Open Access

ARTICLE

MDCK cells express serotonin-regulable 11ß-hydroxysteroid dehydrogenase type 2

MARISA L. ZALLOCCHI^*1, MARIA C. DAMASCO¹, JUAN C. CALVO^1,2, CARLOS P. LANTOS¹, LAURA B. MATKOVIC¹

1 Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires and PRHOMCONICET. Buenos Aires, Argentina.
2 Instituto de Biología y Medicina Experimental (CONICET). Buenos Aires, Argentina.
* For the definition of the terms neurotransmitter and neurohormone, we adopt the terminology of David O. Norris in Vertebrate Endocrinology 3rd, Edition Academic Press. Neurotransmitter: Chemical regulators produced and secreted by neurons into synapses that produce effects on the postsynaptic and/or presynaptic cells. Neurohormones: Neural regulators that are released, like hormones, into the blood.
Address correspondence to: Dra. Laura Beatriz Matkovic’. Fax: (+54-11) 4576 3342. E-mail: lmat@qb.fcen.uba.ar

BIOCELL 2006, 30(3), 469-477. https://doi.org/10.32604/biocell.2006.30.469

Abstract

Prior to this work, we found that adrenal as well as extra-adrenal factors activate the response of renal 11ß-hydroxysteroid dehydrogenase 2 to stressful situations. These results -showing ways through which the organism hinders the pathological occupation of mineralocorticoid receptors by glucocorticoids leading to sodium retention and hypertension- prompted the present study on the nature of the above-mentioned extraadrenal factors. Serotonin was chosen because of its properties as a widely distributed neurohormone, known to interact with glucocorticoids at many sites, also exhibiting increased levels and effects under stressful situations. We studied serotonin effects on 11ß-hydroxysteroid dehydrogenase 2 activity in a cell line derived from distal nephron polarized-epithelium, employing ³H-corticosterone as substrate. The end-product, ³H-11-dehydrocorticosterone was separated from the substrate by HPLC and quantified. Serotonin stimulated 11ß-hydroxysteroid dehydrogenase 2 activity only at 2nM and 25pM, the magnitude of the response depending also on substrate concentration. The stimulation was blocked by the specific inhibitors methiothepin and ketanserin. We postulate that the organism partially prevents renal mineralocorticoid receptor occupancy by glucocorticoids, circulating at enhanced levels under stressful situations, through serotonin-mediated catabolic regulation of the 11ßhydroxysteroid dehydrogenase 2 activity. Given many, mostly positive, interactions between both hormones, this might eventually pave the way to studies on a new regulatory axis.

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