Endocrine regulation of gender-divergent mouse organic anion-transporting polypeptide (Oatp) expression. 2006

Xingguo Cheng, and Jonathan Maher, and Hong Lu, and Curtis D Klaassen
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, KS 66160, USA.

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.

UI MeSH Term Description Entries
D007016 Hypophysectomy Surgical removal or destruction of the hypophysis, or pituitary gland. (Dorland, 28th ed) Hypophysectomies
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D004702 Endocrine Glands Ductless glands that secrete HORMONES directly into the BLOOD CIRCULATION. These hormones influence the METABOLISM and other functions of cells in the body. Endocrine Gland,Gland, Endocrine
D004967 Estrogens Compounds that interact with ESTROGEN RECEPTORS in target tissues to bring about the effects similar to those of ESTRADIOL. Estrogens stimulate the female reproductive organs, and the development of secondary female SEX CHARACTERISTICS. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Estrogen,Estrogen Effect,Estrogen Effects,Estrogen Receptor Agonists,Estrogenic Agents,Estrogenic Compounds,Estrogenic Effect,Estrogenic Effects,Agents, Estrogenic,Agonists, Estrogen Receptor,Compounds, Estrogenic,Effects, Estrogen,Effects, Estrogenic,Receptor Agonists, Estrogen
D005260 Female Females
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression

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