title: Prolonged stimulation with thyrotropin-releasing hormone and pituitary adenylate cyclase-activating polypeptide desensitize their receptor functions in prolactin-producing GH3 cells.
abstract: We used somatolactotroph GH3 cells to examine changes in response to stimulation with thyrotropin-releasing hormone (TRH) and pituitary adenylate cyclase-activating polypeptide (PACAP) after sustained treatment with these peptides. TRH and PACAP increased prolactin promoter activity in mock- and PACAP type 1 receptor (PAC1R)-transfected cells. When the cells were pretreated with TRH for 48 h, the response of the prolactin promoter to both TRH and PACAP was diminished. Similarly, in PAC1R-transfected GH3 cells pretreated with PACAP, the effects of TRH and PACAP on the prolactin promoter were eliminated. The stimulation of prolactin mRNA expression by TRH and PACAP was eliminated by prolonged pretreatment with these peptides in PAC1R-transfected cells. Both the serum response element (SRE) promoters and cAMP response element (CRE) promoters were activated by TRH and PACAP in either mock- or PAC1R-transfected cells. Pretreatment for 48 h with TRH also eliminated the effects of TRH and PACAP on the SRE and CRE promoters, and pretreatment of PAC1R-transfected cells with PACAP for 48 h reduced the responses of the SRE and CRE promoters to TRH and PACAP. These observations demonstrated that sustained stimulation with TRH and PACAP desensitizes their own and each other's receptors.
authors.affiliation: Department of Obstetrics and Gynecology, Shimane University, School of Medicine, Izumo 693-8501, Japan.
authors.forename: Tselmeg
authors.initials: T
authors.lastname: Mijiddorj
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Kanasaki
authors.forename: Sukhbaatar
authors.initials: S
authors.lastname: Unurjargal
authors.forename: Aki
authors.initials: A
authors.lastname: Oride
authors.forename: Indri
authors.initials: I
authors.lastname: Purwana
authors.forename: Kohji
authors.initials: K
authors.lastname: Miyazaki
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D049410:Luciferases, Renilla / Q000096:biosynthesis / Q000235:genetics; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000502:physiology*; D010903:Pituitary Gland, Anterior / Q000166:cytology; D061251:Primary Cell Culture; D011388:Prolactin / Q000096:biosynthesis* / Q000235:genetics; D011401:Promoter Regions, Genetic; D051381:Rats; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / Q000235:genetics* / Q000378:metabolism; D018025:Receptors, Thyrotropin-Releasing Hormone / Q000235:genetics* / Q000378:metabolism; D027602:Serum Response Element; D013973:Thyrotropin-Releasing Hormone / Q000502:physiology*
chemical_list: D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D018025:Receptors, Thyrotropin-Releasing Hormone; D013973:Thyrotropin-Releasing Hormone; D011388:Prolactin; D049410:Luciferases, Renilla