Document Detail


Effects of new multi-site hormone blockers on the fertility of male rats.
MedLine Citation:
PMID:  1270948     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The effects on the fertility of adult male rats of six new synthetic steroids: I, 3-cyano-5alpha-androst-1-en-17-one; II, the 17beta-acetate form of I; III, 17beta-hydroxy-5beta-cyano-androstan-3-one; IV, 6-methylpregnenolone; V, 17beta-hydroxy-17alpha-ethynyl-5beta-cyano-19-norandrostan-3-one; and VI, 19-norspiroxenone (oestr-4-en-3-one-spiro-17alpha-2'-[tetrahydrofuran]) have been tested. After 6 weeks of treatment with daily doses of 5 mg (I, II, III), 15 mg (IV) or 10 mg (V, VI) only steroid VI blocked the completion of spermatogenesis and reduced the number of foetuses sired in at least five females/male. Steroid VI also diminished seminal vesicular, prostatic, testicular and epididymal weights. It inhibited the testicular enzymes, 3beta-hydroxysteroid dehydrogenase-delta4-5-3-oxosteroid isomerase system, 17alpha-hydroxylase, and C17-20 lyase markedly, but did not affect the adrenal dehydrogenase-isomerase system. It depressed, strikingly, testicular and serum levels of testosterone and 5alpha-dihydrotestosterone and reduced pituitary and serum levels of FSH and LH. Although marked depression of target organ weights also occurred with steroids II, IV and V, and reduction of androgen levels and LH in the circulation with III, IV and V, only VI was a potent blocker of male fertility with the exception of a slight block of the siring of viable foetuses by steroids IV and V. The major difference in site of action of steroid VI from the others was the depression of pituitary and serum levels of FSH along with a marked diminution of testicular content of both testosterone and 5alpha-dihydrotestosterone. 19-Norspiroxenone in the rat is a potent anti-oestrogen without inherent oestrogenicity and is anti-uterotrophic. Thus, VI may affect male fertility by virtue of its potent anti-oestrogenic action in the hypothalamus or testis.
Authors:
A S Goldman; B H Shapiro; A W Root
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of endocrinology     Volume:  69     ISSN:  0022-0795     ISO Abbreviation:  J. Endocrinol.     Publication Date:  1976 Apr 
Date Detail:
Created Date:  1976-08-02     Completed Date:  1976-08-02     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  0375363     Medline TA:  J Endocrinol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  11-21     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Androstanes / pharmacology
Animals
Contraceptive Agents, Male / pharmacology*
Dihydrotestosterone / metabolism
Epididymis / drug effects
Estrenes / pharmacology
Fertility / drug effects*
Follicle Stimulating Hormone / blood
Furans / pharmacology
Hormone Antagonists / pharmacology*
Hydroxysteroid Dehydrogenases / antagonists & inhibitors
Luteinizing Hormone / blood
Male
Microsomes / drug effects
Mixed Function Oxygenases / antagonists & inhibitors
Pituitary Gland / analysis
Pregnanes / pharmacology
Prostate / drug effects
Rats
Seminal Vesicles / drug effects
Spermatogenesis / drug effects
Steroid Isomerases / antagonists & inhibitors
Testis / drug effects
Testosterone / metabolism
Chemical
Reg. No./Substance:
0/Androstanes; 0/Contraceptive Agents, Male; 0/Estrenes; 0/Furans; 0/Hormone Antagonists; 0/Pregnanes; 521-18-6/Dihydrotestosterone; 58-22-0/Testosterone; 9002-67-9/Luteinizing Hormone; 9002-68-0/Follicle Stimulating Hormone; EC 1.-/Mixed Function Oxygenases; EC 1.1.-/Hydroxysteroid Dehydrogenases; EC 5.3.3.-/Steroid Isomerases

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