![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas
Several examples of gender-divergent pharmacokinetics exist in humans and experimental animals, and one reason for these variations may be gender differences in transporter expression. Organic anion transporting polypeptides (Oatp) are transporters involved in hepatic and renal uptake of many organic compounds. In mouse livers, Oatp1a1 is male-predominant, whereas Oatp1a4 is female-predominant. However, in kidneys, Oatp1a1 and Oatp3a1 are both female-predominant. The purpose of the present study was to determine whether sex hormones and/or growth hormone (GH) secretion patterns are responsible for the gender-specific Oatp expression in mice. Gonadectomized mice, GH-releasing hormone receptor-deficient little (lit/lit) mice, and hypophysectomized mice were used with replacement of sex hormones or GH in male or female secretion patterns. Androgens increased Oatp1a1 mRNA in liver and kidney, whereas male-pattern GH administration increased Oatp1a1 mRNA in livers but not in kidneys. Hepatic Oatp1a4 mRNA levels were decreased by both androgens and male-pattern GH administration. In kidneys, Oatp3a1 mRNA expression was only induced by androgen treatment. In conclusion, gender-divergent Oatp expression in liver is caused by male-pattern GH secretion pattern and androgens. In kidney, gender-divergent Oatp expression is exclusively caused by stimulation by androgens.
Address correspondence to: Dr. Curtis D. Klaassen, Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, KS 66160. E-mail: cklaasse{at}kumc.edu
This article has been cited by other articles:
|
|
 |
|
  T. Kano, Y. Kato, K. Ito, T. Ogihara, Y. Kubo, and A. Tsuji Carnitine/Organic Cation Transporter OCTN2 (Slc22a5) Is Responsible for Renal Secretion of Cephaloridine in Mice Drug Metab. Dispos., May 1, 2009; 37(5): 1009 - 1016. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Fan, G.-Y. Tao, G. Wang, Y. Chen, W. Zhang, Y.-J. He, Q. Li, H.-P. Lei, F. Jiang, D.-L. Hu, et al. Effects of Ginkgo biloba Extract Ingestion on the Pharmacokinetics of Talinolol in Healthy Chinese Volunteers Ann. Pharmacother., May 1, 2009; 43(5): 944 - 949. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. B. Buckley and C. D. Klaassen Mechanism of Gender-Divergent UDP-Glucuronosyltransferase mRNA Expression in Mouse Liver and Kidney Drug Metab. Dispos., April 1, 2009; 37(4): 834 - 840. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. J. Cui, X. Cheng, Y. M. Weaver, and C. D. Klaassen Tissue Distribution, Gender-Divergent Expression, Ontogeny, and Chemical Induction of Multidrug Resistance Transporter Genes (Mdr1a, Mdr1b, Mdr2) in Mice Drug Metab. Dispos., January 1, 2009; 37(1): 203 - 210. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Cheng and C. D. Klaassen Critical Role of PPAR-{alpha} in Perfluorooctanoic Acid- and Perfluorodecanoic Acid-Induced Downregulation of Oatp Uptake Transporters in Mouse Livers Toxicol. Sci., November 1, 2008; 106(1): 37 - 45. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. R. Knight, S. Choudhuri, and C. D. Klaassen Constitutive mRNA Expression of Various Glutathione S-Transferase Isoforms in Different Tissues of Mice Toxicol. Sci., December 1, 2007; 100(2): 513 - 524. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. L. VanWert, R. M. Bailey, and D. H. Sweet Organic anion transporter 3 (Oat3/Slc22a8) knockout mice exhibit altered clearance and distribution of penicillin G Am J Physiol Renal Physiol, October 1, 2007; 293(4): F1332 - F1341. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
