Regulation of renal oatp mrna expression by testosterone.
Lu, Run, Naoaki Kanai, Yi Bao, Allan W. Wolkoff, Victor L. Schuster.
Renal Division, Departments of Medicine, Physiology &
Biophysics; Liver Research Center; Albert Einstein College of
Medicine, Bronx, N.Y. 10461
APStracts 2:0167F, 1995.
A recently-cloned cDNA encodes "organic anion transporting
polypeptide" ("oatp"), which is expressed in rat liver
and in the kidney S3 proximal tubule. Functional characterization of
the cloned transporter indicates that estradiol 17 b D-glucuronide is
a major substrate. Because the urinary excretion of glucuronidated
steroids differs between males and females, we hypothesized that
renal oatp expression may be under sex hormone control. Total RNA was
isolated from male or female kidneys and probed with a digoxigenin
-labeled oatp antisense riboprobe. Expression of oatp mRNA expression
was quantitated by densitometry from Northern blots. Male kidneys
expressed at least six distinct oatp transcripts (4.0; 3.2; 2.9; 2.6;
1.7, and 1.2 kb). Of these, the 3.2 band was consistently the
strongest. In female rats, renal oatp mRNA expression was markedly
less, such that only the 3.2 kb was consistently detectable.
Administering testosterone to female rats increased, and
administering estradiol to male rats decreased, the steady-state
levels of renal oatp mRNA. Gonadectomized male and female rats, and
adrenalectomized male rats, were given pharmacological hormone
replacement (testosterone, estradiol, or dexamethasone, respectively)
by subcutaneous osmotic mini-pump. Castration of male rats produced a
dramatic drop in the steady-state level of all six renal oatp
transcripts. These were returned to normal by testosterone
replacement. In contrast, there was no regulation of hepatic oatp
mRNA expression by testosterone. Renal oatp mRNA expression in female
rats was mildly increased by oophorectomy. Administration of
estradiol to oophorectomized females moderately suppressed renal oatp
mRNA expression. Adrenalectomy produced a small decrease in oatp
expression, but dexamethasone replacement failed to return expression
to normal. We conclude that renal oatp mRNA expression is under
strong (stimulatory) testosterone control, and perhaps weaker
(inhibitory) estrogen control. We speculate that this regulation of
renal oatp expression is important in modulating the renal tubular
secretion of conjugated estradiol.
Received 22 February 1995; accepted in final form 21 August 1995.
APS Manuscript Number F63-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 31 October 95