Document Detail


The effect of inhibition of aromatase enzyme activity on Leydig cell number and ultrastructure in beagles.
MedLine Citation:
PMID:  2971525     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have shown previously that administration of an orally active competitive aromatase inhibitor 4-(5,6,7,8-tetrahydroimidazo [1,5a] pyridin-5-yl) benzonitrile monohydrochloride to adult male beagles increases peripheral blood LH and testosterone concentrations, and that testes from treated dogs produce more testosterone when perfused in vitro than age-matched controls. In the present study we posed the question of whether the increased testosterone secretion by testes from these same aromatase-treated dogs was due to Leydig cell hypertrophy or hyperplasia, and if the latter, whether cytoplasmic organelles are increased. Beagles were treated with the inhibitor at a dosage of 2.5 mg/kg.day for 25 weeks and were euthanized by an overdose of iv sodium pentobarbital; testes were perfusion-fixed, embedded, and sectioned for stereological analysis. There were no significant differences in testis volume and absolute volumes of seminiferous tubules, blood vessels, lymphatic space, macrophage cells, and mesenchymal cells between the control and treated dogs. In contrast absolute interstitium volume and the absolute volume of Leydig cells per testis were significantly increased (P less than 0.05) in treated dogs. This increased Leydig cell volume per testis was due to increased volume of individual Leydig cells rather than to increases in Leydig cell number per testis. Additional studies showed that the surface area per Leydig cell of smooth endoplasmic reticulum, outer and inner mitochondrial membranes, and membranes of lipid droplets per testis were significantly higher (P less than 0.05) in the treated dogs as compared to the controls. In summary, the results of this study lead us to conclude that aromatase inhibition in the mature dog causes Leydig cell hypertrophy rather than hyperplasia and increased surface area per Leydig cell of subcellular organelles that contain enzymes involved in steroid biosynthesis.
Authors:
J R Walters; P E Juniewicz; J E Oesterling; S M Mendis-Handagama; B R Zirkin; L L Ewing
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Endocrinology     Volume:  123     ISSN:  0013-7227     ISO Abbreviation:  Endocrinology     Publication Date:  1988 Nov 
Date Detail:
Created Date:  1988-11-21     Completed Date:  1988-11-21     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2223-9     Citation Subset:  AIM; IM    
Affiliation:
Department of Population Dynamics, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland 21205.
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MeSH Terms
Descriptor/Qualifier:
Animals
Aromatase Inhibitors*
Cell Count
Dogs
Endoplasmic Reticulum / ultrastructure
Fadrozole
Imidazoles / pharmacology*
Leydig Cells / drug effects,  ultrastructure*
Lipid Metabolism
Male
Microscopy, Electron
Mitochondria / ultrastructure
Nitriles / pharmacology*
Organelles / ultrastructure
Testis / cytology
Grant Support
ID/Acronym/Agency:
2-P30 HD06208/HD/NICHD NIH HHS; AM 193000/AM/NIADDK NIH HHS; F32 HD06452/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Aromatase Inhibitors; 0/Imidazoles; 0/Nitriles; 102676-47-1/Fadrozole

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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