ANDROGENIC PROPERTIES AND ADRENAL DEPRESSANT ACTIVITY OF MEGESTROL ACETATE OBSERVED IN CASTRATED MALE RATS

1975 ◽  
Vol 78 (2) ◽  
pp. 316-324 ◽  
Author(s):  
Lars-Eric Tisell ◽  
Håkan Salander

ABSTRACT Megestrol acetate (17α-acetoxy-6-dehydro-6-methylprogesterone), a synthetic steroid with high progestational activity, is used in oral contraceptives but also in the treatment of prostatic diseases in man. To investigate whether megestrol acetate has any androgenic properties the growth of the ventral and dorsolateral prostate, the coagulating glands and the seminal vesicles was studied morphologically in castrated rats treated with megestrol acetate and in non-treated castrated rats. The effect of megestrol acetate on the body weight, the levator ani muscle and the adrenals was also studied. Megestrol acetate was administered in daily doses of 0.02 mg, 0.2 mg, 2.0 mg or 20.0 mg for a period of 21 days. Megestrol acetate in the two higher doses retarded growth and gave a low weight for the levator ani muscle at autopsy indicating an anti-anabolic or catabolic action of megestrol acetate in high doses. Megestrol acetate in daily doses of 0.2, 2.0 and 20.0 mg caused an involution of the adrenal glands. After the two higher doses the weight of the adrenals amounted to only about a third of that of the untreated rats. Megestrol acetate in the lower doses had no demonstrable effect on the growth of the accessory reproductive glands. After the two higher doses of megestrol acetate some growth of the dorsal part of the dorsolateral prostate and of the coagulating glands was observed. Only the seminal vesicles exhibited complete morphological criteria of an androgenic stimulation and then only after the largest dose of megestrol acetate. The investigation shows that megestrol acetate has weak androgenic properties which are apparent at a dose per kg body weight approximately 200 times greater than that used in the treatment of prostatic diseases in man.

1967 ◽  
Vol 56 (2) ◽  
pp. 221-224 ◽  
Author(s):  
A. P. Baker ◽  
F. Bergman ◽  
B. Josefsson ◽  
K. G. Paul

ABSTRACT Castrated, adult male rats were given a long-acting androgen in doses that caused a rapid growth of the anterior prostate lobes, the seminal vesicles, and the levator ani muscle. There was no decrease in the number of mast cells, and no increase in the number of eosinophils.


1966 ◽  
Vol 51 (2) ◽  
pp. 315-320 ◽  
Author(s):  
C. M. Goodall ◽  
J. B. Gavin

ABSTRACT Male rats were hypophysectomized at four weeks of age, rested for four weeks, and then were fed a thyroid digest in their drinking water continuously for up to seventy weeks. The digest treatment supplied the equivalent of 1.25μg L-thyroxine per 100 g rat per day approximately. From the body weight curves and radiographic measurements of the skull and mandibles, it was shown that contrary to some previous reports in the literature there was no statistically significant change in the indices of growth or body mass when compared with controls receiving no thyroid treatment. It is suggested that data previously reported by others, indicating a stimulation of growth in hypophysectomized rats by thyroid hormones, may have been derived from animals having minute but still effective pituitary remnants, and somewhat more stringent morphological criteria of hypophysectomy are proposed.


1969 ◽  
Vol 62 (4) ◽  
pp. 694-710 ◽  
Author(s):  
Lars-Eric Tisell ◽  
Lennart Angervall

ABSTRACT The growth of the ventral and the dorsolateral prostate, the coagulating glands, seminal vesicles and levator ani muscle was studied in castrated male rats after fifteen days of daily injections with ACTH or insulin alone, or in combination. ACTH was given in a dose of 8 IU daily. Insulin was administered in increasing daily doses, i. e. regular insulin up to 8 IU and protamine zinc insulin up to 10 IU. After ACTH treatment there were variable histological signs of stimulation of the dorsolateral prostate, while the other accessory reproductive organs showed no response. Regular insulin produced no quantitative or morphological changes in the accessory reproductive organs, and no morphological signs of increased secretion of the adrenal steroids. Administration of ACTH and regular insulin in combination stimulated the growth of all the accessory reproductive organs. Protamine zinc insulin produced prolonged hypoglycaemia and morphological signs of increase secretion of adrenal steroids, thus the adrenals became enlarged and the thymus atrophic. Protamine zinc insulin stimulated growth of all the accessory reproductive organs, a stimulation which was further accentuated after combination with ACTH. Possible mechanisms for the action of insulin on the male accessory reproductive organs are discussed. The varying response of the different parts of the prostate and the seminal vesicles emphasizes the importance of the simultaneous examination of these organs.


1963 ◽  
Vol 42 (4) ◽  
pp. 601-614 ◽  
Author(s):  
K. Ahrén ◽  
A. Arvill ◽  
Ä. Hjalmarson

ABSTRACT Methandrostenolone (17β-hydroxy-17α-methyl-androsta-1,4-dien-3-one) was injected in 4 dose-levels (0.05, 0.5, 2.5 and 5.0 mg daily for 28 days) into castrated male rats, and the response of the mammary glands, the seminal vesicles and the levator ani muscle studied. One dose-level (2.5 mg daily for 28 days) was injected into castrated female rats, and the response of the mammary glands, the vagina and the uterus studied. The main results were as follows: The 0.05 mg dose did not stimulate the seminal vesicles but produced a slight weight increase of the levator ani muscle. The 0.5 mg dose had only a minimal effect on the seminal vesicles but had a much more pronounced effect on the levator ani muscle. The 2 higher doses, however, markedly stimulated both the seminal vesicles and the levator ani muscle. In the mammary glands methandrostenolone produced not only lobule-alveolar development, as do most other androgens, but in addition induced growth and development of the mammary duct system, as found with oestrogenic compounds. The lobule-alveolar development, found after treatment with the various dose-levels of methandrostenolone, quantitatively, more closely followed the growth of the levator ani muscle than the development of the seminal vesicles. In the castrated female rats methandrostenolone stimulated vaginal opening, brought about slight cornification of the vaginal epithelium and caused a marked weight increase of the uterus. These effects cannot be explained solely on the basis of the androgenic activity of this compound, but seem to indicate that methandrostenolone has an oestrogenic activity when injected into castrated rats.


1964 ◽  
Vol 47 (2) ◽  
pp. 200-208 ◽  
Author(s):  
Fred A. Kind ◽  
Manuel Maqueo ◽  
A. Folch Pi

ABSTRACT Groups of five day old rats were injected with 120 or 240 μg of oestradiol benzoate. When examined at the age of fifty days, the animal presented atrophied testes and marked decreases in the weights of ventral prostate, seminal vesicles and levator ani muscle. Treatment with pregnant mare's serum or with testosterone propionate given from day 20 through day 50 fully restored the gonadal activity. The dose of PMS needed to restore spermatogenesis was 10 IU which was given every third day. Testosterone propionate, 1 mg, given daily was equally effective.


1962 ◽  
Vol 39 (4) ◽  
pp. 584-598 ◽  
Author(s):  
K. Ahrén ◽  
A. Arvill ◽  
Å. Hjalmarson

ABSTRACT The response of the seminal vesicles, the levator ani muscle and the mammary glands to testosteronephenylpropionate (TPP) and 19-nortestosteronephenylpropionate (19-norTPP) was studied in castrated male rats. The development of these structures was compared with that found in male rats with intact testes. The main results were as follows: 1) Daily injections of 0.01 mg of TPP produced slight weight increase in the seminal vesicles and levator ani muscle and stimulated a slight but obvious lobule-alveolar development in the mammary glands. The same dose of 19-norTPP produced only a minimal weight increase in the seminal vesicles but produced an obvious development of the levator ani muscle and the mammary glands. 2) Daily injections of 0.05 mg of TPP caused a marked weight increase in the seminal vesicles and levator ani muscle and produced a marked lobule-alveolar development in the mammary glands. The same dose of 19-norTPP produced only a slight weight increase in the seminal vesicles but brought about a marked development of the levator ani muscle and the mammary glands. 3) Daily injections of 0.5 mg of 19-norTPP caused a marked development of the seminal vesicles comparable to that found in rats with intact testes. The levator ani muscle and the mammary glands after this treatment were, however, much more stimulated than in rats with intact testes. These results indicate 1) that the ratio between the effects of these compounds on the seminal vesicles and on the Ievator ani muscle depends on the dose-level and 2) that the development of the mammary glands is correlated more to the growth of the Ievator ani muscle than to the development of the seminal vesicles.


2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Tai-Yuan Chuang ◽  
Chia-Ying Lien ◽  
Chih-Hsiang Hsu ◽  
Chen-Wen Lu ◽  
Chung-Hsin Wu

Hypothyroidism frequently causes cardiopulmonary dysfunction, such as heart failure and respiratory and metabolic deficiencies. This study investigated the effects of Chinese herbal formula B307 on thyroidectomy-induced cardiopulmonary exercise dysfunction in rats. Twenty male rats were equally divided into four groups: negative control with sham treatment, positive control with oral B307 treatment only, thyroidectomy treatment only, and thyroidectomy with B307 posttreatment groups. The feeding dose of B307 was 50 mg/kg per day for 14 days. We examined and then compared the thyroid-stimulating hormone (TSH), free triiodothyronine (T3), free thyroxine (T4), and reactive oxygen species (ROS) from the blood of these four groups. Also, we compared the body weight, neck subcutaneous blood flow, cardiac ejection function, cardiopulmonary exercise function of oxygen consumption (VO2), carbon dioxide production (VCO2), and respiratory quotient (RQ = VCO2/VO2) among the four groups. Our results indicated that thyroidectomized rats had significantly decreased body weight, neck subcutaneous blood flow, cardiac ejection function, serum T3 and T4, and VO2 and VCO2, but had significantly increased ROS and TSH levels and RQ values compared with sham rats (P<0.01–0.05). In addition, thyroidectomized rats receiving oral B307 treatment had significantly increased body weight, neck subcutaneous blood flow, cardiac ejection function, and VO2, but significantly decreased ROS and TSH levels and VCO2 and RQ values compared with thyroidectomized rats (P<0.01–0.05). We suggest that the B307 could be a protective and beneficial alternative treatment for thyroidectomy-induced cardiopulmonary exercise dysfunction.


2020 ◽  
Vol 99 (11) ◽  
pp. 1276-1279
Author(s):  
Valery N. Rakitskii ◽  
Tatiana M. Epishina ◽  
Elena G. Chkhvirkiya

Introduction. Historically, pesticides are evaluated more strictly from a medical point of view than other chemicals. Since their features, such as deliberate introduction into the environment, the possibility of contact with them by large masses of the population, and the high biological activity determine their potential danger to humans. Purpose of research - study of the biological effect of a technical product derived from triazoles when it is repeatedly ingested orally in mammals (rats), establishment of inactive and active doses, justification of the permissible daily dose (DSD) for humans. Material and methods. In acute experiments, white rats were used, including 6 animals in the group. Tested dose: 500-4000 mg/kg of body weight. A chronic (12 months) experiment was performed on 80 male rats with a bodyweight of 180-190 g at the beginning of the study. Tested doses: 5.0; 16.0 and 55.0 mg/kg of body weight (1 control and 3 experimental animals, 20 individuals each). In the dynamics of the experiment, we observed the condition and behavior of animals, water, and food consumption, recorded the timing of death, changes in body weight, physiological, biochemical, and hematological indices. Results. Indices of the acute oral toxicity on the studied product LD50 male rats were 2250 ± 483 mg/kg body weight. The dose of 5.0 mg / kg of body weight was not found to cause significant changes in all studied indices. The doses of 16.0 and 55.0 mg/kg of body weight had a polytropic effect on the body in experimental animals. Discussion. The studied product for the acute oral toxicity refers to low-hazard compounds, the doses of 16.0 and 55.0 mg/kg of body weight has a polytropic effect on the mammalian body, causing changes in carbohydrate, lipid, and lipoprotein metabolism in the body of rats - was accepted as acting. The dose of 5.0 mg / kg of body weight, when administered in rats, there are no changes in all the studied parameters throughout the experiment, is accepted as invalid. Based on the inactive dose-5.0 mg/kg of body weight and taking into account the reserve factor of 100, we have scientifically justified DSD for a person at the level of 0.05 mg/kg. Summary. The conducted sanitary and Toxicological studies indicate the need to assess the toxicity of new technical products to the mammalian body, to increase the reliability of the developed hygiene standards in environmental objects and food products.


F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 130
Author(s):  
Novita Sari Harahap ◽  
Aznan Lelo ◽  
Ambrosius Purba ◽  
Awaluddin Sibuea ◽  
Rina Amelia ◽  
...  

Background: Oxidative stress from exercise can contribute to damaging cells, increasing heat shock protein 70 (HSP70) and suppressing the immune system in the body. This research aimed to determine the antioxidant potential of red-fleshed pitaya extract on HSP70 and cortisol expression in rats which were subjected to strenuous exercise. Methods: The subjects of this research were 32 Sprague Dawley male rats, aged 3 months, with an average weight of 200 g. Red-fleshed pitaya extract was obtained from methanol extraction process; a maceration technique was performed and the extract was concentrated using an air-drying method. Rats were randomly divided into four groups. Group 1 were subjected to strenuous exercise and treated with distilled water only; while Groups 2, 3 and 4 were subjected to strenuous exercise and treated with 100 mg/kg body weight, 200 mg/kg body weight and 300 mg/kg body weight of red-fleshed pitaya extract, respectively. Strenuous exercises in rats was performed by intense swimming of 20 min/day, 3 days a week for 3 weeks. HSP70 expression and cortisol were measured with Enzyme-Linked Immune Sorbent Assay (ELISA) method. Results: There was a significant reduction of HSP70 (p=0.000) and cortisol expression (p=0.000) between the groups. Also, there was a significant difference in the average decreasing of HSP70 expression between group 4 and either groups 1 or 2 (p=0.000). However, a significant difference between groups 4 and 3 was not observed (p=0.813). Lastly, a significant difference was found in the average decrease of cortisol expression between groups 4 and 1 (p=0.000), 2 (p=0.000), and 3 (p=0.000) respectively. Conclusion: Red-fleshed pitaya is potential to be utilized as antioxidant to decrease the HSP70 and cortisol expression.


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