Endocrinology, Vol 134, 1263-1268, Copyright © 1994 by Endocrine Society

ARTICLES

Evidence that stimulatory dopamine receptors may be involved in the regulation of prolactin secretion

TE Porter, D Grandy, J Bunzow, CD Wiles, O Civelli and LS Frawley
Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston 29425.

It is well established that dopamine (DA) effectively inhibits PRL secretion from anterior pituitary mammotropes via D2-DA receptors. Paradoxically, it is reported that the monoamine can actually increase PRL release under appropriate experimental conditions. Although the mechanism underlying this stimulatory effect remains undefined, the ability of D1- and D5-DA receptors to activate adenylyl cyclase raises the possibility that a similar receptor subtype is present in the anterior pituitary and mediates the stimulatory effects of DA on PRL release. The purpose of the present study was to explore this possibility. First, we tested whether D1 and D5 receptors could couple to and stimulate PRL secretion. Subclones of GH4C1 cells (which secrete PRL, but do not express DA receptors) stably expressing human D1 or D5 receptors were treated with DA (10(-16)-10(-6) M), and the medium PRL content was measured by RIA. Subclones transfected with short or long forms of the human D2 receptor were also tested. As expected, DA (10(- 6) M) inhibited PRL release from cells expressing either short or long D2 receptors by 41% and 39%, respectively (P < 0.01; n = 4 separate experiments). In contrast, comparable concentrations of DA (10(-(8) and 10(-6) M) increased PRL release from cells expressing D1 or D5 receptors by 76% and 122%, respectively (P < 0.01; n = 4). Thus, both D1 and D5 receptors were fully capable of stimulating PRL release from transfected GH4C1 cells. We next sought to determine whether the gene for at least one of these structurally similar receptors was expressed in rat anterior pituitary tissue. First strand cDNA was synthesized, using a rat D5-specific oligonucleotide primer and reverse transcriptase, from total RNA extracted from the anterior pituitary glands of five lactating female rats. The specifically primed cDNA then served as a template for 35 cycles of polymerase chain reaction amplification in which nested primers specific for the rat D5 receptor were used. Electrophoresis of the DNA resolved a 696-basepair band corresponding to a fragment of the D5 receptor in each of five anterior pituitary samples (verified by digestion with three different restriction endonucleases). Taken together, these results demonstrate that both D1 and D5 receptors are capable of mediating the stimulatory effects of DA on PRL release and that the mRNA for DA D5 receptors is present in rat anterior pituitary glands. Our findings support the view that PRL release in vivo may be modulated via one or more stimulatory DA receptors.

This article has been cited by other articles:

				N. Ben-Jonathan and R. Hnasko Dopamine as a Prolactin (PRL) Inhibitor Endocr. Rev., December 1, 2001; 22(6): 724 - 763. [Abstract] [Full Text] [PDF]

				S. A. Schnell, S. You, and M. E. El Halawani D1 and D2 Dopamine Receptor Messenger Ribonucleic Acid in Brain and Pituitary during the Reproductive Cycle of the Turkey Hen Biol Reprod, June 1, 1999; 60(6): 1378 - 1383. [Abstract] [Full Text]

				S. Sanyal and H. H. M. Van Tol Dopamine D4 Receptor-Mediated Inhibition of Cyclic Adenosine 3',5'-Monophosphate Production Does Not Affect Prolactin Regulation Endocrinology, May 1, 1997; 138(5): 1871 - 1878. [Abstract] [Full Text] [PDF]