EFFECT OF ANDROGENIC AND ANABOLIC COMPOUNDS ON PSEUDOCHOLINESTERASE ACTIVITY IN THE LIVER AND SERUM OF THE RAT

1965 ◽  
Vol 50 (3) ◽  
pp. 391-402 ◽  
Author(s):  
R. S. Leeuwin

ABSTRACT Immature male and female rats have a similar basal level of pseudocholinesterase activity in the liver and serum. In male rats pseudocholinesterase activity declines sharply with the onset of sexual maturity, between the fourth and the fifth week, after which it remains more or less constant. In female rats, also coinciding with the onset of sexual development, the activity starts to rise between five and six weeks and then increases gradually up to twenty weeks. Castration of male rats results in an increase of the enzyme activity to the basal level, whereas subsequent injection of testosterone-propionate brings about a fall to the level found in adult male rats. Three androgenic/anabolic steroids were compared for their effects on pseudocholinesterase activities in liver and serum of male castrates, viz. testosterone-propionate, testosterone-phenyl-propionate and nor-testosterone-phenyl-propionate, the latter known to possess a relatively high anabolic potency. This was confirmed in our experiments by direct protein determinations in liver and serum and by levator ani muscle/seminal vesicle ratios. At a dose of 1 mg daily for ten days, the former two substances had a similar considerable effect on pseudocholinesterase activity, whereas the effect of the nor-derivative was much smaller. A response similar to that of one milligram of testosterone-propionate was only obtained with 4 mg of the nor-derivative. At that dose level the androgenic effect of the nor-derivative on the seminal vesicles is somewhat less than that of 1 mg testosterone-propionate daily. It is concluded that the cholinesterase activity lowering effect of the compounds investigated is correlated with their androgenic rather than with their anabolic potencies.

1960 ◽  
Vol XXXV (III) ◽  
pp. 405-412 ◽  
Author(s):  
J. de Visser ◽  
G. A. Overbeek

ABSTRACT 1. The pharmacological properties of nandrolone decanoate (= caprinate), by abbreviation nor-A. D., have been studied. 2. Nor-A. D. has a marked, long-lasting effect on the levator ani muscle of the castrated rat, but it has little activity on the seminal vesicles and prostate. 3. Nor-A. D. displays only weak gonad inhibiting properties in male and female rats. 4. The anti-oestrogenic activity is low. 5. At high dose levels the anabolic activity becomes maximal and the other effects become evident. The same can be expected to occur if injections are administered with too great a frequency. 6. Chronic toxicity studies in rats and dogs demonstrate its lack of toxicity.


1970 ◽  
Vol 64 (3) ◽  
pp. 531-540 ◽  
Author(s):  
R. S. Leeuwin ◽  
E. Th. Groenewoud

ABSTRACT Testosterone (T), testosterone-propionate (TP), testosterone-phenyl-propionate (TPP), nandrolone (N) (19-nor-testosterone) and nandrolone-phenyl-propionate (NPP) were compared for their effects on the pseudocholinesterase activities in the liver and serum of castrated male rats. In addition changes in the weight of the seminal vesicle and the levator ani muscle were studied. After daily administration of 1 mg of the hormones for ten days, T and TPP showed a more marked depression of the pseudocholinesterase activity and seminal vesicle than the corresponding nor-derivatives. TP and TPP have approximately similar effects, exceeding those of T. On the levator ani N and NPP were more effective than T and TPP. At identical total doses, administration of all hormones with intervals of more than one day, produced less depression of the pseudocholinesterase activity and less seminal vesicle growth than daily administration. The effects on the levator ani were less influenced by varying intervals. At an interval of four days TPP still had a potent effect on the enzyme activity and the seminal vesicle, whereas T was almost without effect. Prolonged administration showed that the effects on the enzyme activity and the seminal vesicle of N and NPP could not reach the maximum effects of T and TPP respectively.


1977 ◽  
Vol 74 (3) ◽  
pp. 375-382 ◽  
Author(s):  
J. T. M. VREEBURG ◽  
PAULA D. M. VAN DER VAART ◽  
P. VAN DER SCHOOT

SUMMARY An inhibitor of aromatization, androsta-1,4,6-triene-3,17-dione (ATD), was administered to newborn male and female rats and various parameters of gonadal and sexual function were examined in adulthood. Males injected with 1 mg ATD on the day of birth (day 1) and on days 3, 5, 10 and 15 postnatally, subsequently (day 55) showed normal male and female copulatory behaviour, but were not able to maintain cyclicity in ovarian transplants. When the ATD was administered by Silastic implants, however, cyclicity in ovarian transplants did occur. Neither form of treatment brought about significant changes in neonatal plasma or testicular testosterone concentrations. Female rats implanted on day 3 of life with Silastic capsules containing ATD and then given an injection of 0·25 mg testosterone propionate on day 5 subsequently showed normal ovarian function, whereas the controls receiving only testosterone propionate showed persistent vaginal cornification, anovulation and polyfollicular ovaries. The results support the view that the central conversion of testicular androgens to oestrogens during the neonatal period is necessary to abolish cyclic gonadotrophin release and to suppress female copulatory behaviour.


1978 ◽  
Vol 78 (1) ◽  
pp. 31-38 ◽  
Author(s):  
G. VANDOREN ◽  
H. VAN BAELEN ◽  
G. VERHOEVEN ◽  
P. DE MOOR

Evidence is presented that the level of α2u-globulin in the serum of male rats depends, at least in part, on neonatal androgens. After castration of adult animals the concentration of this protein falls but remains measurable, whereas in intact or ovariectomized female rats α2u-globulin cannot be detected. Moreover, α2u-globulin is found in adult male and female rats gonadectomized at birth and treated with a single injection of testosterone propionate immediately thereafter. The mechanism by which neonatal androgens increase the concentration of α2u-globulin has been investigated. Transplantation of a supplementary pituitary gland under the renal capsule of male rats resulted in reduced levels of α2u-globulin and increased levels of transcortin. The changes discussed here were observed only in those animals in which the transplant was functional and they were amplified or reversed by modulators of prolactin secretion such as oestrogens or bromocriptine respectively. The hypothesis is advanced that neonatal androgens stimulate the production of a hypothalamic inhibitory factor that controls the secretion of prolactin, or another hypophysial hormone subjected to similar neuroendocrine control. Measurements in gonadectomized animals and in rats receiving both oestradiol benzoate and bromocriptine indicate that, besides these pituitary-mediated effects, both oestrogens and androgens exert direct effects on the level of α2u-globulin.


1974 ◽  
Vol 144 (2) ◽  
pp. 225-229 ◽  
Author(s):  
J-Å Gustafsson

The activities of the hepatic microsomal 2α-, 2β-, 7α- and 18-hydroxylase systems active on 5α-[4-14C]androstane-3α,17β-diol were studied in male and female rats which had been castrated at birth and at the age of 7, 13, 21, 27, 34, 43 and 55 days, treated for 5 days with 2mg of testosterone propionate/kg body weight and killed 6 days after castration. The 7α-hydroxylase system was affected very little by androgen treatment at all stages during development. On the other hand it was found that the rat liver passed through three phases during development with respect to androgen responsiveness as judged by changes in the activities of the 2α, 2β- and 18-hydroxylase systems: a first phase (from the neonatal period up to about 19 days of age) with a relative androgen unresponsiveness in both male and female rats, a second phase (from about 27 to about 33 days of age) when male and female rats responded equally well to androgens and a final phase (from about 40 days of age) with a successively decreasing androgen responsiveness in female rats but with a retained responsiveness in male rats. The hypothesis is presented that neonatal imprinting of the liver by testicular androgen(s) determines the development and degree of androgen responsiveness of liver tissue in the rat.


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.


1963 ◽  
Vol 26 (4) ◽  
pp. 517-523 ◽  
Author(s):  
K. BROWN-GRANT ◽  
W. TAYLOR

SUMMARY The effects of testosterone propionate (TP) and of 17α-ethyl-19 nor-testosterone (ENT) on the submandibular glands, levator ani muscles and seminal vesicles of castrated mice have been compared. ENT restores submandibular weight and histology about as well as TP but has less effect on the levator ani muscle and much less effect on the seminal vesicles. Both steroids can act directly on the submandibular gland. It is suggested that the effect on the gland may be an indication of the 'anabolic' rather than the 'androgenic' potency of the steroids, and the possible use of this response for the assay of 'anabolic' steroids is discussed.


1978 ◽  
Vol 79 (1) ◽  
pp. 135-136 ◽  
Author(s):  
G. VANDOREN ◽  
W. HEYNS ◽  
G. VERHOEVEN ◽  
P. DE MOOR

Laboratorium voor Experiméntele Geneeskunde, Katholieke Universiteit Leuven, Rega Instituut, Minderbroedersstraat 10, B-3000 Leuven, Belgium (Received 28 March 1978) The synthesis of α2u-globulin, the major protein found in the urine of adult male rats (Roy & Neuhaus, 1966; Roy, Neuhaus & Harmison, 1966), is controlled by several hormones. Androgens, growth hormone, thyroxine and glucocorticoids promote the synthesis of this protein, whereas oestrogens and a factor secreted by ectopically transplanted pituitary glands suppress it (Roy & Neuhaus, 1967; Roy, 1973; Kurtz, Sippel & Feigelson, 1976; Vandoren, Van Baelen, Verhoeven & De Moor, 1978). Cyproterone acetate (CA), a potent antiandrogen, inhibits the androgenic induction of α2u-globulin in ovariectomized rats, but does not suppress its synthesis in intact male rats (Roy, 1976). In the present experiments, the influence of CA on the induction of α2u-globulin by testosterone propionate (TP) in the serum of gonadectomized male and female rats was compared. Evidence is presented for


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.


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