![[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}
|
|
|
|
|
||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Received for publication March 29, 2006.
Revised June 28, 2006.
Accepted for publication June 28, 2006.
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 (Oatps) 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 (GHRH)-receptor deficient little (lit/lit) mice, and hypophysectomized mice were utilized 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 due to male-pattern GH-secretion pattern and androgens. In kidney, gender-divergent Oatp expression is exclusively due to stimulation by androgens.
Key words:
Growth hormone, Sex hormones, Organic anion, Regulation of gene expression, Liver transporters, Regulation - transcriptional
This article has been cited by other articles:
|
|
 |
|
  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]
|
|
 |
 |
 |
|
 |
 |
 |
