Downregulation of long-form prolactin receptor mRNA during prolactin-induced luteal regression

Abstract

Objective: Prolactin is capable of both trophic and lytic actions in rat corpora lutea. In corpora lutea responding to a trophic prolactin signal, the long form of the prolactin receptor is the dominant form and is upregulated by prolactin. We investigated whether mRNA for the short form of the prolactin receptor was dominant in corpora lutea responding to a lytic prolactin signal, and whether the relative concentrations of the mRNAs for both forms of the prolactin receptor were changed during this response. Design and methods: Immature rats were ovulated by injection of 5 IU equine chorionic gonadotrophin and 5 IU human chorionic gonadotrophin, and were hypophysectomized shortly after ovulation. Nine days after hypophysectomy, rats were injected with prolactin (500 mg/day) or vehicle for 24 (n 6, n 6) or 72 h (n 13, n 5). Total RNA was isolated from corpora lutea and mRNA for both types of prolactin receptor were analyzed by semiquantitative RT-PCR using the ribosomal protein S16 as the internal control. Results: The intensities of the long-and short-form prolactin receptor signals were normalized to the S16 internal control and expressed as relative densitometric units. The normalized values at 24 h for prolactin-treated vs vehicle-treated rats were 0.23 6 0.05 vs 0.49 6 0.15 (P > 0.05) for the short form and 4.04 6 0.8 vs 4.23 6 0.6 (P > 0.05) for the long form. The values for 72 h were 0.30 6 0.05 vs 0.24 6 0.05 (P > 0.05) for the short form and 2.76 6 0.4 vs 5.53 6 0.3 (P < 0.01) for the long form respectively. Conclusion: The long form of the prolactin receptor is the dominant form at both time-points; however, the concentration of mRNA for this receptor isoform was speci®cally downregulated by prolactin treatment. Our results suggest that the short form of the prolactin receptor alone is unlikely to mediate the luteolytic action of prolactin, but that luteolytic events may be in¯uenced via a change in the ratio of the two receptor isoforms.

Visualization of gene expression of prolactin-receptor (PRL-R) by in situ hybridization in reproductive organs of Typhlonectes compressicauda, a gymnophionan amphibian

“…Similar data showing a luteolytic effect of PRL in correlation with the degree of differentiation of luteal cells in the rat were described by Gaytan et al (2001). This regulation was dependent on the long form of PRL-R in the rat (Bowen et al 2000). In males, we have shown that mRNAs coding for the long form of PRL-R were expressed in testes, but we lack data to show any variation.…”

Lack of prolactin receptor signaling in mice results in lactotroph proliferation and prolactinomas by dopamine-dependent and -independent mechanisms

“…This is similar to other models of chronic hyperprolactinemia in which there is loss of the normal response of tuberoinfundibular dopaminergic neurons to PRL (39). Indeed, there is evidence that in other tissues PRL regulates its own receptor, with downregulation observed at extremely high concentrations, although there does not appear to be a consistent PRL level at which this downregulation occurs (41)(42)(43). The dichotomous response we observed appeared to occur with preceding serum PRL levels of approximately 500 ng/ml or greater.…”

Colocalization of GH, TSH and prolactin, but not ACTH, with ?LH-immunoreactivity: evidence for pluripotential cells in the ovine pituitary

“…Furthermore, at the time of the preovulatory LH surge, a simultaneous surge in prolactin occurs in many species (Djahanbakhch et al 1984;Arbogast and Ben-Jonathan 1988;Campbell et al 1990;Anderson et al 2001;Skinner and Caraty 2003). In the rat, this preovulatory prolactin surge has been implicated in causing full regression of the preceding corpus luteum (Bowen and Keyes 1999;Bowen et al 2000) but its physiological role remains unknown in other species. It is tempting to speculate that this subpopulation of prolactin expressing gonadotropes may also be responsible to the preovulatory rise in prolactin.…”