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      Decreased Expression of the Two D 2 Dopamine Receptor Isoforms in Bromocriptine-Resistant Prolactinomas

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          Bromocriptine or other dopamine agonists are usually effective for the treatment of prolactin-secreting adenomas. Five to 18% of prolactinomas, however, do not respond to such therapy. We have shown previously that such resistance to bromocriptine correlates with reduced binding to the D<sub>2</sub> receptor subtype of dopamine, the major PRL inhibiting factor. In the present work, we demonstrated that reduced binding actually corresponds to decreased expression of the gene coding for the D<sub>2</sub> receptor in the pituitary from bromocriptine-resistant patients, as shown by 4-fold lower levels of the corresponding mRNAs compared to those coding for actin. The existence of two D<sub>2</sub> receptor isoforms, D<sub>2</sub>S and D<sub>2</sub>L generated by alternative splicing, has been described in several tissues, including the pituitary. Both are negatively coupled to adenylyl cyclase and inhibit prolactin secretion, but, in addition, the shortest one (D<sub>2</sub>S) is more efficiently coupled to phospholipase C. Consequently, we also investigated whether expression of a particular D<sub>2</sub> receptor isoform was preferentially affected in resistant adenomas. The proportion of messengers corresponding to the short receptor isoform (D<sub>2</sub>S) was lower in resistant compared to responsive adenomas: D<sub>2</sub>S/D<sub>2</sub>L = 0.74 ± 0.08 and 1.00 ± 0.07, respectively. In parallel, much lower levels of D<sub>2</sub> receptor mRNAs were found in growth hormone-secreting adenomas, with a D<sub>2</sub>S/D<sub>2</sub>L ratio comparable to those of both normal human pituitary and bromocriptine-sensitive prolactinomas (1.05 ± 0.11). Thus, resistance to bromocriptine therapy seems to involve defects in D<sub>2</sub> dopamine receptor expression and possibly in posttranscriptional splicing.

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          Author and article information

          S. Karger AG
          09 April 2008
          : 60
          : 3
          : 314-322
          aICNE, UMR 9941 CNRS, Université Aix-Marseille II, Faculté de Médecine Nord, Marseille, bINSERM U159, Centre Paul-Broca, cINSERM U332, ICGM, Paris, dService Endocrinologie et Diabétologie, Lille, France
          126764 Neuroendocrinology 1994;60:314–322
          © 1994 S. Karger AG, Basel

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          Page count
          Pages: 9
          Gonadotropins and Prolactin


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