Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2006) 11 S49

ECE2006 Symposia How hormones get into cells (4 abstracts)

Cell surface carrier - mediated transport of steroid hormones

J Steffgen , Y Hagos , A Asif , E Beéry & G Burckhardt


Abt. Vegetative Physiologie und Pathophysiologie, Universität Göttingen, Göttingen, Germany.


Experimental data demonstrate interactions of steroids with efflux carriers of the multidrug-resistance transporter family (P-glycoprotein, MRP) as well as the poly-specific uptake carriers of the organic anion transporting polypetptide (OATP), organic cation transporter (OCT), and the organic anion transporter (OAT) families in different tissues.

P-glycoprotein is associated with glucocorticoid-resistance of many diseases including cancer but also modulates androgen responsiveness in prostate cancer cells. Transport of conjugated steroid hormones like estradiol-17ß-glucuronide or estrone sulfate and DHEAS by OATPs has been demonstrated in placenta, mammary gland, keratinocytes, small intestinal epithelial cells and hepatocytes. Estrone sulfate and DHEAS also interact with OATs in renal proximal tubule cells and placenta. Cortisol transport by OATs has been shown in kidney, placenta, and the blood–brain barrier. In rat adrenal cortex, in situ hybridization localized OAT1 to the outer zona fasciculata, OATP3 to the zona glomerulosa, OATP1 and OATP2 to the inner zona fasciculata and outer zona reticularis and OCT2 to the zona glomerulosa and outer zona fasciculata. RT-PCR detected OAT3 and OAT4 mRNAs in human adrenal tissue and the human adrenal cell line NCI-H295R. When human OAT3 and OAT4 were expressed in Xenopus laevis oocytes, only hOAT3 showed [3H]cortisol uptake (apparent Kt=2.4 μM). Uptake of the OAT-substrate [3H]PAH (p-aminohippurate) into NCI-H295R cells was trans-stimulated in cells preloaded with unlabeled PAH, glutarate, and cortisol. This trans-stimulation indicates PAH/PAH, PAH/glutarate, and, most important, PAH/cortisol exchange through OAT3. Glutarate and cortisol in the medium cis-inhibited, i.e. competed with, [3H]PAH uptake, further documenting the interaction of cortisol with OAT3. Finally, glutarate in the medium trans-stimulated cortisol release, indicating glutarate-driven efflux of cortisol. These experiments support the concept of anion exchanger(s) contributing not only to uptake of steroids into cells but also, at least in part, to the secretion from adrenocortical cells.

Volume 11

8th European Congress of Endocrinology incorporating the British Endocrine Societies

European Society of Endocrinology 
British Endocrine Societies 

Browse other volumes

Article tools

My recent searches

No recent searches.