Document Detail


Loratadine exerts estrogen-like effects and disrupts penile development in the mouse.
MedLine Citation:
PMID:  16407038     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: Hypospadias is a developmental anomaly of the penis and urethra that can be steroid mediated. It is characterized by a urethral opening occurring below the normal location at the tip of the penis. The link between loratadine, the active ingredient in a common over-the-counter antihistamine, and hypospadias, the most common congenital abnormality, has been the subject of controversy. We examined the effect of in utero exposure to an over-the-counter loratadine syrup on urethral development, and expression of androgen and estrogen receptors. MATERIALS AND METHODS: We orally gavaged pregnant dams with the equivalent of a daily dose of loratadine syrup, with 3 times that dose or with a corn oil gavage control from GD 12 through GD 17. Using gross and histological assessment and 3D reconstruction, we looked for urethral abnormalities in fetal GTs at E 19. We also used real-time quantitative PCR to characterize the expression levels of steroid receptor mRNA in the GT at E 19, a critical stage for completion of urethral and penile development in this species. RESULTS: Loratadine syrup disrupted normal urethral development in the mouse, based on gross morphology and histological assessment, and also disrupted steroid receptor expression, producing an expression profile similar to that resulting from in utero exposure to ethinyl estradiol. CONCLUSIONS: In utero exposure to over-the-counter loratadine syrup can result in hypospadias in this model, and creates changes in the steroid receptor mRNA expression profile similar to those elicited by a synthetic estrogen.
Authors:
Emily Willingham; Koray Agras; Marcelo Vilela; Laurence S Baskin
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  The Journal of urology     Volume:  175     ISSN:  0022-5347     ISO Abbreviation:  J. Urol.     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2006-01-12     Completed Date:  2006-02-27     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0376374     Medline TA:  J Urol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  723-6     Citation Subset:  AIM; IM    
Affiliation:
Institute for the Study and Treatment of Hypospadias, Department of Urology, School of Medicine, University of California, San Francisco, San Francisco, California 94043, USA. ewillingham@casmail.ucsf.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Histamine H1 Antagonists, Non-Sedating / adverse effects*
Loratadine / adverse effects*
Male
Mice
Penis / drug effects*,  growth & development*
Grant Support
ID/Acronym/Agency:
R01 DK058105-01/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Histamine H1 Antagonists, Non-Sedating; 79794-75-5/Loratadine
Comments/Corrections
Comment In:
J Urol. 2006 Nov;176(5):2314; author reply 2314   [PMID:  17070330 ]

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


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