GPR30 Differentially Regulates Short Latency Responses of Luteinising Hormone and Prolactin Secretion to Oestradiol

Rapid, nongenomic actions of 17 beta-oestradiol (E(2)) on hypothalamic neurones that may be relevant to reproductive function were described decades ago. The orphan G protein-coupled receptor, GPR30, was recently shown to bind oestrogens and to trigger rapid signalling in vitro, and is expressed in several rat and human brain regions, including the hypothalamus. We used two complementary approaches to investigate the role of GPR30 in hypothalamic responses to E(2) that are relevant to reproductive physiology. Serial blood sampling after the acute administration of the selective GPR30 agonist G1 was used to assess the role of GPR30 in short latency negative-feedback inhibition of luteinising hormone (LH) secretion and facilitation of prolactin secretion in ovariohysterectomised female rats. In vivo RNA interference (RNAi), mediated by adeno-associated virus-expressing small hairpin RNA (shRNA) infused into the mediobasal hypothalamus, was used to study the effects of GPR30 knockdown on these rapid responses to E(2). Longer-term actions of E(2) on female sexual behaviour (lordosis) were also examined in female rats subjected to in vivo RNAi. Administration of E(2) or G1 triggered a short latency surge of prolactin secretion, and animals subjected to GPR30 RNAi showed significantly less E(2)-dependent prolactin release than animals receiving control virus. G1 did not mimic E(2) negative-feedback inhibition of LH secretion, and GPR30 RNAi did not interfere with E(2) suppression of LH or facilitation of lordosis behaviour. These findings suggest that activation of GPR30 promotes short latency prolactin secretion but does not mediate E(2) negative-feedback inhibition of LH secretion or E(2) facilitation of female reproductive behaviour.