Incidence, growth and oestradiol-receptor levels of 7,12-dimethylbenz(a)anthracene-induced mammary tumours in rats: effects of neonatal sex steroids and oestradiol implants

1982 ◽  
Vol 95 (3) ◽  
pp. 357-368 ◽  
Author(s):  
G. Verhoeven ◽  
G. Vandoren ◽  
W. Heyns ◽  
E. R. Kühn ◽  
J. P. Janssens ◽  
...  

The effects of neonatally administered steroids on the sensitivity of the mammary gland to tumour induction by 7,12-dimethylbenz(a)anthracene was studied as a model for delayed (de)differentiating effects of steroid hormones. Immediately after birth male and female rats were gonadectomized and treated with testosterone, oestradiol or oil. Control animals were left intact. On day 45 all the gonadectomized animals and some of the control animals received an implant which delivered continuous low levels of oestradiol. The carcinogen was administered on day 55. The administration of an oestradiol implant, which increased prolactin levels in all animals, markedly reduced tumour incidence in intact female rats and increased tumour incidence in intact male rats. Neonatal administration of testosterone or oestradiol did not significantly influence tumour incidence, histopathology or oestradiol responsiveness in neonatally gonadectomized rats but tended to decrease tumour oestradiol-receptor levels. This lack of effect of neonatal steroids in gonadectomized animals suggests that the effects observed by other authors in intact rats are mediated by changes in gonadal secretions. It is concluded that the hormonal environment during and after tumour induction plays a major role in the development of 7,12-dimethylbenz(a)anthracene-induced mammary carcinomas.

1986 ◽  
Vol 61 (2) ◽  
pp. 780-784 ◽  
Author(s):  
E. H. Schlenker ◽  
M. Goldman

In this study ventilation was evaluated in 12-mo-old male and female rats who had received large doses of aspartic acid neonatally. Rats of both sexes treated with aspartic acid were obese, stunted, and exhibited hypogonadism. Although metabolic rates of the aspartic acid-treated rats were not different compared with sex-matched controls, ventilatory patterns were different. Aspartic acid-treated females breathed with a smaller tidal volume (VT), higher frequency (f), and similar minute ventilation (VE) compared with control females. This pattern is commonly observed in many patients who are obese. The aspartic acid-treated females responded to hypercapnic and hypoxic challenges by increasing f more than VT. Tissue pocket gases (PCO2 and PO2) of aspartic acid-treated females were normal. In contrast, aspartic acid-treated males hypoventilated compared with control males. Tissue pocket gas values suggested that aspartic acid-treated males were hypoxemic and hypercapnic. Moreover, the response of aspartic acid-treated males to hypercapnia was parallel to but was less than that of control male rats. The ventilatory response of aspartic acid-treated male rats to hypoxia was blunted. This study has shown that neonatal administration of aspartic acid causes a decreased ventilation and blunted response to hypoxia in adult male but not female rats.


Reproduction ◽  
2001 ◽  
pp. 915-924 ◽  
Author(s):  
L Pinilla ◽  
LC Gonzalez ◽  
F Gaytan ◽  
M Tena-Sempere ◽  
E Aguilar

Selective oestrogen receptor modulators constitute a family of drugs that are used increasingly in the management of oestrogen-associated pathology. Raloxifene is a selective oestrogen receptor modulator that is used to treat and prevent osteoporosis in post-menopausal women. The actions of raloxifene on bone, breast, uterus and serum cholesterol concentrations have been widely analysed, but very few studies have investigated the possible actions of this drug on the central nervous system. The central nervous system of the newborn rat is very sensitive to oestrogen action. In this study a series of experiments was conducted to analyse the effects of different doses of raloxifene (50, 100, 250 or 500 microg per rat per day) administered to neonatal rats on days 1-5 of age. Female rats treated with raloxifene showed decreased gonadotrophin secretion, hyperprolactinaemia, advanced vaginal opening, decreased body weight, persistent presence of cornified epithelial cells in vaginal smears, anovulation, inhibition of positive feedback between oestradiol and LH, and infertility. Male rats showed delayed balanopreputial separation, reduced body weight and hyperprolactinaemia. All these changes resemble those obtained after neonatal administration of oestradiol benzoate, thus indicating, for the first time, that raloxifene exerts an oestrogenic action on the hypothalamic-pituitary structures controlling reproductive function in rats.


1961 ◽  
Vol 36 (4) ◽  
pp. 485-497 ◽  
Author(s):  
G. P. van Rees

ABSTRACT The hypothesis that steroid sex hormones influence pituitary F. S. H. by independent actions on its production and capacity of the gland to release it has been investigated by means of incubation experiments. During incubation, rat pituitary glands released considerable amounts of F. S. H. into the medium. Inactivation of F. S. H. during incubation could not be demonstrated; once (in females) some production of F. S. H. was even observed. The amount of F. S. H. which is released into the medium is influenced by the quantity of F. S. H. stored in the hypophyses. Hypophyses from male rats pretreated with oestradiol released relatively more F. S. H. into the medium than hypophyses from control animals. On the other hand, pretreatment with testosterone caused the pituitary glands to release less F. S. H. into the medium. In agreement with these results, hypophyses from intact male rats released relatively less F. S. H. than hypophyses from intact female rats. These facts support the hypothesis that androgens depress pituitary F. S. H.-secretion by inhibiting the capacity to release it, while oestrogens, which can even promote this property of the pituitary gland, also act by directly inhibiting its production.


1979 ◽  
Vol 80 (1) ◽  
pp. 111-116 ◽  
Author(s):  
S. N. JUSTO ◽  
A. NEGRO-VILAR

A marked sexual difference in the rise of serum gonadotrophin concentrations after gonadectomy has been described in the rat. Gonadectomy in males induced a rapid rise in the concentrations of both LH and FSH within 8 to 12 h, whereas ovariectomy invoked a rapid increase in the concentration of FSH while the response by LH was delayed for several days. To determine whether these differences could be explained, at least in part, by the different steroid milieu at the time of gonadectomy, a series of experiments were performed to analyse the rise in both LH and FSH serum concentrations in control male and female rats and in male rats that had been pretreated with oestradiol-17β. Adult male rats received an s.c. implant of a silicone elastomer capsule filled with crystalline oestradiol-17 β. Controls received empty capsules. Twenty-four hours later, the oestradiol-implanted rats were castrated and control animals were sham-operated. Both LH and FSH levels remained within control levels after castration in the oestradiol-implanted rats, indicating that the oestradiol implant was preventing any rise of either gonadotrophin. On day 5 after implantation, the capsules were removed, sham-implanted animals were castrated and LH and FSH levels at 12, 24, 48 and 72 h were measured and compared with those of ovariectomized rats at similar intervals. The control male rats displayed the pattern of gonadotrophin increments normally found after castration, with both LH and FSH concentrations rising significantly by 12 h after castration and with further increments at later periods. Oestradiol-treated rats showed a female-like gonadotrophin pattern. FSH levels started to rise significantly at 24 h compared with values from intact rats and increased further at 48 and 72 h. During the first 48 h, FSH levels in both oestradiol-treated, castrated rats and female gonadectomized rats were significantly lower than in castrated animals. LH levels, on the other hand, remained low in both groups during the first 48 h, starting to rise significantly above control levels by 72 h. These results indicate that the different pattern of response to gonadectomy in rats of both sexes may be altered by changes in steroid environment and, therefore, may not be genetically predetermined.


1980 ◽  
Vol 86 (1) ◽  
pp. 79-92 ◽  
Author(s):  
W. P. HERMANS ◽  
E. C. M. VAN LEEUWEN ◽  
M. H. M. DEBETS ◽  
F. H. DE JONG

Administration of steroid-free bovine follicular fluid (bFF), containing inhibin-like activity, depressed levels of FSH measured 4 h after injection in intact adult and 35-day-old female rats, but not in younger females. Suppression of FSH was also observed in intact male rats, aged 55 days, but not in older and younger male rats. Eight hours after injection of bFF, FSH levels were depressed in 15-day-old and older immature and adult rats of both sexes. Male and female rats, gonadectomized 2 days earlier, responded similarly to bFF treatment as did the intact animals. In a second experiment it was found that the rise of FSH levels, occurring within 8 h of gonadectomy, decreased with age in male and increased with age in female rats. Steroid treatment was found to prevent the rise in FSH levels partially in 15-day-old male and completely in 25-day-old female rats, whereas treatment with bFF was fully effective in blocking the FSH rise in both immature and adult rats of both sexes. It is concluded that inhibin might be a major physiological factor in a fast-acting control of FSH concentrations from at least the age of 25 days onwards in female rats. In male rats its physiological significance might be limited to the prepubertal period, despite the fact that pituitary secretion of FSH is suppressed by exogenous inhibin-like activity at all ages studied.


1963 ◽  
Vol 43 (4) ◽  
pp. 601-608 ◽  
Author(s):  
Julian I. Kitay

ABSTRACT Administration of a depot testosterone preparation to male and female rats resulted in no change in body or pituitary weight in either sex. Pituitary corticotrophin content was unaltered in male animals but was reduced in females. Adrenal weights and adrenal RNA and DNA contents were decreased in both sexes. Plasma corticosterone concentrations were unaffected in males but were reduced in female rats after stress or corticotrophin injection. Hepatic reduction of ring A in vitro and biological half-life of corticosterone in vivo were unchanged in male animals but impaired in females. Testosterone administration to intact male rats significantly increased adrenal steroidogenesis measured in vitro. A significant decrease in steroid production was found in intact females but increased steroidogenesis was observed in adrenals from testosterone-treated oophorectomized animals. No effect was obtained following addition of testosterone directly in vitro. The data suggest that testosterone leads both to diminution of corticotrophin secretion and enhancement of adrenal steroid secretory capacity. In intact female rats, these effects are complicated by suppression of oestrogen secretion, the effects of which have been reported previously.


2006 ◽  
Vol 291 (2) ◽  
pp. R307-R314 ◽  
Author(s):  
Yaping Ji ◽  
Anne Z. Murphy ◽  
Richard J. Traub

Increasing evidence suggests there is a sex difference in opioid analgesia of pain arising from somatic tissue. However, the existence of a sex difference in visceral pain and opioid analgesia is unclear. This was examined in the colorectal distention (CRD) model of visceral pain in the current study. The visceromotor response (vmr) to noxious CRD was recorded in gonadally intact male and female rats. Subcutaneous injection of morphine dose-dependently decreased the vmr in both groups without affecting colonic compliance. However, morphine was significantly more potent in male rats than females. Because systemic morphine can act at peripheral tissue and in the central nervous system (CNS), the source of the sex difference in morphine analgesia was determined. The peripherally restricted μ-opioid receptor (MOR) antagonist naloxone methiodide dose-dependently attenuated the effects of systemic morphine. Systemic administration of the peripherally restricted MOR agonist loperamide confirmed peripherally mediated morphine analgesia and revealed greater potency in males compared with females. Spinal administration of morphine dose-dependently attenuated the vmr, but there was no sex difference. Intracerebroventricular administration of morphine also dose-dependently attenuated the vmr with significantly greater potency in male rats. The present study documents a sex difference in morphine analgesia of visceral pain that is both peripherally and supraspinally mediated.


1977 ◽  
Vol 232 (1) ◽  
pp. H12-H17 ◽  
Author(s):  
D. W. Jolly ◽  
C. Craig ◽  
T. E. Nelson

Intact male and female albino rats fed a vitamin K-deficient diet develop a plasma prothrombin-proconvertin deficiency. Male rats respond with a precipitous drop to approximately 20–30% of normal plasma levels within 2–5 days, whereas female rats respond at a slower rate. Ethynylestradiol, 5–10 mug/day, or castration, reduces the progressive decline of plasma prothrombin-proconvertin seen in nonsupplemented intact male rats. The response of castrate females differs little from the response of intact females. Ethynylestradiol, 5–10 mug/day, affects both castrate males and females similarly, limiting the prothrombin-proconvertin decrease to about 13% below control value after 14 days. Intestinal absorption of vitamin K1 measured in the thoracic duct lymph of pentobarbital-anesthetized castrate male and female rats was shown to increase significantly after estrogen treatment. Estrogen-treated castrate male and female rats absorbed 25.8 mug and 11.8 mug vitamin K1, respectively. Nontreated control castrate male and female rats absorbed 0.0 mug and 1.2 mug, respectively, during a 240-min collection period. Use of radioactive vitamin K1 in similar experiments confirmed these results. Estrogen-treated castrate males absorbed vitamin K1 at the rate of 30-40 mug/g lymph whereas nontreated control males absorbed only about 6 mug/g lymph.


2006 ◽  
Vol 291 (2) ◽  
pp. R343-R348 ◽  
Author(s):  
Natasha M. Flake ◽  
Tracey O. Hermanstyne ◽  
Michael S. Gold

The present study was designed to test the hypothesis that estrogen exacerbates inflammation of the temporomandibular joint (TMJ). Evans blue dye was used to quantify plasma extravasation (PE) around the rat TMJ. In an initial set of experiments, TMJ PE was compared in naïve intact male and female rats, as well as in both groups after complete Freund’s adjuvant (CFA)-induced inflammation of the TMJ. In contrast to our hypothesis, TMJ PE was significantly greater in both naïve and CFA-inflamed male rats than in females. To determine whether these differences were due to gonadal hormones, four additional groups of rats were studied: gonadectomized (Gx) males and females, Gx males with chronic testosterone (T) replacement, and Gx females with chronic estrogen (E) replacement. The sex difference in baseline TMJ PE appeared to reflect the actions of T. However, in the presence of TMJ inflammation, T augmented TMJ PE in males, while E attenuated TMJ PE in females. Changes in PE were also assessed in the contralateral TMJ. Results from this analysis indicated that there is a transient contralateral increase in TMJ PE in females but not males. Given that there is an inverse relationship between PE and joint damage, our results suggest that testosterone may mitigate, but estrogen may exacerbate, TMJ damage, particularly in the presence of overt inflammation. Importantly, our results may help explain both the higher prevalence and severity of temporomandibular disorder pain in females than males.


1980 ◽  
Vol 85 (3) ◽  
pp. 351-358 ◽  
Author(s):  
F. T. DIONNE ◽  
J. Y. DUBÉ ◽  
G. FRENETTE ◽  
R. R. TREMBLAY

Hormonal regulation of cytosolic oestradiol-binding sites in the levator ani bulbocavernosus (LA/BC) muscles of male rats and in thigh muscles from male and female rats was investigated. Twenty-four hours after gonadectomy and/or adrenalectomy, the number of unoccupied oestradiol-binding sites was significantly increased in cytosols prepared from LA/BC muscles while these treatments had no effect on thigh muscles from male rats. Only a combination of both treatments led to a significant increase of oestradiol-binding sites in cytosols prepared from the thigh muscles of female rats when compared with those of intact rats at dioestrus. The number of oestradiol-binding sites in the thigh muscles of female rats was found to vary during the oestrous cycle with values significantly lower at pro-oestrus than at dioestrus. The increase in oestradiol-binding sites observed in cytosols prepared from muscles of adrenalectomized or gonadectomized plus adrenalectomized rats was prevented by an injection of corticosterone (3 mg, s.c.) at the time of surgery. Twenty-one days after gonad and/or adrenal ablation, the mean concentration of oestradiol-binding sites in the three tissues under study was higher than in these tissues from intact rats, and in some groups the levels of oestradiol-binding sites were significantly higher than they had been 24 h after the same surgical treatments. Muscles from male rats hypophysectomized for 28 days possessed levels of oestradiol-binding sites equivalent to male rats deprived of steroid hormones for 21 days. Dexamethasone treatment of male rats (100 μg/day for 14 days) led to a progressive decrease of oestradiol-binding sites of LA/BC and thigh muscles. This study has shown that adrenal and gonadal hormones exert both short- and long-acting repressive effects on the oestradiol-binding capacity of rat muscles.


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