus in 6- and 12-week-old male rats and examined the correlation between these values and the acoustic variables of 22-kHz calls (Experiment 2). In Experiment 1, the mean frequency of 22-kHz calls in male rats during the growth period showed negative correlations with body weight gain, while the duration of 22-kHz calls showed positive correlations. In Experiment 2, only a close negative correlation between the mean frequency of 22-kHz calls and vocal tract length in male rats was found. These results suggest that the age-related decrease in the mean frequency of 22-kHz calls may be ascribed to anatomical elongation of the vocal tract length in association with the growth of male rats. These acoustic differences could inform the receivers about the age of the signaler.

Impaired Body Weight and Tail Length Gain and Altered Bone Quality after Treatment with the Aromatase Inhibitor Exemestane in Male Rats

Background: Estrogen deficiency induced by aromatase inhibitors may be a novel treatment modality for growth enhancement in short children, but may have adverse effects on bone, brain and reproduction. Aim: To assess growth effects and potential adverse effects of aromatase inhibition in male rats. Methods: 26-day-old prepubertal rats received intramuscular injections with placebo or the aromatase inhibitor exemestane at a dose of 10, 30 or 100 mg/kg/week [E10, E30, E100(6)] for 6 weeks, completely covering the sexual maturation phase, or with 3 weeks E100 followed by 3 weeks placebo [E100(3)]. Growth parameters and histology of the testis, seminal vesicle and brain were analyzed. Bone architecture was studied with X-ray microtomography. Results: Exemestane dose-dependently decreased body weight and tail length gain, as well as liver and seminal vesicle weights, but did not affect nose-anus length gain, growth plate width or radial growth. E100(6) decreased trabecular thickness (epiphysis and metaphysis) and number (metaphysis). Normal IGF-I levels and brain, testis and seminal vesicle morphology were observed. E100(3) resulted in decreased tail length gain only. Conclusion: Exemestane treatment during sexual maturation did not augment linear growth in male rats, but caused impaired body weight and tail length gain and osteopenia.

Effects of Active Immunization against Somatostatin or Somatostatin Analogues on Male Rat Growth

Effects of active immunization against somatostatin (SRIF) or various forms of somatostatin analogues on growth were investigated in male rats. In experiment 1, SRIF14, SRIF28, octreotide, Tyr 3 -octreotide or MK 608 were conjugated to human serum globulin and used as immunogens. Thirty-five Sprague-Dawley male rats were divided into seven groups and immunized against phosphate-buffered saline (PBS) (control 1), or one of the conjugated immunogens at five weeks of age. Booster immunizations were performed at 7, 9 and 12 weeks of age. Only SRIF14 induced the production of anti-somatostatin antibodies. There were no differences in blood GH concentration and growth performance between the SRIF14 group (with anti-SRIF antibodies) and other groups (without the antibodies). Although growth performance for the whole period was not affected by immunization with SRIF14 conjugate, daily weight gain and feed efficiency for 2 weeks after the third booster immunization were significantly improved, suggesting that the production of antibody against somatostatin can reach the minimal level for improving growth performance only after the third booster immunization in male rats. Experiment II was designed as a 2 2 2 2 2 factorial arrangement in which SRIF14 or Tyr11-SRIF14 was conjugated onto thyroglobulin or keyhole limpet haemocyanin (KLH) by glutaraldehyde or m-maleimidobenzoyl-N-hydroxysuccinimide coupling methods, and the immunization schedule was the same as experiment I. Anti-SRIF antibody titre values of the rats that received the conjugated SRIF14 or Tyr 11 -SRIF14 were higher than those injected with PBS. The levels of anti-SRIF antibody were not affected by the different coupling methods or by the different carrier proteins. In the Ag3 group treated with SRIF14 + KLH conjugate, total weight gain for the whole period and feed efficiency for 2 weeks after the third booster immunization were significantly different from other groups. Although GH concentration in blood was not changed by the production of antibody, our results show the possibility that active immunization against SRIF can improve growth performance in the male rat and SRIF14 peptide may be a potential candidate for active immunization.

Growth Hormone (GH) Deprivation Induced by Passive Immunization against Rat GH-Releasing Factor Delays Sexual Maturation in the Male Rat*

GH deprivation after passive immunization against rat GRF (rGRF) markedly affects somatic growth in male rats. Since it has been postulated that GH and probably insulin-like growth factor-I (IGF-I) might have a permissive role on sexual maturation, the effects of GH deprivation on the course of sexual maturation were tested. Male rats were treated with a potent anti-rGRF serum between 15 and 39 days of life (0.25 ml administered sc every second day). Body weight of treated rats averaged 62% of that of control (normal rabbit serum-treated) rats at 40 days of life (d), and 64% at 50 d after which age, treated rats started to grow normally. At 40 and 50 d, pituitary GH content was very much depressed (representing approximately 20% of control values at both ages), plasma GH was undetectable, and plasma IGF-I levels averaged 30% of those of control rats. At 70 d, 30 days after cessation of treatment, pituitary GH content, and IGF-I secretion were almost normal. At 40 d, testes and seminal vesicles of treated rats were small-for-age in agreement with significantly decreased plasma levels of FSH and delayed spermatogenesis characterized by the presence of only few or no spermatozoa. At 50 d, 10 days after cessation of anti-rGRF injections, progress of sexual maturation was found to be consistent with age and coincided with normalization of growth rate. At 40 and 50 d, pituitary contents of FSH and LH were severely decreased but became normal at 70 d. In conclusion, GH deprivation which markedly affected somatic growth induced a transient delay of sexual maturation. GH deficiency seems to have affected mostly the synthesis and secretion of FSH, thus producing a delay in testes growth and in the differentiation of the germinal cells. The low levels of IGF-I might also have been the cause for the delay of maturation at the pituitary and/or the gonadal levels.

Comparative changes in the lipogenic enzyme activities and in the in vivo fatty acid synthesis in liver and adipose tissues during the post-weaning growth of male rats

Changes in the specific activities of acetyl-CoA-carboxylase (ACX), malic enzyme (ME) and glucose-6-phosphate dehydrogenase (G-6-PD) were compared to changes in de novo lipogenesis measured by in vivo incorporation of [3H] of tritiated water into fatty acids of liver and of perirenal and dorsal subcutaneous adipose tissues. In the adipose tissues, the specific activities of the three enzymes rather closely followed fluctuations in the rate of fatty acid synthesis. In the liver, ACX and especially ME activities were satisfactory indicators of de novo lipogenesis; G-6-PD activity did not depend on de novo lipogenesis.

The effect of daily evening isoproterenol administration on reproductive organ growth in male rats treated neonatally with testosterone propionate.

Daily evening injections of isoproterenol extended the period of high pineal N-acetyltransferase activity and retarded the growth of testes, seminal vesicles and prostate in rats treated neonatally with testosterone propionate.

Catch-up growth in male rats after growth retardation during the suckling period.

Extract: On the day of birth pups from several dams were pooled and reallocated so that some of the dams had 8 pups while others had 16. The pups were weaned at 21 days and placed two to a cage with unlimited food and water. The pups were weighed and measured on days 3, 7, 14, 28, 35, 49, 63, 77, 91, 105, 119, and 228, whole body radiographs were also taken which enabled an assessment of skeletal maturity to be made. The experiment was continued until skeletal maturity reached 98% of the adult value in both groups.

DDT Effect on Rats Raised on Alpha-protein Rations: Growth and storage of liver vitamin A

Rats have been raised on rations containing alpha-protein as the sole source of nitrogen, and growth and liver vitamin A levels have been observed as a function of the rate of methionine supplement in the presence and absence of DDT. Increasing the level of methionine supplement in increments from zero to 4 g/kg produced a progressive increase in the growth of male rats. Females showed maximum growth when the methionine level was 1.0 g/kg. In the absence of added methionine DDT depressed growth, but at levels greater than 1.0 g/kg DDT stimulated growth. The level of vitamin A stored in the liver was depressed by feeding DDT, with the response being dependent on the level of methionine in the diet. The most pronounced reduction was observed with the unsupplemented ration, and the DDT effect was virtually eliminated when methionine was added at a level of 4 g/kg. A mechanism has been proposed for this interaction based on the action of DDT and methionine on the processes responsible for the absorption and transport of vitamin A.

Character of function and size in kidney during normal growth of rats.

Extract: During normal growth in male rats (3 weeks to 3 months of age) weighing from 50–400 g, kidney weight and glomerular filtration rate (GFR) increased at slower rates than did body weight; in contrast, the rate of increase in kidney weight and glomerular filtration rate were the same, and the ratio of GFR:g kidney weight was constant after 4–5 weeks of age. The ratio of maximal glucose reabsorption (TmG) to GFR increased only slightly with growth. Na-K-dependent ATPase activity/mg light microsomal protein from kidney cortex and QO2 did not change during growth. Kidney growth up to 200 g body weight at 16 weeks of age was due more to an increase in cell number; beyond then it was due more to an increase in cell size. The pattern of function-structure relation during growth differed from that observed in kidney hypertrophy secondary to uninephrectomy. It was not specifically determined from cell number or size but from some property proportional to total protein mass or to the product of cell number and cell mass. Speculation: Tubular functions of the nephron during growth increase in proportion to each other and in proportion to total renal mass. This pattern of increase differs in several respects from that which occurs following uninephrectomy. The inference is that growth response differs in fundamental biological character from the hypertrophy response.

The effect of hypothalamic lesions on sexual maturation and growth in male rats

The effect of hypothalamic lesions on sexual maturation and growth in male rats

ESTROGENS AND CORTICOIDS IN RELATION TO MAMMARY GLAND GROWTH IN MALE RATS.

SummaryThe reaction of the mammary glands to testosterone propionate (Tp) was studied in gonadectomized (gdx), adrenalectomized (adx) rats given estrone (E) and cortisone acetate (Ca) singly or together. Compared with controls with intact adrenals the mammary responses to Tp were reduced alter adrenalectomy. With few exceptions alveolar lobules failed to develop in gdx adx rats injected with 0.1 mg Tp every other day. When daily injections of 0.125 mg Ca were added to the treatment with 0.1 mg Tp the number of glands presenting alveoli increased slightly. E, 0.05 μg daily, failed to modify the mammary response to 0.1 mg Tp. Combined treatment with Ca, 0.125 mg, and E, 0.05 μg, daily and Tp, 0.1 or 0.2 mg, every other day resulted in development of alveolar lobules in a great majority of mammary glands of gdx adx rats. The findings support the view that the mammary response to androgens is dependent on concomitant actions of estrogens and adrenal cortex steroids.

Influence of androgen on hypothyroidism in rats. II. Effects of testosterone propionate on thyroidectomized rats.

The effect of TP on the growth of intact and thyroidectomized rats was essentially similar to that of MAD, i. e., the growth of male rats was never accelerated, and sometimes depressed, whereas the growth of females was always stimulated. This effect of TP, however, was smaller than MAD, in spite of its much stronger androgenic action.

Significance of the Protein Level in Synthetic Diets

SummaryIt has been reported by McIntire et at. that a diet containing 18% purified casein and 6 pure B factors does not support optimal growth in male rats, and that the missing factor is present in liver extract. Evidence is presented to show that the factor, whatever it is, may not easily be found in the usual concentrated sources of B complex, but rather that it is associated, whether as an impurity or an essential amino acid, with protein of good quality.

The Nutritional Value of Milks—Raw vs. Pasteurized and Summer vs. Winter

Summary Rats started on experiment in October and grown on mineralized raw milk and mineralized pasteurized milk showed no differences in growth or development over a period of 30 weeks. The average daily gains during the first six weeks for rats on mineralized raw milk were less for the animals started in April than those started in October. In April the rate of growth for rats on pasteurized milk was inferior to that obtained on raw milk. A decrease was observed in the daily rate of growth in male rats on mineralized milk from 19gm. for milk produced in October to 3.32gm. for milk produced in December to 2.45gm. for milk produced in February. The decrease for male rats on pasteurized milk for the same periods was 3.90 to 1.96 and to 1.14gm. The female rats showed some decrease in growth on winter milk but the impairment in. growth during this period was not nearly as great as that, observed in the case of the male rats. The kind of feed ingested by the cow has a greater effect upon the nutritive value of milk than does pasteurization. Pasteurization has practically no detrimental effect, as measured with rats, upon the nutritive value of a milk of high nutritive quality but may further decrease the value of a milk of low nutritive quality.