DIF-1, an anti-tumor substance found in Dictyostelium discoideum, inhibits progesterone-induced oocyte maturation in Xenopus laevis.
Differentiation-inducing factor-1 (DIF-1; 1-(3,5-dichloro-2,6-dihydroxy-4-methoxyphenyl)hexan-1-one) is a putative morphogen that induces stalk-cell formation in the cellular slime mold Dictyostelium discoideum. DIF-1 has previously been shown to suppress cell growth in mammalian cells. In this study, we examined the effects of DIF-1 on the progesterone-induced germinal vesicle breakdown in Xenopus laevis, which is thought to be mediated by a decrease in intracellular cAMP and the subsequent activation of mitogen-activated protein kinase (MAPK) and maturation-promoting factor, a complex of cdc2 and cyclin B, which regulates germinal vesicle breakdown. DIF-1 at 10-40 microM inhibited progesterone-induced germinal vesicle breakdown in de-folliculated oocytes in a dose-dependent manner. Progesterone-induced cdc2 activation, MAPK activation, and c-Mos accumulation were inhibited by DIF-1. Furthermore, DIF-1 was found to inhibit the progesterone-induced cAMP decrease in the oocytes. These results indicate that DIF-1 inhibits progesterone-induced germinal vesicle breakdown possibly by blocking the progesterone-induced decrease in [cAMP](i) and the subsequent events in Xenopus oocytes.
Kubohara
Yuzuru
Y
Biosignal Research Center, Institute for Molecular and Cellular Regulation (IMCR), Gunma University, Showa-machi 3-39-15, Maebashi 371-8512 , Japan. kubohara@showa.gunma-u.ac.jp
Hanaoka
Yoichi
Y
Akaishi
Emi
E
Kobayashi
Hisae
H
Maeda
Mineko
M
Hosaka
Kohei
K
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D004023:Dictyostelium / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006588:Hexanones / Q000737:chemistry / Q000494:pharmacology*; D016200:Maturation-Promoting Factor / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009865:Oocytes / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology*; D017231:Proto-Oncogene Proteins c-mos / Q000378:metabolism; D014982:Xenopus laevis
D006588:Hexanones; C053433:1-((3,5-dichloro)-2,6-dihydroxy-4-methoxyphenyl)-1-hexanone; D011374:Progesterone; D000242:Cyclic AMP; D017231:Proto-Oncogene Proteins c-mos; D016200:Maturation-Promoting Factor; D020928:Mitogen-Activated Protein Kinases