THE ASSAY OF SUBCUTANEOUSLY INJECTED ANDROGENS IN THE CASTRATED RAT

1963 ◽  
Vol 42 (2) ◽  
pp. 245-253 ◽  
Author(s):  
Ralph I. Dorfman ◽  
Adeline S. Dorfman

ABSTRACT An assay procedure using the immature castrated albino rat is described using the weight of the seminal vesicles, ventral prostate, and levator ani as end-points in a ten day assay. The sensitivity was of the order of 0.6 mg of testosterone injected subcutaneously once daily in an aqueous suspending medium. The precision was adequate as judged by the λ values of 0.096 to 0.137 for the seminal vesicles, 0.128 to 0.162 for the ventral prostate, and 0.171 to 0.248 for the levator ani. Activity of testosterone was increased significantly by esterification, by introduction of the 17α-methyl group, and by reduction of the Δ4 double bond to the 5α form. Androgenic activity was decreased significantly by oxidation of the 17β-hydroxy group to the 17-keto group and introduction of methyl groups at the 2α- or 6α-positions.

1962 ◽  
Vol 41 (2) ◽  
pp. 265-267 ◽  
Author(s):  
Ralph I. Dorfman

ABSTRACT An oral assay 10-day procedure for bioassay of androgens is described using the immature castrated male albino rat and the end-points of seminal vesicles, ventral prostate, and levator ani tissues. No particular gain in precision could be achieved by extending the assay procedure beyond ten days. Using single daily doses and an aqueous suspending medium, the λ value for the seminal vesicles was 0.210, for the ventral prostate it was 0.190, and 0.218 for the levator ani. The present experiments were carried out with fluoxymesterone.


1972 ◽  
Vol 180 (1059) ◽  
pp. 125-146 ◽  

Lanosterol(4,4,14α-trimethyl-cholesta-8,24-dien-3β-ol) has been proposed as the primary product of the cyclization of 2,3-epoxysqualene in animal tissues. Enzymic conversion of lanosterol to cholesterol requires reduction of the ∆ 24 double bond, removal of the three extra methyl groups, and shift of the nuclear double bond from ∆ 8 position to the ∆ 5 position. Until very recently, all of the proposed sterol intermediates in the biosynthesis of cholesterol possessed nuclear double bonds in the ∆ 8 , ∆ 7 , ∆ 5,7 or ∆ 5 positions. Consideration of possible mechanisms for the removal of the methyl group at carbon atom 14 of sterol precursors led to our demonstration of the presence of cholest-8(14)-en-3β-ol in animal tissues and establishment of the convertibility of this sterol to cholesterol in rat liver homogenate preparations. Reports (from other laboratories) of the stereospecific loss of the 15α-hydrogen of lanosterol upon enzymic conversion to cholesterol led to the demonstration of the convertibility of cholesta-8,14-dien-3β-ol, cholesta-7,14-dien-3β-ol, 14α-methyl-cholest-7-en-3β,15-diol, cholest-8(14)-en-3β,15α-diol, and cholest-8(14)-en-3β,15β-diol to cholesterol in rat liver preparations. We have recently developed chromatographic methods permitting the resolution of all of the C 27 sterols in question. The results of recent experiments directed towards an understanding of the detailed metabolism of these compounds are presented herein.


1959 ◽  
Vol XXXII (IV) ◽  
pp. 536-544 ◽  
Author(s):  
J. G. Llaurado ◽  
J. B. Trunnell ◽  
J. L. Claus

ABSTRACT An investigation was undertaken in an attempt to determine whether norethandrolone (NEA) antagonizes all or some of the catabolic effects of 17-hydroxycorticoids. Fourteen groups of eight male young rats (intact, gonadectomized, adrenalectomized and adrenalectomized-gonadectomized) were given subcutaneously either the solvent, NEA (1 mg/day), cortisone (1 mg/day) or a combination of both for 21 days. Results show that administration of NEA has a moderate but consistent effect in increasing body weight of rats receiving no other steroid as well as in preventing the delayed growth rate of those receiving cortisone. In both intact and gonadectomized animals, NEA largely prevented the intense atrophy of the adrenals induced by cortisone. An increase in levator ani weight was promoted by NEA regardless of concurrent administration of cortisone. The latter induced a diminution in the size of seminal vesicles, coagulating glands and ventral prostate, whereas NEA had the opposite effect; when given together the effect of NEA was potentiated. Treatment with NEA alone was shown to have a marked thymolytic effect and also to potentiate the thymolytic effect of cortisone when given together. These results suggest that in some tissues NEA antagonizes, and in others augments, some of the catabolic actions of 17-hydroxycorticoids


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.


1966 ◽  
Vol 53 (4) ◽  
pp. 635-643 ◽  
Author(s):  
E. F. Nutting ◽  
P. D. Klimstra ◽  
R. E. Counsell

ABSTRACT The oral activity of 34 steroids administered by stomach catheter was evaluated in castrated rats using the weights of the seminal vesicle glands and ventral lobe of the prostate glands as independent parameters of androgenicity and the weight of the levator ani muscle was used as an index of anabolic activity. 17α-Methyltestosterone was used as the reference standard. A study of various modifications of the A-ring revealed that biological activity was consistent with any one of several distinct changes and did not appear to be related to the electron density in any specific position in the A-ring. Nineteen of the steroids were more potent anabolically than the standard and the eight most active analogues had relative myotrophic potencies ranging from 420–1200% and myotrophic to androgenic ratios ranging from 4.1 to 9.3, respectively. Both saturated and unsaturated 17α-methyl derivatives were represented in this latter group. In general, the most potent compounds anabolically were also among the most active androgenically. Estimates of androgenic potency obtained from the seminal vesicle response were similar to those obtained from the ventral prostate response. The most active anabolic compound (1200%) was the 2-dehydro derivative of 17α-methyl-5α-androstan-17β-ol. The widest separation between anabolic and androgenic activities, myotrophic to androgenic ratio of 9.3, was produced with the 2-dehydro-1α-methyl derivative.


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.


1967 ◽  
Vol 55 (1) ◽  
pp. 119-130 ◽  
Author(s):  
Cesare Cavallero

ABSTRACT Morphological studies have shown that the exorbital lacrimal gland of the albino rat is a sexually dimorphic structure highly sensitive to androgens. Testosterone treatment elicits a vesicular-mucous change in the glandular acini which can be quantitated histologically and appears to be closely related to the administered dose. An assay procedure using the vesicular change as the end-point of androgenic activity is described and the relative androgenic activities of twenty-one Δ4-3-keto- and Δ5-3β-hydroxysteroids are given. The effect of a variety of substitutions in the steroid nucleus on the activities of testosterone, 17α-methyl-testosterone and 19-nortestosterone is described and discussed with reference to previously reported data.


2000 ◽  
Vol 68 (2) ◽  
pp. 141-157 ◽  
Author(s):  
Y. A. Maklad ◽  
M. M. Nosseir

Derivatives of eplandrosterone and progesterone were synthesized. The androgenic and the anabolic activities of some of tlieln were investigated on prepubertal male albino rats of 21 days old by:-i determining tlie weight gain of the body, levator ani muscle, ventral prostate gland, testis, selniilal vesicles, vas deferens and epididymis, ii- estimation of serum luteinizing (LH) hormone, iii- histopatliological examination of the testis and ventral prostate glands. The results from this study showed that the presence of an appended substituted 2- aminopyridine ring at the C- 17 of testosterone gave the maximum androgenic activity, whereas the presence of a substituted piperidine ring fused to ring D of 5 α- androstane exhibited tlie maximum anabolic activity. However, fusion of a pyrazoline moiety with the ring D of 5 α- androstane led to a compound with considerable androgenic and anabolic activity.


1970 ◽  
Vol 64 (4) ◽  
pp. 637-655 ◽  
Author(s):  
Lars-Eric Tisell

ABSTRACT The growth of the ventral and the dorsolateral prostate, the coagulating glands and the seminal vesicles was studied in cortisone-treated and non-treated castrated non-adrenalectomized and castrated adrenalectomized rats. The cortisone was administered in daily doses of 3 mg or 9 mg for a period of 15 days. Combined castration and adrenalectomy resulted in a greater degree of atrophy of the ventral prostate than castration alone, thus indicating some maintenance effect of the adrenals on the ventral prostate. No differences in the other accessory reproductive organs were demonstrated when comparing non-treated castrated non-adrenalectomized with castrated adrenalectomized rats. Both doses of cortisone stimulated the growth of the dorsolateral prostate, the coagulating glands and the seminal vesicles, but the larger dose resulted in a greater degree of stimulation. Only the larger dose of cortisone gave histological changes in the ventral prostate indicative of a slight stimulating effect. Catabolic or anti-anabolic effects of cortisone as registered by a decrease in body weight and weight of the levator ani muscle did not inhibit the growth stimulating effect of cortisone on the accessory reproductive organs. Cortisone stimulated the growth of both the epithelium and the smooth muscle tissue of the glands. The effect on the different accessory reproductive organs after cortisone administration was contrary to previous studies, which demonstrated the stimulating effects of androgens in the rat, in that the ventral prostate was relatively unstimulated. Possible mechanisms for the stimulation of the growth of the accessory reproductive organs are discussed in the light of our present knowledge of cortisone metabolism and of the secretion in the cortisone-treated rats of hormones which have been found to modify the growth of the accessory reproductive organs.


1972 ◽  
Vol 69 (1) ◽  
pp. 165-173 ◽  
Author(s):  
H. Schmidt ◽  
I. Noack ◽  
K. D. Voigt

ABSTRACT The effect of testosterone and 5α-dihydrotestosterone on protein and nucleic acid content as well as on the activities of some enzymes has been studied in the ventral prostate and the seminal vesicles of immature castrated rats. Both androgens were given intraperitoneally in doses of 1 mg daily for one or three days the rats were sacrificed one day after the last injection. In the prostate it was found that 5α-dihydrotestosterone had a greater effect on DNA increase, i. e. cell proliferation than testosterone, whereas cell metabolism was stimulated by the two androgens to nearly the same extent. In the seminal vesicles a single dose led to the same results as had been obtained in the prostate, i. e. a greater cell proliferative action of 5α-dihydrotestosterone and an equal stimulation of cell metabolism by testosterone and 5α-dihydrotestosterone was also observed. When three doses of the two androgens were given, cell proliferation as well as cell metabolism in the seminal vesicles were significantly more increased after 5α-dihydrotestosterone than after testosterone. The difference of action after systemic administration of the two androgens is explained by their different accumulation and by their different peripheral metabolism in the target tissues. From the partly independent effects of various androgens on cell proliferation and cell metabolism the conclusion may be drawn that there exist at least two intracellular sites of action.


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