scholarly journals Neurons and Glial Cells Are Added to the Female Rat Anteroventral Periventricular Nucleus During Puberty

Endocrinology ◽  
2016 ◽  
Vol 157 (6) ◽  
pp. 2393-2402 ◽  
Author(s):  
Margaret A. Mohr ◽  
Francisca L. Garcia ◽  
Lydia L. DonCarlos ◽  
Cheryl L. Sisk

The anteroventral periventricular nucleus (AVPV) orchestrates the neuroendocrine-positive feedback response that triggers ovulation in female rodents. The AVPV is larger and more cell-dense in females than in males, and during puberty, only females develop the capacity to show a positive feedback response. We previously reported a potential new mechanism to explain this female-specific gain of function during puberty, namely a female-biased sex difference in the pubertal addition of new cells to the rat AVPV. Here we first asked whether this sex difference is due to greater cell proliferation and/or survival in females. Female and male rats received the cell birthdate marker 5-bromo-2′-deoxyuridine (BrdU; 200 mg/kg, ip) on postnatal day (P) 30; brains were collected at short and long intervals after BrdU administration to assess cell proliferation and survival, respectively. Overall, females had more BrdU-immunoreactive cells in the AVPV than did males, with no sex differences in the rate of cell attrition over time. Thus, the sex difference in pubertal addition of AVPV cells appears to be due to greater cell proliferation in females. Next, to determine the phenotype of pubertally born AVPV cells, daily BrdU injections were given to female rats on P28–56, and tissue was collected on P77 to assess colocalization of BrdU and markers for mature neurons or glia. Of the pubertally born AVPV cells, approximately 15% differentiated into neurons, approximately 19% into astrocytes, and approximately 23% into microglia. Thus, both neuro- and gliogenesis occur in the pubertal female rat AVPV and potentially contribute to maturation of female reproductive function.

2002 ◽  
Vol 172 (3) ◽  
pp. 441-448 ◽  
Author(s):  
L Pinilla ◽  
ML Barreiro ◽  
LC Gonzalez ◽  
M Tena-Sempere ◽  
E Aguilar

Hypothalamic differentiation in the female rat during the neonatal period is critically dependent on the steroid milieu, as permanent changes in reproductive function are observed after administration of oestradiol and testosterone during such a critical stage. Selective oestrogen modulators (SERMs) constitute a family of drugs that, depending on the tissue, are able to exert oestrogenic or antioestrogenic actions. The present experiments were conducted to analyse whether the SERMs, tamoxifen and raloxifene, can cause oestrogenic actions during the hypothalamic differentiation period. Postnatal female rats were injected between days 1 and 5 with 100 microg/day tamoxifen, raloxifene or ICI 182,780 (a pure antioestrogen). Other groups of animals were injected on day 1 of age with 100 microg oestradiol benzoate (OeB) or 1.25 mg testosterone propionate (TP) alone or in combination with raloxifene (500 microg/day between days 1 and 5). In all experimental groups, the age, body weight and concentrations of serum gonadotrophins at vaginal opening were recorded, whereas vaginal cyclicity and the negative and positive feedback between oestradiol and LH were monitored in adulthood. The results obtained confirmed the ability of high doses of OeB or TP to alter the normal differentiation of the brain permanently. They also reinforced the hypothesis that oestrogens are also necessary for normal brain differentiation in female rats because administration of a pure antioestrogen, such as ICI 182,780 permanently altered the function of the reproductive axis. In addition, our data provided evidence for different actions of the two SERMs under analysis (raloxifene and tamoxifen) upon peripheral targets, as raloxifene advanced vaginal opening whereas tamoxifen did not. In contrast, their actions on brain differentiation appeared similar and analogous to those obtained after neonatal administration of oestradiol, as evidenced by vaginal acyclicity, ovarian atrophy, sterility and abolition of negative and positive feedback between oestradiol and LH, thus suggesting an oestrogenic action of these SERMs on hypothalamic differentiation. Moreover, the oestrogenic activity of raloxifene was supported by its inability to block the effects of OeB and TP administered neonatally. In conclusion, the present results indicated that the SERMs, tamoxifen and raloxifene, exert an oestrogen-like effect upon hypothalamic differentiation of the neonatal female rat.


1975 ◽  
Vol 80 (2) ◽  
pp. 319-328
Author(s):  
R. S. Leeuwin ◽  
B. J. Visser ◽  
C. v. d. Meer

ABSTRACT Using the extraction procedure of Schmidt & Thannhauser (1945) and the indole reaction for DNA according to Ceriotti (1952), the DNA content of female rat liver was about one and a half times that of male liver. Castration of male rats, with or without administration of testosterone propionate, had no effect on the liver DNA content. Spaying of female rats (5–6 weeks of age) caused a decrease of the liver DNA content. Substitution with oestradiol benzoate restored the amount of DNA. No significant sex difference was observed in the DNA content of either rat brain, kidney, spleen and thymus, or mouse liver. Dische's diphenylamine reaction showed no significant sex difference in the rat liver DNA content. It was concluded that rat liver may contain a substance which is controlled by oestrogens and which interferes with the indole reaction. The interfering factor is present in the protein fraction of the liver extract. The possible nature of this interfering substance is discussed.


2001 ◽  
Vol 144 (6) ◽  
pp. 653-658 ◽  
Author(s):  
K Ogura ◽  
M Irahara ◽  
M Kiyokawa ◽  
M Tezuka ◽  
T Matsuzaki ◽  
...  

BACKGROUND: Leptin, which is the product of the obese gene, is believed to play important roles in pubertal development and reproductive function in females. In a study using adult male rats, it was found that leptin stimulated secretion of gonadotropin from the pituitary in a dose-related manner. However, there has been no such study in female rats. OBJECTIVE: To investigate the effects of leptin on the production of LH and FSH from the pituitary in female rats, using primary cultured pituitary cells. METHODS: In this study, we determined body weight, serum leptin concentration and serum estradiol (E(2)) concentration in female Wistar rats at 3, 5, 6, 7, 9 and 11 weeks of age, and cultured pituitary cells from 6-week-old female Wistar rats with leptin (0--10(-7) mol/l) and GnRH (0 or 10(-8) mol/l). Then basal and GnRH-stimulated extra- and intracellular LH and FSH were assayed by RIA. RESULTS: Serum leptin concentration increased with increases in body weight and E(2) concentration. The pubertal serum leptin concentration was about 10(-10) mol/l. At a lower or moderate concentration, leptin produced dose-related increases in both basal and GnRH-stimulated extra- and intracellular LH and FSH in pituitary cells. At a concentration of 10 mol/l, leptin significantly (P<0.05) stimulated both basal and GnRH-stimulated extra- and intracellular LH and FSH. However, at greater concentrations, these effects diminished. CONCLUSIONS: These results indicated that leptin induced pituitary cells to produce and secrete both LH and FSH, with or without GnRH. The concentration of leptin that induced the greatest production of gonadotropins by pituitary cells was 10(-10) mol/l, which was the same as the physiological pubertal concentration. Leptin may be involved in the onset of puberty. It is also conceivable that leptin may be a cause of ovulatory failure, not only in weight loss but also in weight gain.


1971 ◽  
Vol 67 (3) ◽  
pp. 517-530 ◽  
Author(s):  
Martin Wenzel

ABSTRACT With the aid of metenolon-17α-T a tritium-transfer to oestrone in rat liver slices was demonstrated. This tritium-transfer from metenolon17α-T to oestrone yielding tritium-labelled oestradiol had a higher efficiency in male than in female rat liver. Correspondingly in the presence of metenolon the relation of oestrone to oestradiol is changed more in male than in female rat liver. Looking for biochemical differences between the anabolic steroid metenolon and testosterone the oxydation at C17 was measured in different organs of the rat using 17α-T-labelled steroids. The highest oxydation rate was found for both steroids in the liver. In the sexual organs of male rats the oxydation rate of testosterone was 50–10 times higher than that of the anabolic steroid. This difference was less in sexual organs of female rats. This result of a greater biochemical difference between both steroids in males than in females leads to the question, whether the dissociation between the anabolic and the androgen effects is higher in males than in females.


1998 ◽  
Vol 335 (3) ◽  
pp. 619-630 ◽  
Author(s):  
Philip J. SHERRATT ◽  
Margaret M. MANSON ◽  
Anne M. THOMSON ◽  
Erna A. M. HISSINK ◽  
Gordon E. NEAL ◽  
...  

A characteristic feature of the class Theta glutathione S-transferase (GST) T1-1 is its ability to activate dichloromethane and dibromoethane by catalysing the formation of mutagenic conjugates. The level of the GSTT1 subunit within tissues is an important determinant of susceptibility to the carcinogenic effects of these dihaloalkanes. In the present study it is demonstrated that hepatic GST activity towards these compounds can be elevated significantly in female and male Fischer-344 rats by feeding these animals on diets supplemented with cancer chemopreventive agents. Immunoblotting experiments showed that increased activity towards the dihaloalkanes is associated with elevated levels of the GSTT1 subunit in rat liver. Sex-specific effects were observed in the induction of GSTT1 protein. Amongst the chemopreventive agents tested, indole-3-carbinol proved to be the most potent inducer of hepatic GSTT1 in male rats (6.2-fold), whereas coumarin was the most potent inducer of this subunit in the livers of female rats (3.5-fold). Phenobarbital showed significant induction of GSTT1 only in male rat liver and had little effect in female rat liver. Western blotting showed that class Alpha, Mu and Pi GST subunits are not co-ordinately induced with GSTT1, indicating that the expression of GSTT1 is determined, at least in part, by mechanisms distinct from those that regulate levels of other transferases. The increase in amount of hepatic GSTT1 protein was also reflected by an increase in the steady-state level of mRNA in response to treatment with chemopreventive agents and model inducers. Immunohistochemical detection of GSTT1 in rat liver supported the Western blotting data, but showed, in addition to cytoplasmic staining, significant nuclear localization of the enzyme in hepatocytes from some treated animals, including those fed on an oltipraz-containing diet. Significantly, the hepatic level of cytochrome P-450 2E1, an enzyme which offers a detoxification pathway for dihaloalkanes, was unchanged by the various inducing agents studied. It is concluded that the induction of GSTT1 by dietary components and its localization within cells are important factors that should be considered when assessing the risk dihaloalkanes pose to human health.


1990 ◽  
Vol 5 (3) ◽  
pp. 267-274 ◽  
Author(s):  
I. Porsch Hällstöm ◽  
J.-Å. Gustafsson ◽  
A. Blanck

ABSTRACT Expression of the c-myc gene was studied in the livers of male and female Wistar rats. Furthermore, the effects on hepatic c-myc expression of neonatal and adult castration, with or without testosterone supplementation, as well as of continuous administration of GH to intact males, were analysed. Expression of c-myc was low in 6-day-old animals of both sexes, reached a maximum at 35 days of age and declined to the level of adult animals at 70 days. In prepubertal animals, expression was higher in females, but was higher in males after the onset of puberty, the postpubertal female rat liver exhibiting 50–70% of the expression in males. Treatment of adult male rats with bovine GH in osmotic minipumps for 1 week reduced c-myc expression to the level of female rats. Castration, both neonatally and of adults, also feminized hepatic c-myc expression. Testosterone supplementation of the castrated animals increased the expression towards the level in sham-operated controls. These results indicate that the c-myc gene is regulated by the hypothalamo-pituitary-liver axis via the sex-differentiated pattern of GH secretion, in analogy with other sex-differentiated hepatic functions, such as metabolism of steroids and xenobiotics. Neuroendocrine regulation of a gene such as c-myc, which is involved in the control of cell proliferation and differentiation, represents another aspect of the complex influence of GH on various somatic functions.


2012 ◽  
Vol 63 (4) ◽  
pp. 417-427 ◽  
Author(s):  
Mariana Tozlovanu ◽  
Delphine Canadas ◽  
Annie Pfohl-Leszkowicz ◽  
Christine Frenette ◽  
Robert J. Paugh ◽  
...  

AbstractIn the present study the photoreactivity of the fungal carcinogen ochratoxin A (OTA) has been utilised to generate authentic samples of reduced glutathione (GSH) and N-acetylcysteine (NAC) conjugates of the parent toxin. These conjugates, along with the nontoxic OTα, which is generated through hydrolysis of the amide bond of OTA by carboxypeptidase A, were utilised as biomarkers to study the metabolism of OTA in the liver and kidney of male and female Dark Agouti rats. Male rats are more susceptible than female rats to OTA carcinogenesis with the kidney being the target organ. Our studies show that the distribution of OTA in male and female rat kidney is not significantly different. However, the extent of OTA metabolism was greater in male than female rats. Much higher levels of OTα were detected in the liver compared to the kidney, and formation of OTα is a detoxification pathway for OTA. These findings suggest that differences in metabolism between male and female rats could provide an explanation for the higher sensitivity of male rats to OTA toxicity


2021 ◽  
Vol 54 (1) ◽  
pp. 52-61
Author(s):  
NR Shepelskaya ◽  
YaV Kolyanchuk

Aim. Studying the effect of generic pesticides cyproconazole (98 %) and two samples of epoxiconazole (epoxiconazole 1 — 95,75 % and epoxiconazole 2 — 98,7 %) on the reproductive system of male and female Wistar Han rats at the level of the organism when exposed during gametogenesis, identification and characterization of their hazard, as well as assessment of the risk of reproductive toxicity of these compounds. Materials and Methods. The test samples were administered daily (5 days a week) by oral gavage at doses of 0.2 and 2.0 mg/kg for cyproconazole and 0.5 and 2.0 mg/kg for epoxiconazoles during 11 weeks for males, and 10 weeks for females. Also, there were kept intact males and females, intended for crossover mating with experimental animals. After the end of the exposure, functional indicators of the state of the gonads and the ability of animals to reproduce offspring were studied. The duration and the frequency of each stage of the estrous cycle in female rats and the number of motile sperm, the total amount of sperm and the number of abnormal forms of germ cells of the male rats were studied. The reproductive function state in females was evaluated on day 20th of pregnancy. Thereby the number of corpora lutea in the ovaries, number of alive, dead and resorbed foetuses and embryos, the foetus weight, total weight of litters were registered. The studies were carried out in accordance with the recommendations of the Bioethics Commission and the Centre’s standard operating procedures, developed in accordance with the recommendations and requirements of Good Laboratory Practice (GLP). Conclusions. Test substances at a maximum dose of 2.0 mg/kg of body weight have reproductive toxicity and endocrine-disruptive effect, exerting a significant antiandrogenic effect on males and antiestrogenic effect on female rats. No-observed-adverse-effect-level (NOАEL) for gonadal and reproductive toxicity for male and female Wistar Han rats were established. They are 0.2 mg/kg body weight for cyproconazole and 0.5 mg/kg body weight for epoxiconazole. Key Words: azole fungicides, cyproconazole, epoxiconazole, reproductive toxicity, antiandrogenic and antiestrogenic effects, Wistar Han rats.


1999 ◽  
Vol 91 (5) ◽  
pp. 1447-1447 ◽  
Author(s):  
Astrid Chiari ◽  
Joseph R. Tobin ◽  
Hui-Lin Pan ◽  
David D. Hood ◽  
James C. Eisenach

Background Cholinergic agents produce analgesia after systemic and intrathecal administration. A retrospective review showed that intrathecal neostigmine was more potent in women than in men, suggesting a sex difference in this response. The purpose of this study was to determine whether such a sex difference exists in normal rats and to examine the pharmacologic mechanisms that underlie this difference. Methods Male and female rats with indwelling intrathecal catheters received injections of neostigmine, bethanechol (muscarinic agonist), or RJR-2403 (neuronal nicotinic agonist) alone or with atropine (muscarinic antagonist), mecamylamine (nicotinic antagonist), or phentolamine alpha-adrenergic antagonist) with antinociception determined to a noxious heat stimulus to the hind paw. Time versus subcutaneous paw temperature relationships were defined for males and females. Results Neostigmine produced dose-dependent antinociception with five times greater potency in female than in male rats. Neostigmine-induced antinociception was reversed in male rats by atropine and unaffected by mecamylamine, whereas it was partially reduced by each antagonist alone in females and completely reversed after injection of both. RJR-2403 was more potent in females than in males, whereas there was no sex difference to bethanechol. Phentolamine partially reversed antinociception from RJR-2403 in females. Paw temperature increased more rapidly in females than in males for the same lamp intensity. Conclusions These data demonstrate a large sex difference in antinociception to intrathecal neostigmine that is primarily the result of a nicotinic component in females. Phentolamine reversal suggests that part of this nicotinic component may rely on spinal norepinephrine release. A better understanding of this sex difference could lead to development of novel pain therapy for women.


1981 ◽  
Vol 90 (1) ◽  
pp. 53-58 ◽  
Author(s):  
S. M. DONOHOE ◽  
A. J. THODY ◽  
S. SHUSTER

Sexually experienced male rats were used to test the attractiveness of preputial gland odours of female rats. The male rats showed a clear preference for the preputial gland odours of hypophysectomized females given oestradiol benzoate (OB) for 3 or 8 days to those of control rats. Progesterone treatment had no effect on the attractiveness of the preputial gland odours of OB-treated hypophysectomized female rats. Administration of α-MSH for either 3 or 8 days, on the other hand, increased the attractiveness to male rats of preputial gland odours of OB-treated hypophysectomized females and the presence of progesterone produced no further change. When administered alone α-MSH had no effect on the attractiveness of the preputial gland odours. Other pituitary hormones, such as ACTH and prolactin, had no effect on the attractiveness of preputial gland odours of OB-treated hypophysectomized rats when administered for 3[unk]days. An increase in preputial gland size was only seen when OB, progesterone and α-MSH were administered together. It would appear that no relationship exists between the size of the preputial glands and their ability to attract male rats. It is concluded that, while α-MSH and progesterone may be important in controlling growth of the preputial glands, an interaction between α-MSH and oestrogen is more important for regulating the production of sex attractants by the preputial glands.


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