title: Pregnenolone sulfate regulates prolactin production in the rat pituitary.
abstract: Pregnenolone sulfate (PS) is a neuroactive steroid hormone produced in the brain. In this study, the effects of PS on synthesis and secretion of rat pituitary prolactin (PRL) were examined. To accomplish this, GH3 rat pituitary adenoma cells were treated with PS, which showed significantly increased mRNA and protein levels of PRL compared with the control. The mechanism of action responsible for the effects of PS on PRL synthesis and secretion was investigated by pretreating cells with inhibitors of traditional PRL- or the PS-related signaling pathway. PS-stimulated PRL transcription was significantly reduced by inhibitors of PKA, PKC and MAPK, but unchanged by GABAAR and NMDAR inhibitors. Western blotting analysis revealed that the total ERK1/2 level was upregulated in a time-dependent manner following PS treatment. An approximate 10% increase in GH3 cell proliferation was also observed in response to PS relative to the control. In the animal study, levels of PRL in the pituitary and in serum were elevated by PS. PS-stimulated PRL synthesis was also found to be associated with decreased expression of PRL target genes such as GNRH1, FSHB and LHB. These findings show that PS upregulates PRL synthesis and secretion in vivo and in vitro via MAPK signaling, suggesting that it has the potential for use as a therapeutic hormone to treat PRL-related disorders such as hypoprolactinemia and low milk supply.
authors: Department of Biomaterials ScienceCollege of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Milyang, Republic of Korea.
authors: Eun-Jin
authors: EJ
authors: Kang
authors: Department of Biomaterials ScienceCollege of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Milyang, Republic of Korea.
authors: So-Hye
authors: SH
authors: Hong
authors: Department of Biomaterials ScienceCollege of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Milyang, Republic of Korea.
authors: Jae-Eon
authors: JE
authors: Lee
authors: Department of Obstetrics and GynecologyBiomedical Research Institute, Pusan National University School of Medicine, Milyang, Republic of Korea.
authors: Seung Chul
authors: SC
authors: Kim
authors: Department of Obstetrics and GynecologyMedical College, Dongguk University, Seoul, Republic of Korea.
authors: Hoe-Saeng
authors: HS
authors: Yang
authors: Department of Bioenvironmental EnergyCollege of Natural Resources and Life Science, Pusan National University, Milyang, Republic of Korea.
authors: Pyong In
authors: PI
authors: Yi
authors: College of Environmental and Bioresource SciencesChonbuk National University, Jeonju, Republic of Korea.
authors: Sang-Myeong
authors: SM
authors: Lee
authors: Department of Biomaterials ScienceCollege of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Milyang, Republic of Korea anbs@pusan.ac.kr.
authors: Beum-Soo
authors: BS
authors: An
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism*; D011284:Pregnenolone / Q000494:pharmacology*; D011388:Prolactin / Q000097:blood / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured
chemical_list: C018370:pregnenolone sulfate; D007987:Gonadotropin-Releasing Hormone; D011284:Pregnenolone; D011388:Prolactin
keywords: neurosteroid; pituitary prolactin; pregnenolone sulfate