NCBI Summary:
This gene encodes the D2 subtype of the dopamine receptor. This G-protein coupled receptor inhibits adenylyl cyclase activity. A missense mutation in this gene causes myoclonus dystonia; other mutations have been associated with schizophrenia. Alternative splicing of this gene results in two transcript variants encoding different isoforms. A third variant has been described, but it has not been determined whether this form is normal or due to aberrant splicing. [provided by RefSeq]
General function
Receptor
Comment
Cellular localization
Plasma membrane
Comment
Ovarian function
Follicle rupture
Comment
Dopamine receptor 2 activation inhibits ovarian vascular endothelial growth factor secretion invitro: implications for treatment of ovarian hyperstimulation syndrome with dopamine receptor 2 agonists. Ferrero H 2014 et al.
OBJECTIVE
To ascertain whether vascular endothelial growth factor (VEGF) secretion by luteinized granulosa cells (GCs) is modulated by the dopaminergic system in a dose-dependent fashion and how this is related to the differential efficacy of dopamine receptor 2 (D2)-agonists (D2-ag) in preventing ovarian hyperstimulation syndrome (OHSS).
DESIGN
The relationship between the dopaminergic system and VEGF secretion in luteinized GCs was evaluated. Archived human ovaries were immunostained to characterize D2 expression.
SETTING
University affiliated infertility center.
PATIENT(S)
Premenopausal women and egg donors.
INTERVENTION(S)
Luteinized GCs were cultured with the D2-ag cabergoline. Human ovarian sections were immunostained for D2.
MAIN OUTCOME MEASURE(S)
The VEGF was measured by ELISA and D2 expression was evaluated by In-Cell ELISA. The D2 expression throughout the luteal phase was characterized by immunohistochemistry.
RESULT(S)
The VEGF secretion was decreased by the D2-ag in a dose-dependent fashion. The efficiency of this process was correlated with the amount of D2 expressed by luteinized GCs. A decrease in D2 expression in ovarian sections was observed during the late luteal phase.
CONCLUSION(S)
The efficacy of D2-ags in preventing OHSS might rely on their capacity to inhibit VEGF secretion by luteinized GCs. Because this capacity is dose-dependent, increasing the intraovarian concentration of D2-ags should be explored as a means of increasing the efficacy of these drugs in preventing OHSS.
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Expression regulated by
Comment
Ovarian localization
Granulosa, Theca, Luteal cells
Comment
Evidences for the Existence of a Low Dopaminergic Tone in Polycystic Ovarian Syndrome: Implications for OHSS Development and Treatment. G? R et al. Context: The dopamine/dopamine receptor 2 (D2/Drd2) pathway modulates vascular endothelial growth factor (VEGF)-dependent vascular permeability and angiogenesis in the ovary. Deregulation of the VEGF/VEGF receptor (VEGFR)-2 pathway leading to increased risk of ovarian hyperstimulation syndrome has been described in the ovary of patients suffering from polycystic ovarian syndrome (PCOS). Objective: The objective of the study was to ascertain whether deregulation of the VEGF/VEGFR-2 might a least be partially due to abnormalities of the D2/Drd2 pathway in PCOS women. Design: Dated, archived ovaries from PCOs and control group patients as well as human chorionic gonadotropin-stimulated luteinized granulosa cells form PCOS and non-PCOS oocyte patients were used. Setting: The study was conducted at a private research center. Patients or Other Participants: PCOS and nonpolycystic ovarian patients and oocyte patients participated in the study. Intervention(s): Human ovarian sections were stained against the Drd2 antibody. Human chorionic gonadotropin-stimulated luteinized granulosa cells (LGC) were cultured in the presence/absence and the Drd2 agonist cabergoline. Main Outcome Measure(s): Drd2 and vascularized stained area in the theca layer of antral (<8 mm) and luteinized follicles was quantified. VEGF, D2, and its related metabolites were measured in the supernatant of cultured LGC by ELISA and HPLC, respectively. VEGFR-2 and Drd2 expressed by LGC was quantified through an In-Cell ELISA. Results: Decreased Drd2 expression and increased vascularization in the theca layer of antral and luteinized follicles of PCOS ovaries was observed. A lower dopamine production and reduced efficacy of cabergoline in inhibiting VEGF secretion was uncovered in LGC from PCOS. Conclusions: Decreased dopaminergic tone as well as deregulated Drd2 signaling might explain higher VEGF and vascularization leading to increased ovarian hyperstimulation syndrome risk in PCOS.
Dopamine receptors in equine ovarian tissues King SS, et al .
Dopamine (DA) agonist and antagonist treatments can affect ovarian reproductive events in the mare. To support our theory that DA produces these effects by acting directly on the ovary, we analyzed equine ovarian tissues for the presence of dopamine receptor-1 (D1r) and dopamine receptor-2 (D2r) mRNA by reverse transcription polymerase chain reaction (RT-PCR) and D1r and D2r proteins by Western blot and immunohistochemistry (IHC). RT-PCR was performed on RNA isolated from ovarian cortex, medulla, granulosa/theca or corpus luteum (CL) tissues and from pituitary (D2r control) and renal artery (D1r control). D1r and D2r specific primers were designed from partial DNA sequences known for the horse (D2r) or conserved sequences from other species (D1r). Western blot analyses were conducted on CL, cortex and granulosa/theca samples and IHC was performed on CL tissues using D1r or D2r specific antibodies. The incidence of positive D2r mRNA was high in CL and ovarian cortex, low in granulosa/theca, and not detectable in ovarian medulla. Dopamine D1r mRNA incidence was high (50%) only in CL tissues. D1r and D2r antibody staining was positive for each tissue type analyzed by Western blot procedures. All CL tissues prepared by IHC showed positive staining for D1r and D2r proteins. Both DA receptor proteins appeared uniformly distributed throughout the CL tissue. These results indicate that equine ovarian tissues do possess D1r and D2r, and suggests that DA can act directly on ovarian tissues through its interaction with DA receptors.