Regulatory Peptides, 45 (1993) 31-35 31 © 1993 Elsevier Science Publishers B.V. All rights reserved 0167-0115/93/$06.00 REGPEP 01349 Transactivation of the rat oxytocin and vasopressin promoters by nuclear hormone receptors J. Peter H. Burbach, Roger A.H. Adan, Joke J. Cox and Sofia Lopes da Silva Rudolf Magnus Institute, Department of Pharmacology, Utrecht University, Utrecht(The Netherlands) Key words: Steroid hormone; Thyroid hormone; Retinoic acid; Estrogen; Gene regulation; Hormone response element Introduction The regulation of the oxytocin (OT) and vaso- pressin (VP) genes in the magnocellular neurons of the supraoptic (SON) and paraventricular nuclei (PVN) displays remarkable parallels. For instance, the levels of OT mRNA and VP mRNA increase similarly during postnatal development, hyperosmo- lality, pregnancy and lactation [ 1]. It is believed that the similarity in responsiveness resides in either com- mon regulatory elements in the genes or in common neural or hormonal inputs of the OT and VP neurons [2]. Although there is no significant overall homol- ogy between the 5'-flanking regions of the OT and VP genes, both genes contain a number of TGACC motifs [3]. Such sequences are often part of response elements of nuclear hormone receptors. Steroid hor- mones have been implicated in the regulation of OT and VP systems [4]. We here summarize the results of experiments aimed to determine and compare the responsiveness of OT and VP genes to members of the steroid/thyroid hormone receptor superfamily. Correspondence to: J.P.H. Burbach, Rudolf Magnus Institute, De- partment of Pharmacology, Utrecht University, Vondellaan 6, 3521 GD Utrecht, The Netherlands. Transactivation Since cultured cells with abundant expression of the OT gene or VP gene are not available experi- ments were performed in heterologous expression systems, i.e., tumor cell lines without endogenous OT or VP gene expression that were transfected with OT or VP promoter-reporter gene constructs. Two types of cell lines were used: cell lines with endogenous hormone receptors, e.g., MCF-7 breast tumor cells containing the estrogen receptor (ER) and thyroid hormone receptors (TR) and P 19 embryocarcinoma (EC) cells containing retinoic acid receptors (RAR) and retinoid X receptors (RXR), or cell lines co- transfected with plasmids expressing nuclear hor- mone receptors. The activity of the rat OT promoter (nucleotides -361 to + 16) was stimulated by the ligand-activated ER, TR~ and RAR~ and/~ [5-7]. The human OT promoter was similarly responsive to these hormone receptors [6-9]. In P19 EC cells the response to estrogens was by far the strongest (approx. 200-300 fold) and to thyroid hormone the weakest (approx. 10-fold) when using the -361 tot + 16 region of the rat OT gene coupled to luciferase (pROLUC). The stimulation was about 10-fold when the endogenous