Effect of a nonsteroidal antiandrogen, Anandron, on the reproductive system and fertility in male rats
The effect of Anandron, a nonsteroidal antiandrogen, on the reproductive system and fertility of adult male rats was studied. Administered at a daily oral dose of 5 mg and 10 mq (per rat) for 30 days, it caused a significant increase in the plasma testosterone levels. Spermatogenic arrest in about 2...
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Published in | Contraception (Stoneham) Vol. 42; no. 1; pp. 121 - 138 |
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Main Authors | , |
Format | Journal Article |
Language | English |
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New York, NY
Elsevier Inc
01.07.1990
Elsevier Science |
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Abstract | The effect of Anandron, a nonsteroidal antiandrogen, on the reproductive system and fertility of adult male rats was studied. Administered at a daily oral dose of 5 mg and 10 mq (per rat) for 30 days, it caused a significant increase in the plasma testosterone levels. Spermatogenic arrest in about 20 to 50% of the tubules in 9 out of 16 rats and stimulation of Leydig cells was observed in rats treated with the higher dose. Although a reduction occurred in accessory sex organ (epididymis, seminal vesicles, SV; ventral prostate, VP; dorsal prostate, DP and coagulating gland, CG) weight, no parallel reduction was evident in the secretory indices of the epididymis (glycerylphosphorylcholine and sialic acid), VP (alkaline phosphatase) and CG (fructose). However, there was a reduction in the total content per organ of these constituents. Females mated with treated males showed postimplantation loss indicating an adverse effect of Anandron during spermiogenesis. The results suggest that the peripheral antiandrogenic potency of Anandron in intact animals is insufficient to completely neutralize the elevated levels of androgens. A microdose (1 μg) of estradiol efficiently neutralized the central stimulatory effect of Anandron and potentiated its antiandrogenic action. The potential use of such a combination for ‘Fertility Regulation’ in male is discussed. |
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AbstractList | The effect of Anandron, a nonsteroidal antiandrogen, on the reproductive system and fertility of adult male rats was studied. Administered at a daily oral dose of 5 mg and 10 mg (per rat) for 30 days, it caused a significant increase in the plasma testosterone levels. Spermatogenic arrest in about 20 to 50% of the tubules in 9 out of 16 rats and stimulation of Leydig cells was observed in rats treated with the higher dose. Although a reduction occurred in accessory sex organ (epididymis, seminal vesicles, SV; ventral prostate, VP; dorsal prostate, DP and coagulating gland, CG) weight, no parallel reduction was evident in the secretory indices of the epididymis (glycerylphosphorylcholine and sialic acid), VP (alkaline phosphatase) and CG (fructose). However, there was a reduction in the total content per organ of these constituents. Females mated with treated males showed postimplantation loss indicating an adverse effect of Anandron during spermiogenesis. The results suggest that the peripheral antiandrogenic potency of Anandron in intact animals is insufficient to completely neutralize the elevated levels of androgens. A microdose (1 microgram) of estradiol efficiently neutralized the central stimulatory effect of Anadron and potentiated its antiandrogenic action. The potential use of such a combination for 'Fertility Regulation' in male is discussed. The effect of Anandron, a nonsteroidal antiandrogen, on the reproductive system and fertility of adult male rats was studied. Administered at a daily oral dose of 5 mg and 10 mq (per rat) for 30 days, it caused a significant increase in the plasma testosterone levels. Spermatogenic arrest in about 20 to 50% of the tubules in 9 out of 16 rats and stimulation of Leydig cells was observed in rats treated with the higher dose. Although a reduction occurred in accessory sex organ (epididymis, seminal vesicles, SV; ventral prostate, VP; dorsal prostate, DP and coagulating gland, CG) weight, no parallel reduction was evident in the secretory indices of the epididymis (glycerylphosphorylcholine and sialic acid), VP (alkaline phosphatase) and CG (fructose). However, there was a reduction in the total content per organ of these constituents. Females mated with treated males showed postimplantation loss indicating an adverse effect of Anandron during spermiogenesis. The results suggest that the peripheral antiandrogenic potency of Anandron in intact animals is insufficient to completely neutralize the elevated levels of androgens. A microdose (1 μg) of estradiol efficiently neutralized the central stimulatory effect of Anandron and potentiated its antiandrogenic action. The potential use of such a combination for ‘Fertility Regulation’ in male is discussed. |
Author | Setty, B.S. Dhar, J.D. |
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Cites_doi | 10.1210/jcem-59-3-422 10.1002/pros.2990040605 10.1016/0303-7207(84)90047-9 10.1042/bj0400481 10.1016/0303-7207(81)90028-9 10.1002/pros.2990130108 10.1016/0022-4731(79)90281-4 10.1016/S0015-0282(16)41840-6 10.1136/jcp.7.4.322 10.1042/bj0810384 10.1038/icb.1959.45 10.1016/S0021-9258(19)52451-6 10.1530/acta.0.1020299 10.1016/0022-4731(88)90024-6 10.1016/0022-4731(87)90122-1 10.1002/pros.2990050307 10.1530/acta.0.1040246 |
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Keywords | Rat Spermatogenesis Rodentia Antiandrogen Male Contraception Male genital system Biological activity Vertebrata Epididymis Mammalia Fertility Animal |
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References | Rao, Geldof, Vander Vilt, de Voogt (BIB8) 1988; 13 Dhar, Setty (BIB19) 1987; 25 Seguin, Cusan, Belanger, Kelly, Labrie, Raynaud (BIB4) 1981; 21 Viguier-Martinez, Hochereau de Reviers, Barenton, Perreau (BIB17) 1983; 104 Hawk, Oser, Summerson (BIB11) 1957 Aminoff (BIB10) 1961; 81 Viguier-Martinez, Hochereau de Reviers, Barenton, Perreau (BIB16) 1983; 102 Raynaud, Bonne, Bouton, Lagace, Labre (BIB2) 1979; 11 Mann (BIB14) 1946; 40 Pao, Nussberger, Brunner (BIB6) 1988; 31 Kind, King (BIB13) 1954; 7 Ayub, Levell (BIB15) 1987; 28 Tenniswood, Abrahams, Bird, Clark (BIB20) 1984; 37 Lowry, Rosebrough, Farr, Randall (BIB12) 1951; 193 Labrie, Dupont, Belanger, Lacoursiere, Raynaud, Husson, Gareau, Fazekas, Sandow, Monfette, Girard, Emond, Houle (BIB7) 1983; 4 Setty (BIB1) 1979; 74 Raynaud, Bonne, Moguilewsky, Lefebvre, Belanger, Labrie (BIB3) 1984; 5 White (BIB9) 1959; 37 Belanger, Dupont, Labrie (BIB5) 1984; 59 Dhar, Setty (BIB18) 1976; 27 Labrie (10.1016/0010-7824(90)90096-E_BIB7) 1983; 4 Pao (10.1016/0010-7824(90)90096-E_BIB6) 1988; 31 Viguier-Martinez (10.1016/0010-7824(90)90096-E_BIB17) 1983; 104 Raynaud (10.1016/0010-7824(90)90096-E_BIB2) 1979; 11 White (10.1016/0010-7824(90)90096-E_BIB9) 1959; 37 Mann (10.1016/0010-7824(90)90096-E_BIB14) 1946; 40 Ayub (10.1016/0010-7824(90)90096-E_BIB15) 1987; 28 Kind (10.1016/0010-7824(90)90096-E_BIB13) 1954; 7 Raynaud (10.1016/0010-7824(90)90096-E_BIB3) 1984; 5 Aminoff (10.1016/0010-7824(90)90096-E_BIB10) 1961; 81 Rao (10.1016/0010-7824(90)90096-E_BIB8) 1988; 13 Lowry (10.1016/0010-7824(90)90096-E_BIB12) 1951; 193 Tenniswood (10.1016/0010-7824(90)90096-E_BIB20) 1984; 37 Hawk (10.1016/0010-7824(90)90096-E_BIB11) 1957 Dhar (10.1016/0010-7824(90)90096-E_BIB19) 1987; 25 Setty (10.1016/0010-7824(90)90096-E_BIB1) 1979; 74 Belanger (10.1016/0010-7824(90)90096-E_BIB5) 1984; 59 Viguier-Martinez (10.1016/0010-7824(90)90096-E_BIB16) 1983; 102 Dhar (10.1016/0010-7824(90)90096-E_BIB18) 1976; 27 Seguin (10.1016/0010-7824(90)90096-E_BIB4) 1981; 21 |
References_xml | – volume: 21 start-page: 37 year: 1981 end-page: 41 ident: BIB4 article-title: Additive inhibitory effects of treatment with an LHRH agonist and an antiandrogen in androgen depen-dent tissues in the rat publication-title: Mol Cell Endocr contributor: fullname: Raynaud – volume: 31 start-page: 731 year: 1988 end-page: 738 ident: BIB6 article-title: Merits and considerations in the use of antiandrogens publication-title: J Steroid Biochem contributor: fullname: Brunner – volume: 11 start-page: 93 year: 1979 end-page: 99 ident: BIB2 article-title: Action of a non-steroid antiandrogen, RU 23908, in peripheral and central tissues publication-title: J Steroid Biochem contributor: fullname: Labre – volume: 4 start-page: 579 year: 1983 end-page: 594 ident: BIB7 article-title: New approach in the treatment of prostate cancer: complete instead of only partial withdrawal of androgens publication-title: The Prostate contributor: fullname: Houle – volume: 81 start-page: 384 year: 1961 end-page: 392 ident: BIB10 article-title: Methods for the quantitative estimation of N-acetylneuraminic acid and application to hydrolysates of sialomucoids publication-title: Biochem J contributor: fullname: Aminoff – volume: 59 start-page: 422 year: 1984 end-page: 426 ident: BIB5 article-title: Inhibition of basal and adrenocorticotropin stimulated levels of adrenal androgens after treatment with an antiandrogen in castrated patients with prostatic cancer publication-title: J Clin Endocrinol Metab contributor: fullname: Labrie – volume: 40 start-page: 481 year: 1946 end-page: 491 ident: BIB14 article-title: Fructose as a normal constituent of seminal plasma. Site of formation and function of fructose in semen publication-title: Biochem J contributor: fullname: Mann – volume: 74 start-page: 100 year: 1979 end-page: 117 ident: BIB1 article-title: Regulation of epididymal function and sperm maturation. Endocrine approach to fertility control publication-title: Endokrinol contributor: fullname: Setty – start-page: 112 year: 1957 end-page: 116 ident: BIB11 article-title: Lipids publication-title: Practical Physiological Chemistry contributor: fullname: Summerson – volume: 37 start-page: 153 year: 1984 end-page: 158 ident: BIB20 article-title: Antiandrogens do not alter androgen-dependent characteristics of acid phosphatase in rat ventral prostate publication-title: Mol Cell Endocrinol contributor: fullname: Clark – volume: 13 start-page: 69 year: 1988 end-page: 78 ident: BIB8 article-title: Efficacy and advantages in the use of low doses of Anandron and estrogen combination in the treatment of prostate cancer publication-title: The Prostate contributor: fullname: de Voogt – volume: 25 start-page: 81 year: 1987 end-page: 85 ident: BIB19 article-title: Effect of flutamide, a nonsteroidal antiandrogen on testis and accessory genital organs of male rats. A re-evaluation in adult and prepubertal rat publication-title: Ind J Expt Biol contributor: fullname: Setty – volume: 193 start-page: 265 year: 1951 end-page: 275 ident: BIB12 article-title: Protein measurement with Folin phenol reagent publication-title: J Biol Chem contributor: fullname: Randall – volume: 37 start-page: 441 year: 1959 end-page: 450 ident: BIB9 article-title: Studies on the estimation of glycerol, fructose and lactic acid with particular reference to semen publication-title: Austral J Exper Biol & Med contributor: fullname: White – volume: 28 start-page: 43 year: 1987 end-page: 47 ident: BIB15 article-title: Inhibition of rat testicular 17-hydroxylase and 17,20-lyase activities by antiandrogens (flutamide, hydroxyflutamide, RU 23908, cyproterone acetate) in vitro publication-title: J Steroid Biochem contributor: fullname: Levell – volume: 27 start-page: 566 year: 1976 end-page: 576 ident: BIB18 article-title: Studies on the physiology and biochemistry of mammalian epididymis. Effect of flutamide, a nonsteroidal antiandrogen, on the epididymis of the rat publication-title: Fertil Steril contributor: fullname: Setty – volume: 5 start-page: 299 year: 1984 end-page: 311 ident: BIB3 article-title: The pure antiandrogen RU 23908 (Anandron), a candidate of choice for the combined antihormonal treatment of prostatic cancer publication-title: A review. The Prostate contributor: fullname: Labrie – volume: 7 start-page: 322 year: 1954 end-page: 326 ident: BIB13 article-title: Determination of plasma phos- phatase by determination of hydrolysed phenol with amino-anti- pyrine publication-title: J Clin Pathol contributor: fullname: King – volume: 102 start-page: 299 year: 1983 end-page: 306 ident: BIB16 article-title: Effect of a non-steroidal antiandrogen, flutamide, on the hypothalamo-pituitary axis, genital tract and testis in growing male rats: endocrinological and histological data publication-title: Acta Endocrinologica contributor: fullname: Perreau – volume: 104 start-page: 246 year: 1983 end-page: 252 ident: BIB17 article-title: Endocrinological changes and histological changes induced by flutamide on the hypothalamo-hypo- physeal-testicular axis of the adult male rat and their incidences of fertility publication-title: Acta Endocrinologica contributor: fullname: Perreau – volume: 59 start-page: 422 year: 1984 ident: 10.1016/0010-7824(90)90096-E_BIB5 article-title: Inhibition of basal and adrenocorticotropin stimulated levels of adrenal androgens after treatment with an antiandrogen in castrated patients with prostatic cancer publication-title: J Clin Endocrinol Metab doi: 10.1210/jcem-59-3-422 contributor: fullname: Belanger – volume: 4 start-page: 579 year: 1983 ident: 10.1016/0010-7824(90)90096-E_BIB7 article-title: New approach in the treatment of prostate cancer: complete instead of only partial withdrawal of androgens publication-title: The Prostate doi: 10.1002/pros.2990040605 contributor: fullname: Labrie – volume: 74 start-page: 100 year: 1979 ident: 10.1016/0010-7824(90)90096-E_BIB1 article-title: Regulation of epididymal function and sperm maturation. Endocrine approach to fertility control publication-title: Endokrinol contributor: fullname: Setty – volume: 37 start-page: 153 year: 1984 ident: 10.1016/0010-7824(90)90096-E_BIB20 article-title: Antiandrogens do not alter androgen-dependent characteristics of acid phosphatase in rat ventral prostate publication-title: Mol Cell Endocrinol doi: 10.1016/0303-7207(84)90047-9 contributor: fullname: Tenniswood – volume: 40 start-page: 481 year: 1946 ident: 10.1016/0010-7824(90)90096-E_BIB14 article-title: Fructose as a normal constituent of seminal plasma. Site of formation and function of fructose in semen publication-title: Biochem J doi: 10.1042/bj0400481 contributor: fullname: Mann – volume: 21 start-page: 37 year: 1981 ident: 10.1016/0010-7824(90)90096-E_BIB4 article-title: Additive inhibitory effects of treatment with an LHRH agonist and an antiandrogen in androgen depen-dent tissues in the rat publication-title: Mol Cell Endocr doi: 10.1016/0303-7207(81)90028-9 contributor: fullname: Seguin – volume: 13 start-page: 69 year: 1988 ident: 10.1016/0010-7824(90)90096-E_BIB8 article-title: Efficacy and advantages in the use of low doses of Anandron and estrogen combination in the treatment of prostate cancer publication-title: The Prostate doi: 10.1002/pros.2990130108 contributor: fullname: Rao – volume: 11 start-page: 93 year: 1979 ident: 10.1016/0010-7824(90)90096-E_BIB2 article-title: Action of a non-steroid antiandrogen, RU 23908, in peripheral and central tissues publication-title: J Steroid Biochem doi: 10.1016/0022-4731(79)90281-4 contributor: fullname: Raynaud – volume: 27 start-page: 566 year: 1976 ident: 10.1016/0010-7824(90)90096-E_BIB18 article-title: Studies on the physiology and biochemistry of mammalian epididymis. Effect of flutamide, a nonsteroidal antiandrogen, on the epididymis of the rat publication-title: Fertil Steril doi: 10.1016/S0015-0282(16)41840-6 contributor: fullname: Dhar – start-page: 112 year: 1957 ident: 10.1016/0010-7824(90)90096-E_BIB11 article-title: Lipids contributor: fullname: Hawk – volume: 7 start-page: 322 year: 1954 ident: 10.1016/0010-7824(90)90096-E_BIB13 article-title: Determination of plasma phos- phatase by determination of hydrolysed phenol with amino-anti- pyrine publication-title: J Clin Pathol doi: 10.1136/jcp.7.4.322 contributor: fullname: Kind – volume: 25 start-page: 81 year: 1987 ident: 10.1016/0010-7824(90)90096-E_BIB19 article-title: Effect of flutamide, a nonsteroidal antiandrogen on testis and accessory genital organs of male rats. A re-evaluation in adult and prepubertal rat publication-title: Ind J Expt Biol contributor: fullname: Dhar – volume: 81 start-page: 384 year: 1961 ident: 10.1016/0010-7824(90)90096-E_BIB10 article-title: Methods for the quantitative estimation of N-acetylneuraminic acid and application to hydrolysates of sialomucoids publication-title: Biochem J doi: 10.1042/bj0810384 contributor: fullname: Aminoff – volume: 37 start-page: 441 year: 1959 ident: 10.1016/0010-7824(90)90096-E_BIB9 article-title: Studies on the estimation of glycerol, fructose and lactic acid with particular reference to semen publication-title: Austral J Exper Biol & Med doi: 10.1038/icb.1959.45 contributor: fullname: White – volume: 193 start-page: 265 year: 1951 ident: 10.1016/0010-7824(90)90096-E_BIB12 article-title: Protein measurement with Folin phenol reagent publication-title: J Biol Chem doi: 10.1016/S0021-9258(19)52451-6 contributor: fullname: Lowry – volume: 102 start-page: 299 year: 1983 ident: 10.1016/0010-7824(90)90096-E_BIB16 article-title: Effect of a non-steroidal antiandrogen, flutamide, on the hypothalamo-pituitary axis, genital tract and testis in growing male rats: endocrinological and histological data publication-title: Acta Endocrinologica doi: 10.1530/acta.0.1020299 contributor: fullname: Viguier-Martinez – volume: 31 start-page: 731 year: 1988 ident: 10.1016/0010-7824(90)90096-E_BIB6 article-title: Merits and considerations in the use of antiandrogens publication-title: J Steroid Biochem doi: 10.1016/0022-4731(88)90024-6 contributor: fullname: Pao – volume: 28 start-page: 43 year: 1987 ident: 10.1016/0010-7824(90)90096-E_BIB15 article-title: Inhibition of rat testicular 17-hydroxylase and 17,20-lyase activities by antiandrogens (flutamide, hydroxyflutamide, RU 23908, cyproterone acetate) in vitro publication-title: J Steroid Biochem doi: 10.1016/0022-4731(87)90122-1 contributor: fullname: Ayub – volume: 5 start-page: 299 year: 1984 ident: 10.1016/0010-7824(90)90096-E_BIB3 article-title: The pure antiandrogen RU 23908 (Anandron), a candidate of choice for the combined antihormonal treatment of prostatic cancer publication-title: A review. The Prostate doi: 10.1002/pros.2990050307 contributor: fullname: Raynaud – volume: 104 start-page: 246 year: 1983 ident: 10.1016/0010-7824(90)90096-E_BIB17 article-title: Endocrinological changes and histological changes induced by flutamide on the hypothalamo-hypo- physeal-testicular axis of the adult male rat and their incidences of fertility publication-title: Acta Endocrinologica doi: 10.1530/acta.0.1040246 contributor: fullname: Viguier-Martinez |
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SubjectTerms | Alkaline Phosphatase - metabolism Androgen Antagonists - pharmacology Animals Biological and medical sciences Body Weight - drug effects Dose-Response Relationship, Drug Epididymis - drug effects Estradiol - pharmacology Fertility - drug effects Flutamide - pharmacology Fructose - metabolism Glycerylphosphorylcholine - metabolism Hormones. Endocrine system Imidazoles - pharmacology Imidazolidines Leydig Cells - drug effects Male Medical sciences N-Acetylneuraminic Acid Organ Size - drug effects Pharmacology. Drug treatments Phospholipids - analysis Prostate - drug effects Proteins - analysis Rats Rats, Inbred Strains Seminal Vesicles - drug effects Sialic Acids - metabolism Spermatogenesis - drug effects Testis - cytology Testis - drug effects Testosterone - blood Urogenital System - drug effects |
Title | Effect of a nonsteroidal antiandrogen, Anandron, on the reproductive system and fertility in male rats |
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