title: Tokishakuyakusan directly attenuates PACAP's luteolytic action on luteal function in the rat ovary.
abstract: We investigated the potential direct effects of Tokishakuyakusan (TS) on progestin [progesterone and 20alpha-hydroxyprogesterone (20alpha-OH-P)] and cyclic adenosine-3',5'-monophosphate (cAMP) production in cultured rat luteal cells. In addition, we examined whether TS regulates the inhibitory effects of pituitary adenylate cyclase-activating polypeptide (PACAP), a newly found peptide, on luteinizing hormone (LH)-stimulated progesterone production. TS significantly stimulated progesterone, but not 20alpha-OH-P, production and cAMP accumulation through 24 hours of culture. PACAP-38 significantly elevated progesterone, 20alpha-OH-P and cAMP levels at all concentrations studied. On the other hand, PACAP-38 inhibited the production of progesterone and the accumulation of cAMP enhanced by LH, while the ratio of progesterone to 20alpha-OH-P was significantly decreased by PACAP-38 + LH. Concomitant treatment with TS and PACAP-38 + LH increased the ratio of progesterone to 20alpha-OH-P more than with PACAP-38 + LH. The present data have demonstrated that TS stimulates progesterone production in rat luteal cells, reconfirming our previous evidence that TS stimulates luteal steroidogenesis. The data further suggest that TS tends to attenuate PACAP's inhibition of LH-stimulated progesterone production, suggesting a luteotrophic effect within the corpus luteum.
authors.affiliation: Department of Obstetrics and Gynecology, Institute of Clinical Medicine, School of Medicine, Cluster of Medical Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8575, Japan. usukisa@skyblue.ocn.ne.jp
authors.forename: Satoshi
authors.initials: S
authors.lastname: Usuki
authors.forename: Eri
authors.initials: E
authors.lastname: Kotani
mesh_terms: D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006064:Gonadotropins, Equine / Q000494:pharmacology; D006736:Horses; D006801:Humans; D008184:Luteal Cells / Q000187:drug effects / Q000378:metabolism; D007986:Luteinizing Hormone / Q000494:pharmacology; D008186:Luteolytic Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D009479:Neuropeptides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D010053:Ovary / Q000187:drug effects*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011374:Progesterone / Q000096:biosynthesis; D011372:Progestins / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar
chemical_list: C495401:ADCYAP1 protein, human; C495403:Adcyap1 protein, rat; D006063:Chorionic Gonadotropin; D004365:Drugs, Chinese Herbal; D006064:Gonadotropins, Equine; D008186:Luteolytic Agents; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011372:Progestins; C413220:toki-shakuyaku-san; D011374:Progesterone; D007986:Luteinizing Hormone; D000242:Cyclic AMP