THE »EARLY-ANDROGEN« SYNDROME; DIFFERENCES IN RESPONSE TO PRE-NATAL AND POST-NATAL ADMINISTRATION OF VARIOUS DOSES OF TESTOSTERONE PROPIONATE IN FEMALE AND MALE RATS

1964 ◽  
Vol 47 (1) ◽  
pp. 37-50 ◽  
Author(s):  
H. E. Swanson ◽  
J. J. van der Werff ten Bosch
Keyword(s):  
Critical Period ◽  
Ovarian Function ◽  
Testosterone Propionate ◽  
Single Injection ◽  
Male Rats ◽  
Male Rat ◽  
High Dose ◽  
Corpora Lutea ◽  
Female Rat ◽  
Time Of Administration

ABSTRACT The interaction between dose and time of administration of testosterone propionate (TP) on the development of sexual function was studied by giving a single dose of 5, 10, 50 or 500 μg TP to young rats of both sexes on the day of birth (day 1) or on day 2, 4 or 5. The effectiveness of androgen administration before birth was studied by giving a single injection of 2500 μg TP to pregnant rats on day 19 to 22 after conception. Pre-natal administration had no effect on the function of the ovaries of female offspring, although the dose was sufficient to cause masculinization of the external genitalia. The weight of the testes and accessories of the male offspring were not affected. The effects of post-natal TP administration on ovarian function varied with the dose and with the time of administration. Threshold doses (5 and 10 μg) were more effective the earlier they were given after birth. With these small doses, most of the rats had normal luteinized ovaries at 10 weeks and were able to bear and suckle normal litters. Some time later ovulations ceased so that at 21 weeks they were no longer fertile; at 27 weeks there were no more corpora lutea in the ovaries. In males, a dose of 50 μg of TP or more resulted in permanently reduced weight of testes, seminal vesicles and prostate. The earlier the treatment, the more marked was the depression of weight. From these results and others reported in the literature the following deductions can be made: (1) the critical period of brain sensitivity to physiological amounts of androgen probably lies between days 4 and 6 (day of birth counted as day 1); (2) a rough estimate of the amount of androgen secreted by the newborn male rat during the critical period would seem to be the equivalent of a single injection of 5–50 μg TP; (3) after the physiological critical period has elapsed a female rat can still be »masculinized« if a high dose of TP is given, up to a period of between 10–20 days after birth.

Inductive influence of testosterone upon central sexual maturation in the rat

Development ◽  
1967 ◽  
Vol 17 (1) ◽  
pp. 171-175
Author(s):  
W. N. Adams Smith ◽  
M. T. Peng
Keyword(s):  
Corpus Luteum ◽  
Sex Hormones ◽  
Adult Male ◽  
Sexual Maturation ◽  
Male Genitalia ◽  
Testosterone Propionate ◽  
Single Injection ◽  
Male Rats ◽  
Corpora Lutea

The influence of the testis and of testosterone upon the development of the male genitalia has been extensively investigated and a number of reviews of this work have been published (Jost, 1960; Burns, 1961). However, Witschi (1957) has stressed the need to distinguish between adult sex hormones, such as testosterone, and the secretions of the immature gonad. The formation of corpora lutea in the ovaries transplanted to adult male rats which had been castrated at birth, and the absence of corpus luteum formation in ovaries transplanted to male hosts bearing transplanted testes in the neck from birth, was reported by Pfeiffer in 1936. Similar observations have been reported by Yazaki (1960) and Harris (1964). A single injection of testosterone propionate has been found to lead to permanent sterility and a loss of corpus luteum formation in the ovaries of mice (Barraclough & Leathern, 1954) and rats (Barraclough, 1961).

EXPERIMENTAL EVALUATION OF DIURETICS IN THE RAT

1956 ◽  
Vol 34 (1) ◽  
pp. 903-911
Author(s):  
J. D. McColl ◽  
J. M. Parker ◽  
J. K.W. Ferguson
Keyword(s):  
Carbonic Anhydrase ◽  
Dose Range ◽  
Carbonic Anhydrase Inhibitor ◽  
Female Rats ◽  
Male Rats ◽  
Male Rat ◽  
High Dose ◽  
Female Rat ◽  
Inhibitor Type ◽  
Almost All

The diuretic response of the male and the female rat to aminophylline has been studied when these animals were pretreated with various concentrations of sodium chloride solution. A linear log dose – response curve was obtained over the dose range employed with male rats pretreated with 0.45% and 2% saline. Male rats exhibited a diuresis with 4% saline which was not increased by aminophylline. Female rats showed diuresis but the responses were more variable for almost all combinations of electrolyte load and xanthine dose. When they were pretreated with 0.45% and 2% saline, aminophylline caused some additional production of urine but this was much less regular than that observed with males. The variation in response to aminophylline after 4% saline was very marked but the trend suggested that the xanthine had a diuretic effect at the high dose. The diuretic responses to a xanthine, a mercurial, and a carbonic anhydrase inhibitor type of diuretic were compared in the male rat. Peak responses were smallest after the mercurial diuretic and greatest with the carbonic anhydrase inhibitor.

EXPERIMENTAL EVALUATION OF DIURETICS IN THE RAT

1956 ◽  
Vol 34 (5) ◽  
pp. 903-911 ◽  
Author(s):  
J. D. McColl ◽  
J. M. Parker ◽  
J. K.W. Ferguson
Keyword(s):  
Carbonic Anhydrase ◽  
Dose Range ◽  
Carbonic Anhydrase Inhibitor ◽  
Female Rats ◽  
Male Rats ◽  
Male Rat ◽  
High Dose ◽  
Female Rat ◽  
Inhibitor Type ◽  
Almost All

The diuretic response of the male and the female rat to aminophylline has been studied when these animals were pretreated with various concentrations of sodium chloride solution. A linear log dose – response curve was obtained over the dose range employed with male rats pretreated with 0.45% and 2% saline. Male rats exhibited a diuresis with 4% saline which was not increased by aminophylline. Female rats showed diuresis but the responses were more variable for almost all combinations of electrolyte load and xanthine dose. When they were pretreated with 0.45% and 2% saline, aminophylline caused some additional production of urine but this was much less regular than that observed with males. The variation in response to aminophylline after 4% saline was very marked but the trend suggested that the xanthine had a diuretic effect at the high dose. The diuretic responses to a xanthine, a mercurial, and a carbonic anhydrase inhibitor type of diuretic were compared in the male rat. Peak responses were smallest after the mercurial diuretic and greatest with the carbonic anhydrase inhibitor.

THE EFFECTS OF ORCHIDECTOMY AND TESTOSTERONE PROPIONATE INJECTION ON PEPTIDASE ACTIVITY IN THE MALE RAT HYPOTHALAMUS

1973 ◽  
Vol 72 (1) ◽  
pp. 1-8 ◽  
Author(s):  
E. C. Griffiths ◽  
K. C. Hooper
Keyword(s):  
Luteinizing Hormone ◽  
Testosterone Propionate ◽  
Female Rats ◽  
Male Rats ◽  
Male Rat ◽  
Peptidase Activity ◽  
Female Rat ◽  
Similar Relationship ◽  
Testosterone Treatment ◽  
Rat Hypothalamus

ABSTRACT It has previously been shown that the activity of certain peptidases in the female rat hypothalamus is related to the release of luteinizing hormone releasing factor from the tissue (Griffiths & Hooper 1972a). The activity of these enzymes was investigated after orchidectomy and testosterone propionate injection to determine if a similar relationship exists in male rats. The depression in supernatant activity following orchidectomy and the elevation after testosterone treatment are interpreted as confirming this, and it is proposed that alterations in peptidase activity may be used as an index of gonadotrophin release in male as well as in female rats.

EXPERIMENTAL STUDIES ON THE REGULATION OF CORPUS LUTEUM FUNCTION IN CASTRATED MALE RATS BEARING A TRANSPLANTED OVARY

1963 ◽  
Vol 43 (2) ◽  
pp. 246-254 ◽  
Author(s):  
G. H. Zeilmaker
Keyword(s):  
Pituitary Gland ◽  
Corpus Luteum ◽  
Functional Activity ◽  
Experimental Studies ◽  
Female Rats ◽  
Male Rats ◽  
Male Rat ◽  
Corpora Lutea ◽  
Female Rat ◽  
Progesterone Production

ABSTRACT The functional activity of artificially induced corpora lutea in isologous ovaries transplanted into castrated male rats has been studied. Criteria for progesterone production were the morphology of vaginal transplants and the distribution of sudanophilic material in the corpus luteum cells. It was found that spontaneous functional activity of the corpora lutea did not occur in short-term experiments. Progesterone production was observed, however, in animals also bearing an isotransplanted (either male or female) pituitary gland, and in animals which received daily injections of reserpine. It is suggested that the normal influence of the central nervous system on the secretion of luteotrophic hormone is inhibitory in male as well as in female animals. Some aspects of the induction and maintenance of luteal function in castrated male rats bearing a transplanted ovary have been studied and compared with similar phenomena in the female rat. A real pseudopregnancy, i. e. maintained by the pituitary in situ during a defined period, as can be observed in female rats, could not be induced in these animals. In animals also bearing an isografted pituitary gland, luteolysis was not observed in experiments lasting up to 45 days. It is suggested that these findings may be correlated with the way in which the luteinizing hormone is secreted in the male rat.

The ovary and sexual maturation of the brain

Development ◽  
1967 ◽  
Vol 17 (1) ◽  
pp. 1-10
Author(s):  
W. N. Adams Smith
Keyword(s):  
Corpus Luteum ◽  
Direct Effect ◽  
Sexual Maturation ◽  
Ovarian Function ◽  
Testosterone Propionate ◽  
Single Injection ◽  
Female Rats ◽  
Corpora Lutea ◽  
Litter Mate ◽  
The Brain

Pfeiffer (1935, 1936) reported the induction of constant oestrus in female rats following the transplantation of testes from litter-mate males just after birth and noted that the ovaries of these animals did not contain corpora lutea. These changes remained after removal of the testis transplants. The same effects were obtained by Bradbury (1941) following the administration of multiple doses of testosterone propionate. Barraclough & Leathern (1954) found that a single injection of 1 mg of testosterone propionate at 5 days of age led to permanent sterility in female mice, with no corpus luteum formation in their ovaries. Similar results were obtained in rats by Barraclough (1961) with the administration of a single injection of 1·25 mg of testosterone propionate. This permanent change in ovarian function does not appear to be a direct effect upon the ovary (Bradbury, 1941).

THE »EARLY-ANDROGEN« SYNDROME; ITS DEVELOPMENT AND THE RESPONSE TO HEMI-SPAYING

1964 ◽  
Vol 45 (1) ◽  
pp. 1-12 ◽  
Author(s):  
H. E. Swanson ◽  
J. J. van der Werff ten Bosch
Keyword(s):  
Sexual Maturity ◽  
Compensatory Growth ◽  
Testosterone Propionate ◽  
Single Injection ◽  
Weight Increase ◽  
Corpora Lutea ◽  
Transition Stage ◽  
Adult Females

ABSTRACT The »early-androgen« syndrome in the rat – i. e. anovulatory ovaries in adult females after a single injection of testosterone propionate (TP) within a week of birth – may not become apparent until some time after the attainment of sexual maturity. Large doses (50 or 100 μg) of TP were effective earlier than lower doses (5 or 10 μg). Rats which received 5 μg TP were ovulating at 10 weeks of age, mated but were infertile at 13 weeks of age, and were anovulatory at 21 weeks. In rats between 10 and 13 weeks old there was a marked fall in the number of corpora lutea in the ovaries of animals which had been given 5 μg TP. Hemi-spaying was followed by compensatory growth of the remaining ovary which consisted of corpora lutea in ovulating, and of follicles in anovulatory rats; little or no compensatory weight increase occurred in animals which seemed to be in the transition stage from the ovulatory to the anovulatory condition.

scholarly journals A rodent model of human dose-equivalent progestin-only implantable contraception

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Heather C. M. Allaway ◽  
Roger A. Pierson ◽  
Jesse Invik ◽  
Susan A. Bloomfield
Keyword(s):  
Repeated Measures ◽  
Ovarian Function ◽  
Virgin Female ◽  
Rodent Model ◽  
High Dose ◽  
Corpora Lutea ◽  
Average Dose ◽  
Estrus Cycle ◽  
Human Dose ◽  
Dose Dependent

Abstract Background Long-acting, reversible contraceptives (LARC; progestin only) are an increasingly common hormonal contraceptive choice in reproductive aged women looking to suppress ovarian function and menstrual cyclicity. The overall objective was to develop and validate a rodent model of implanted etonogestrel (ENG) LARC, at body size equivalent doses to the average dose received by women during each of the first 3 years of ENG subdermal rod LARC use. Methods Intact, virgin, female Sprague-Dawley rats (16-wk-old) were randomized to 1 of 4 groups (n = 8/group) of ENG LARC (high-0.30μg/d, medium-0.17μg/d, low-0.09μg/d, placebo-0.00μg/d) via a slow-release pellet implanted subcutaneously. Animals were monitored for 21 days before and 29 days following pellet implantation using vaginal smears, ultrasound biomicroscopy (UBM), saphenous blood draws, food consumption, and body weights. Data were analyzed by chi-square, non-parametric, univariate, and repeated measures 2-way ANOVA. Results Prior to pellet implantation there was no difference in time spent in estrus cycle phases among the treatment groups (p > 0.30). Following pellet implantation there was a dose-dependent impact on the time spent in diestrus and estrus (p < 0.05), with the high dose group spending more days in diestrus and fewer days in estrus. Prior to pellet insertion there was not an association between treatment group and estrus cycle classification (p = 0.57) but following pellet implantation there was a dose-dependent association with cycle classification (p < 0.02). Measurements from the UBM (ovarian volume, follicle count, corpora lutea count) indicate an alteration of ovarian function following pellet implantation. Conclusion Assessment of estrus cyclicity indicated a dose-response relationship in the shift to a larger number of acyclic rats and longer in duration spent in the diestrus phase. Therefore, each dose in this model mimics some of the changes observed in the ovaries of women using ENG LARC and provides an opportunity for investigating the impacts on non-reproductive tissues in the future.

Certain aspects of the host-parasite relationship ofNematospiroides dubius(Baylis). II. The effect of sex on experimental infections in the rat (an abnormal host)

Parasitology ◽  
1961 ◽  
Vol 51 (3-4) ◽  
pp. 499-510 ◽  
Author(s):  
Colin Dobson
Keyword(s):  
Male Rats ◽  
Male Rat ◽  
Normal Male ◽  
Female Rat ◽  
Castrate Male ◽  
Parasite Relationship ◽  
Nematospiroides Dubius ◽  
Resistance To Infection ◽  
Host Parasite ◽  
The Relationship

1. The male rat is more susceptible to infections ofNematospiroides dubiusthan the female. As the rat grows older the resistance of the female rat to infection increases at a greater rate than that of the male.2. The course of the infection is modified by the sex of the host.3. More larvae penetrated the intestinal mucosa to encyst in the male than in the female. More larvae, however, formed cysts in the female than in the male rat by the fifth day.4. The male harboured more adult worms than the female rat, although this difference was not significant in the immature animals.5. The sex resistance of the rat toN. dubiusinfections was removed by bilateral gonadectomy. Castration decreased the susceptibility of the male rat, while spaying increased it in the female compared with the susceptibility in the respective normal hosts.6. Subsequent replacement of the homologous sex hormone in the gonadectomized rat restores the sex resistance, and may even increase it (particularly in the immature animals). Oestradiol increased the resistance of the spayed female rat, while testosterone increased the susceptibility of the castrate male rat to infection.7. Oestradiol implanted in castrate male rats increased the resistance of these hosts to a greater level than was shown in the normal male rat.8. The rat shows a marked age resistance over which the sex resistance is superimposed.9. The relationship between the sex of the host and its resistance to infection is discussed.This work was done during the tenure of a Department of Scientific and Industrial Research Studentship. My thanks are due to Dr E. T. B. Francis for his helpful and critical supervision and to Professor I. Chester Jones, in whose department the work was done, for the facilities he provided.

scholarly journals Increased bioactivation of dihaloalkanes in rat liver due to induction of class Theta glutathione S-transferase T1-1

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 ◽  
...  
Keyword(s):  
Western Blotting ◽  
Rat Liver ◽  
Female Rats ◽  
Male Rats ◽  
Male Rat ◽  
Female Rat ◽  
Glutathione S Transferase ◽  
Chemopreventive Agents ◽  
Cytoplasmic Staining ◽  
Potent Inducer

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.

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