Different expression of the two dopaminergic D2 receptors, D2415 and D2444, in two types of lactotroph each characterised by their response to dopamine, and modification of expression by sex steroids.

Dopamine inhibits prolactin liberation acting via the D2 type receptor. Two different electrophysiological responses to dopamine have been shown to characterise two types of lactotroph isolated from the lactating female rat. It is now known that differential splicing of the pre-messenger RNA coding for the D2 receptor leads to the production of two D2 subtypes, D2(415) and D2(444). These subtypes differ in the region which is believed to be responsible for the binding of G proteins, and could thus lead to the activation of different intracellular second messenger systems. Here we show that the pre-messenger RNA for the D2 receptor is differentially spliced in such a way that the ratio D2(415)/D2(444) is significantly different (2.91 +/- 0.6 vs 1.29 +/- 0.14) between two populations of lactotrophs, each enriched in cells showing one type of response to DA. We further show that the ratio D2(415)/D2(444) can be changed by treatment of prolactin cells in primary culture with progesterone or testosterone. Estrogen did not change the ratio, but diminished the total amount of D2 cDNA. Regulation of differential splicing by sex steroids could provide a mechanism for modifying lactotroph responsiveness to DA in different physiological situations.