Inherited hydrocephalus in Csk: Wistar-Imamichi rats; Hyd strain: a new disease model for hydrocephalus

Hydrocephalic rats were found in a breeding colony of Csk: Wistar-Imamichi strain rats. In males, the hydrocephalus were serious and could be detected from 7 days after birth. Survival was 3-4 weeks. In females, the hydrocephalus was moderate, there was no abnormal external appearance, and the rats were able to mature. Ventricular dilatation was excessive in males but moderate in females. The total frequency of hydrocephalus was 34.3% in both males and females. Breeding data indicated that this disease is heritable and is single dominant and X-linked (symbol, Hyd). The female moderate hydrocephalics could be detected by progeny tests without examining brain sections. No evidence of developmental anomaly was observed in the ventricles. This hydrocephalus was classified as being of the communicating type, and this strain was named the Hyd strain as an animal model for human hydrocephalus.     

Divergence of growth hormone actions on hepatic drug metabolism in the presence and absence of the pituitary gland.

Experiments were carried out to compare the effects of growth hormone on hepatic drug oxidation in normal and hypophysectomized rats. Administration of growth hormone to normal male rats lowered hepatic microsomal cytochrome P-450 content and decreased the rates of ethylmorphine n-demethylation and aniline hydroxylation. These effects were fully manifested in orchiectomized or adrenalectomized males, excluding a dependence upon endogenous steroids. Growth hormone was without effect on hepatic drug metabolism or cytochrome P-450 content in normal female rats. In contrast to its actions in animals with intact pituitary glands, administration of growth hormone to hypophysectomized rats of either sex increased the rate of ethylmorphine metabolism. Furthermore, in both males and females, aniline hydroxylation and microsomal cytochrome P-450 content were unaffected by growth hormone in the absence of the pituitary gland. Prolactin administration did not affect hypophysectomized or in normal rats of either sex. The results indicate that the nature of growth hormone actions on hepatic drug oxidation is pituitary-dependent and probably intertwined with the effects of other hormones. Furthermore, the direct physiological effects of growth hormone on hepatic mixed function oxidases seem to depend upon the substrate employed.     

Gender dependent effects of testosterone and 17β-estradiol on bone growth and modelling in young mice

This study examined the effects of estrogen (17β-estradiol) and testosterone on the growth of long bones in male and female mice, with and without gonadectomy. Weight and nose-to-tail length were determined at 3 weeks of age at time of gonadectomy, 7 days later at the onset of hormone therapy, and throughout the treatment period. Gonadectomized mice exhibited an initial weight gain during the pretreatment period but length was unaffected. Hormone treatment altered weight gain in surgical and intact animals in a gender- and hormone-dependent manner. Estradiol enhanced weight gain in intact mice, but inhibited weight gain in ovariectomized mice. Lower doses of estradiol increased weight gain in orchiectomized mice at early time points. Testosterone increased weight in intact females and males, but not in gonadectomized mice. Estradiol increased nose-to-tail length in intact females at early time points, but inhibited length in ovariectomized females at later times, and it decreased length in intact males. Testosterone increased length in normal females and normal males. Serum Ca was unaffected by ovariectomy, but orchiectomy resulted in decreased levels. Estradiol reduced serum Ca in gonadectomized animals; serum Ca was increased by estradiol treatment in intact females. Changes in tibial bone weight, ash weight and mineral composition, and relative sizes of epiphyseal and metaphyseal bone were gender-, gonadectomy- and hormone-specific. Bone weight was greater in ovariectomized mice. Ash weight per bone was comparable, but there was an increase in Ca and P content with ovariectomy. Estradiol increased bone weight, ash content, and bone Ca and P in ovariectomized and intact females. Orchiectomy alone did not alter bone weight, ash content, or Ca and P, but orchiectomized mice were sensitive to estradiol; all parameters were increased in the orchiectomized animals treated with estradiol. Analysis of the ash content and Ca and P per mg bone, rather than per bone, demonstrated estradiol and testosterone alter net bone formation, but not the amount of mineral per unit bone. Ovariectomy increased hypertrophic cartilage. While estradiol did not alter tibial area in ovariectomized mice, it caused an increase in intact females. The total amount of growth plate cartilage in ovariectomized animals was decreased by estradiol to levels typical of intact animals due to a greater decrease in the hypertrophic cartilage in the ovariectomized mice, as well as a greater increase in metaphyseal bone area. Testosterone had no effect on these parameters in the females. Orchiectomy decreased the amount of growth plate cartilage, but increased the hypertrophic zone. Estradiol increased growth plate cartilage in intact male mice, but decreased it in orchiectomized mice. This difference was also seen in the hypertrophic zone. Total growth plate cartilage and hypertrophic cartilage were increased by testosterone in intact males, whereas metaphyseal and epiphyseal bone area were decreased. The results show for the first time that there is a gender-specific response in both male and female mice to both estradiol and testosterone, whether or not the animals have been gonadectomized. For many parameters, orchiectomized mice behave like females in response to both sex steroids, indicating that the male gonad is needed for mouse bone to exhibit the male phenotypic response to estradiol and testosterone.     

Antimutagenic effect of chemosignals from isolated female house mouse on male germ cells (Mus musculus L.)

The influence of chemosignals from isolated mature females of the CBA strain on level of spontaneous and radiation-induced meiotic disturbances in spermatocytes I of males of the same strain was studied. Using an ana-telophase method, 24-hour exposure of males to soiled bedding containing isolated females’ chemosignals was shown to lead to a significantly lower frequency of chromosomal aberrations and other meiotic disturbances in spermatocytes I as compared to males kept on clean bedding. The same effect of female chemosignals was found in the germ cells of irradiated males (4 Gr). The mechanisms and importance of the revealed antimutagenic effect of mouse female chemosignals on the male reproductive cells in the reproduction process are discussed.     

Neuroendocrine reactions to intracerebroventricular injections of arginine-vasopressin in prenatally stressed rats

We studied the effect of central vasopressinergic stimulation on the functions of the hypothalamo-pituitary-adrenal and hypothalamo-pituitary-gonadal axes in mature offsprings of female rats stressed during the last week of pregnancy (daily immobilization for 1 h). Experiments were carried out on unanesthetized rats; the blood samples were taken 20 and 40 min after intracerebroventricular injections of arginine-vasopressin (AVP). Twenty minutes after infusion of 0.5 ng of this neuropeptide dissolved in 2 μl of isotonic NaCl solution into the III cerebral ventricle, the adrenocortical reaction in prenatally stressed males was 50% smaller than that in normal animals; on the 40th min, it continued to develop but remained weaker. In prenatally stressed females, the adrenocortical reaction to central vasopressinergic stimulation was weakened. Arginine-vasopressin-induced increases in the level of corticotropin in the blood were nearly identical in both prenatally stressed and normal rats (males and females). The level of testosterone in the blood of prenatally stressed and normal males dropped sharply 20 min after intracerebroventricular injection of AVP and, on the 40th min, remained significantly lower than the basal level in males of both studied groups; prenatal stress did not influence these alterations. Our data show that vasopressinergic control is weakened in prenatally stressed male rats, and this is a significant probable reason for the decrease in the stress reactivity of the hypothalamo-pituitary-adrenal system in these animals. Neirofiziologiya/Neurophysiology, Vol. 39, No. 6, pp. 453–457, November–December, 2007.     

Influence of age, sex and hypoxia on plasma dopamine-beta-hydroxylase activity in the rat

Using rats (Wistar strain) of our own breed, we studied dopamine-beta-hydroxylase (E.C. 1.14.17.1) (DBH) activity in the plasma of animals of different ages (in correlation to sex) under normal conditions and after exposure to altitude hypoxia (corresponding to 7000 or 9000 m and lasting 20 min). The enzyme was determined by the method of Kato et al. (1974). We found that the given plasma enzyme activity was significantly higher in females than in males, throughout the whole life-span. In addition, we found that minimum activity was reached on about the 14th and 21st day of postnatal life and again on the 40th day, while maximum activity was recorded at the ages of 5, 30 and 35 days and in adult rats. In adult animals (males and females), exposure to altitude hypoxia was followed by a statistically significant increase in plasma DBH activity, which was much more pronounced in females than in males. In males, 240 min after terminating hypoxia plasma DBH activity had returned to normal, but in females it was still significantly raised; after 48 h, plasma DBH activity in females was identical to the activity before exposure to hypoxia. In rats aged 5 and 35 days, hypoxia evoked a fluctuating response. A decrease in activity immediately after terminating hypoxia was followed at 60 min by a return to normal, but at 240 min there was again a significant decrease. In 21-day-old rats, hypoxia did not induce any significant change in plasma DBH activity (the initial activity level in this group was very low).     

Effects of male sex hormones on specific uptake and release of 3H-serotonin in the rat hypothalamus in vitro]

With the use of "isotopic method" a study was made of the main parameters of functional activity of serotoninergic elements of hypothalamus--the specific uptake and release of 5-OT. The animals used were sexually mature rats castrated on the first postnatal day. In sexually mature intact males the specific uptake of 3H-5-OT by serotoninergic structures of the anterior hypothalamus was significantly lower than in females. Castration of animals on the first day of life resulted in the increase of specific 5-OT uptake in sexually mature males up to that observed in females. There were no differences between the sexes in the rate of spontaneous release of 5-OT. However, response to K(+)-depolarization in the anterior hypothalamus of intact males was significantly lower than that in females. In the hypothalamus of males castrated neonatally the amplitude of the response to the effect of the depolarizing agent was increase up to the level observed in females. By the results obtained it is indicated that elimination of the effect of male hormones on the first postnatal day results in the increase of 5-OT uptake and release in the hypothalamus of sexually mature rat males.     

Age- and sex-related changes in type-1 iodothyronine deiodinase messenger ribonucleic acid in rat liver and kidney.

To evaluate the age- and sex-related changes in Type 1 iodothyronine deiodinase gene expression in the liver and kidneys, we measured 5'-deiodinating activity and deiodinase mRNA in developing rats. The activity in the liver increased after birth, and that in neonates was approximately half that in adults. In contrast, the activity in neonatal kidneys remained very low. The relative importance of activity in male kidneys compared to the liver increased from the ages of 1 to 20 days. The male adult rat liver showed a higher level of activity than the female liver. Deiodinase mRNA in the male liver gradually increased from 1 to 20 days, in correlation with the activity. In kidneys, deiodinase mRNA was low before day 20, and there was no significant sex difference in all age groups. In orchiectomized male rats, the activity and mRNA in the liver was similar to the low levels found in females; however, the levels in the kidneys were not significantly different than those of normal males. These data suggest that the age- and sex-related changes in iodothyronine deiodinase gene expression are regulated mainly at the pretranslational level, and that the relative importance of kidneys to liver in iodothyronine deiodinase increases from birth to age 20 days due to the difference in the gene expression.     

Behavioral characteristics of female Wag/Rij rats

Behavior of male and female WAG/Rij and Wistar rats was compared in the tests assessing the level of anxiety (light-dark choice, open field) and depression-like state (sucrose intake and preference, forced swimming). Females of WAG/Rij rats like males of the same strain exhibited symptoms of depression-like behavior: increased immobility in the forced swimming test and decreased sucrose intake and preference (anhedonia). In contrast to males, females of WAG/Rij rats displayed more distinct signs of increased anxiety as compared to Wistar rats. Both WAG/Rij and Wistar females exhibited increased locomotor and exploratory activity in the open field as compared to males.     

Norepinephrine turnover in the rat pineal gland. Acceleration by estradiol and testosterone.

The administration of 0.5 mg of testosterone propionate (TP) to orchiectomized rats or of 2 ug of estradiol to oophorectomized rats resulted in significantly less ³H-norepinephrine remaining in the pineal gland 60 and 120 min after a pulse injection of the radioactive compound. This effect was not observed in animals administered with ³H-norepinephrine 45 or 180 min after a single hormone injection. Half-lives for ³H-norepinephrine disappearance in estradiol- and TP-treated rats were 62 and 60 min respectively whereas those of female and male vehicle-injected controls were 109 and 123 min respectively. Hormone treatment did not affect pinela norepinephrine content in any of the schedules used. Norepinephrine efflux expressed as pg. mg tissue⁻¹. min⁻¹ was 33 in estradiol-treated females, 17 in vehicle-treated females, 28 in TP-treated males and 12 in vehicle-treated males. These data indicate that the norepinephrine turnover in neurons innervating the pineal gland is increased by chronic administration of female and male sex hormones.     

Mediate mechanism of positive effect of estrogens on the level of corticosteroid-binding globulin in rats

The mechanism of estrogen action on CBG level in blood serum was studied in the experiments on white rats. It was shown that estradiol injection at the dose 100 micrograms for 3 weeks induced the increasing of CBG serum level in intact males, but it was not changed in the gonadectomized males and females. The presence of the positive effect of exogenic estrogens only in the intact males was connected with the estrogen depression of testis function. It suggests the absence of direct positive estrogens action on the level of CBG in the rats. The estrogen effect is not mediated by adrenal corticosteroids, and has independent negative action on CBG level in the rat. Thus, estrogen does not participate in the endocrine regulation of CBG content in the mature rats.     

The effect of pituitary homografts on the accessory sex organs and serum hormonal levels with or without androgen in mature male rats

The effect of pituitary homografts on the accessory sex organs and hormonal levels were studied in Wistar mature male rats. Grafted rats were further divided into four experiments: rats were bled once daily via a jugular vein cannula for seven days to investigate when serum prolactin began to rise after transplantation. rats were decapitated on the seventh day after transplantation to test whether 7 days were long enough to show the effect of pituitary grafts on the weight of prostate and seminal vesicles. rats were orchiectomized or orchiectomized and adrenalectomized on the seventh day after transplantation and then decapitated 4 weeks later to test a long term action of pituitary grafts and hormonal levels on the accessory sex organs without androgen. Rats grafted with several pieces of muscle were used as controls in each experiment. The initial rise in serum prolactin level was observed on the fourth day after pituitary transplantation, and then a higher serum prolactin level was maintained thereafter. Despite the higher prolactin level in the pituitary-grafted rat than in the control, no significant differences from the control in the weight of prostates and seminal vesicles and adrenal gland and the concentrations of serum luteinizing hormone (LH) and follicular stimulating hormone (FSH) were measured. This result showed that the weight of accessory sex organs was not affected by a higher serum prolactin within seven days.(ABSTRACT TRUNCATED AT 250 WORDS)     

Selected biological values of the African white-tailed sand rat (Mystromys albicaudatus)

Forty-three female and 44 male, sexually mature normal African sand rats (Mystromys albicaudatus) provided serum and urine for determining normal ranges of selected serum chemistry and electrolyte determinations and for routine nonfasted urinalyses. Serum chloride and serum glucose levels were greater and serum sodium levels lower for female rats. An unusually high physiological level of urine protein was detected, and it was determined that standard dipstick methods for determining urine protein levels in this species gave artificially high results. Ketouria and glycosuria were more common in males than in females, but these determinations were not correlated to blood urea nitrogen or to serum glucose levels. No association was found between body weight and any of the serum chemistry, electrolyte or urinalysis variables examined.     

Rat cheek gland compounds: behavioural response to identified compounds

Cheek gland secretions from sexually mature and reproductively active male and female laboratory rats (Wister strain), Rattus norvegicus albinus were analysed by gas chromatography/mass spectroscopy. Alkanes, aliphatic acids esters and alcohols were identified in the secretions. Cheek gland preparation from males contained predominantly three compounds, viz. di-n-octyl phthalate (I); 1,2-benzene diacarboxylic acid butyl (2-ethyl hexyl) ester (II); and 1,2 benzene dicarboxylic acid (2-methylpropyl) ester (III) whereas in the cheek gland of females two compounds, viz, 1,2-benzene dicarboxylic acid (2-methylpropyl) ester (I); and 2,6,10 dedecatrien-1-ol, 3,7,11-trimethyl-(Z, E) (II) were the major fractions. The identified compounds were tested for odour preferences. Compounds II and III of males and I and II of females attracted both male and female conspecifics. By contrast, compound I from males only attracted females. The level of attraction also varied from compound to compound. The results suggest that cheek gland secretions have pheromonal functions.     

Protein binding glucocorticoid hormones (transcortin) during peri-and postnatal ontogenesis and pregnancy in rats]

The constants of association and the energy of interaction between transcortin and cortisol, the binding ability and other characteristics of transcortin have been studied in the embryos, sexually immature and mature young and old females, females on the 14th and 21st days of pregnancy, immature and mature males. The constant of association in all the groups amounted to ca. 10(8) and the energy of interaction ca. 10 Cal/mole. The embryos and immature rats of both sexes are characterized by relatively low levels of the binding ability of transcortin. During the sexual maturation, the level of transcortin increased--insignificantly in males and markedly in females. The level of transcortin in the latter remained almost invariable during pregnancy and senescence. By the electrophoretic and sedimentation properties transcortin was the same in different groups. The high level of transcortin during pregnancy corresponded to the high level of hormones bound by transcortin, the level of these hormones in the embryos being much lower than in the mother.     

Do female broiler breeder fowl display a preference for broiler breeder or laying strain males in a Y-maze test?

In recent years, the commercial broiler breeder industry has reported problems of male aggression towards females [Millman, S.T., 1999. An investigation into extreme aggressiveness of broiler breeder males. Unpublished PhD Thesis, University of Guelph]. Although this aggression is shown by the males and is apparently a defect in their behaviour [Millman, S.T., Duncan, I.J.H., 2000. Strain differences in aggressiveness of male domestic fowl in response to a male model. Appl. Anim. Behav. Sci. 66, pp. 217-233], it is also possible that it stems in some way from the females. For example, broiler breeder females may not be receptive to male courtship advances, and may avoid males, thus causing frustration in otherwise normal males. The objective of this study was to examine mate preference by broiler breeder females and the effects of sexual experience on preference. A total of 24 mature, broiler breeder females were individually tested in a Y-maze, with females choosing between a broiler breeder male and a laying strain male. Females were tested using male models and tethered live males, both when the females were sexually inexperienced and after they had been housed with broiler breeder or laying strain males for 6 weeks.Females did not display a male-strain preference when tested with models, but sexually experienced females displayed some evidence of a preference for laying strain males in tests with live males, which did not reach statistical significance (P<0.10). Live males were a stronger attractant for sexually experienced females than were models (P<0.005). Individual females tested with the same pair of males showed different preferences, suggesting females used male behaviour as a basis for their choices, and not male morphology.In conclusion, we found no evidence that broiler breeder females inherently discriminate against broiler breeder males.     

Influence of gender and the endocrine environment on the distribution of androgen receptors in the lacrimal gland

Androgens are known to regulate both the structure and function of lacrimal tissue in a variety of species. To explore the endocrine basis for this hormone action, the following study was designed to: (1) determine the cellular distribution of androgen receptors in the lacrimal gland; and (2) examine the influence of gender and the endocrine environment on the glandular content of these binding sites. Lacrimal glands were obtained from intact, castrated, hypophysectomized, diabetic or sham-operated male or female adult rats, mice or hamsters, as well as from orchiectomized rats exposed to placebo compounds or physiological levels of testosterone. The cellular of androgen receptors was evaluated by utilizing an immunoperoxidase protocol, in which a purified rabbit polyclonal antibody to the rat androgen receptor was used as the first antibody. Our findings with lacrimal glands showed that: (1) androgen receptors are located almost exclusively in nuclei of epithelial cells; (2) the cellular distribution or intranuclear density of these binding sites is far more extensive in glands of males, as compared to females; (3) orchiectomy or hypophysectomy, but not sham-surgery or diabetes, lead to a dramatic reduction in the immunocytochemical expression of androgen receptors; and (4) testosterone administration to orchiectomized rats induces a marked increase in androgen receptor content, relative to that in placebo-exposed glands. Our results also reveal that a 10 kb androgen receptor mRNA exists in the rat lacrimal gland. Overall, these findings demonstrate that gender and the endocrine system may significantly influence the distribution of androgen binding sites in rat lacrimal tissue. Moreover, our results show that androgens up-regulate their own lacrimal gland receptors.     

Sex differences in adrenocortical structure and function. V. The effects of postpubertal gonadectomy and gonadal hormone replacement on nuclear-cytoplasmic ratio, morphology and histochemistry of rat adrenal cortex.

Studies were carried out on adult rats of Wistar strain. Six weeks after postpubertal gonadectomy some of the orchiectomized rats were injected with a single dose of testosterone cypionate and ovari-ctomized rats with estradiol cypionate (17 beta-cyclopentyloproprionate esters of testosterone or estradiol). The control rats were sham operated. Investigations were carried out 8 weeks after surgery. Absolute and relative adrenal weight is lower in the male than in the female rat. Orchiectomy increases these weights while testosterone restores them to their normal level. Ovariectomy has no effect on the weight of adrenal, estradiol, however, increases the relative weight of the gland. The adrenal cortex of the adult female is wider than in the adult male rat and in female gland sudanophobic zone is lacking. Orchiectomy leads to the broadening of the adrenal cortex and testosterone replacement has an opposite effect. Ovariectomy has no effect on the structure of adrenal cortex and estradiol replacement resulted in the narrowing of zona glomerulosa. There were no differences in the nuclear-cytoplasmic ratio of zona glomerulosa cells in male and Female rats and neither gonadectomy nor gonadal hormone replacement has no effect on this parameter. The nuclear-cytoplasmic ratio of zona fasciculata cells in the male is markedly higher than in female. Orchiectomy lowers this ratio and testosterone restores it to the normal level. Neither ovariectomy nor estradiol replacement has effect on the nuclear-cytoplasmic ratio of zona fasciculata cells. Similar changes as those in the zona fasciculata were observed in zona reticularis cells. Among the oxidoreductases studied, the most marked sex differences were found in alpha-glycerophosphate dehydrogenase activity. In control female rats an intense reaction for this enzyme is observed in broad band of cells of the zona fasciculata interna, while in male rats only individual cells showed this reaction. In orchiectomized rats the reaction for this enzyme is similar as in control female rats and testosterone restores it to normal. Ovariectomy has no effect on localisation of reaction while after estradiol replacement reaction was more intense. Regarding the remaining oxidoreductases studied, in the adrenal cortex of rats of both sexes no marked differences were observed in localization, however, intensity of reaction depended upon applied experimental conditions. More distinct sex differences were observed in topochemistry of some hydrolases and intensity of reaction depended upon the applied experimental conditions.     

Breeding of cataract rat strain (ICRF/Kmu//Yg)

A inbred strain, ICRF, which can be used as a model of both human cataract and epilepsy is described. The strain was bred from the ICR cataractous rat (Ihara, 1983). The original ICR strain showed bilateral cataract on 11-12 weeks of age, but the cataractous syndrome frequently disappeared during life. In the new ICRF strain the cataractous syndrome continued through the life, as shown by primary investigation of 38 males and 32 females. Besides cataract, severe epilepsy-like seizures were observed in 90% of the males. Seizures were rare in females (3%). The life span of the ICRF rats was short, 58% of the males and 6% of the females died before 52 weeks of age.     

Quantitative and qualitative gender-related differences in jejunal glutathione S-transferase in the rat effect of testosterone administration

Gender-related differences and the regulation by testosterone of glutathione S-transferase were studied in rat jejunum. We analyzed enzyme activity and the relative content of GST subunits. Four experimental groups of adult rats were studied: normal males, castrated males, castrated males injected with testosterone and normal females. Glutathione S-transferase activity was assayed using 1-chloro-2,4-dinitrobenzene and 1,2-dichloro-4-nitrobenzene as substrates. Differences in subunit composition among groups were evaluated by western blot analysis. The results demonstrated that 1-chloro-2,4-dinitrobenzene conjugation rate is higher in normal males than in normal females and castrated males. Testosterone administration to castrated males raised the activity up to the level observed in normal males. No significant difference in glutathione S-transferase activity towards 1,2-dichloro-4-nitrobenzene was observed among groups. Western blot analysis revealed that males and females differ in all subunits tested that is, rGSTA2, rGSTM1, rGSTM2 and rGSTP1, and that testosterone regulates the content of rGSTM1, rGSTM2 and rGSTP1. In conclusion, jejunal GST shows a gender-dependent regulation affecting both enzyme activity and subunit composition, and testosterone appears to be one of the factors involved.