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Vol. 31, Issue 5, 559-564, May 2003
Department of Pharmacology, Toxicology, and Therapeutics,
University of Kansas Medical Center, Kansas City, Kansas
Messenger RNA levels of rat organic anion transporter 1 (Oat1;
Slc22a6) and Oat2 (Slc22a7) in kidney and
Oat3 (Slc22a8) in liver are gender-predominant. Oat1 and
Oat3 are male-predominant, whereas Oat2 is female-predominant.
Gonadectomized and hypophysectomized (HX) rats were studied to
determine whether sex steroids and/or growth hormone (GH) are
responsible for these gender-divergent patterns. GH was administered to
HX rats by two daily injections (simulating male secretion) or
continuous infusion (simulating female secretion). Oat1 mRNA levels,
normally higher in male than female kidney, were lowered by gonadectomy
and HX in male rats, but not in females. Additionally, GH injections or
infusion did not alter Oat1 levels in HX rats. Oat2 mRNA levels,
typically much higher in female than in male kidney, were unaffected by gonadectomy. However, HX dramatically decreased Oat2 in female kidney
without altering male levels. GH administered by continuous infusion
increased Oat2 in kidneys of both HX male and female rats, whereas
injections had no affect. Gonadectomy reduced Oat3 mRNA levels in male
livers without affecting levels in female livers. In contrast, HX
decreased male and elevated female Oat3 mRNA. GH injections did not
significantly change Oat3 mRNA levels in HX rats, but infusion
decreased Oat3 mRNA in liver. In conclusion, androgens, but not GH, are
responsible for the Oat1 mRNA gender difference in kidney; the female
GH secretion pattern is responsible for the Oat2 mRNA gender difference
in kidney; and both androgens and the female GH secretion pattern are
responsible for the Oat3 mRNA gender difference in liver.
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