| Co-Investigator(Kenkyū-buntansha) |
AONO Toshihiro Dept.Ob/Gyn.Facul.Med.Tokushima univ., 医学部, 教授 (50028445)
TOMODA Yutaka Dept.Ob/Gyn.Facul.Med.Nagoya Univ., 医学部, 教授 (60023769)
SAJI Fumitaka Dept.Ob/Gyn.Facul.Med.Osaka Uuiv., 医学部, 講師 (90093418)
FUJITA Jun Dept.Cli.Mol.Biol.Med.Kyoto Univ., 医学部, 教授 (50173430)
TAKAHASHI Michio Dept.Vet.Phys.Vet.Med.Sci.Tokyo Univ., 農学部, 教授 (30011943)
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| Research Abstract |
To clarify the role of cytokines in regulation of gonadotropin secretion, rat anterior pituitary cells were cultured with various cytokines and FSH levels in the culture supernatants were examined .Activin A showed a significant enhancement on the secretion of FSH,and mRNA for activin A was identified in rat ovarian follicles and placenta.FSH secretion was also enhanced by insulin-like growth factor.In the culture of porcine granulosa cells, IL-1, TNFalpha and IFNgamma showed a significant suppressive effect on steriodogenesis.But lymphocytes can stimulates the progesterone production by granulosa luteal cells, suggesting the complex effect of cytokines on follicular cells at different developmental stages.In the corpus luteum, macrophages inhibited 17beta-dehydroxylase activity and maintain the high local progesterone levels.During luteolysis, mRNA for cytokines of CSF and TGFbeta was detected by subtraction suggesting that these cytokines from local macrophages have a role in luteal
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cell regression.In endometrium, cytokines have important roles in the proliferation/differentiation of not only local immune cells but also endometrial cells.IL-1.and TNFalpha inhibited a process of endometrial stromal cell differentiation induced by progesterone(decidualization), and endometrial cells can produce cytokines of M-CSF,SCF,LIF,IL-6 and TGFbeta.The production of M-CSF and TGFbeta by stromal cells was regulated by gonadal steroids.In placenta, receptors for M-CSF,IL-6 and LIF were identified and the addtion of these cytokines to early pregnancy placental trophoblasts or trophoblastic cell lines showed the enhancing or inhibiting effect of these cytokines on trophoblast cell proliferation and hCG secretion.Therefore it is suggested that the cytokines produced in the uterine endometrium under the control of ovarian gonagdal steroids have roles in plascental growth and differentiation.In addition, M-CSF had growth promoting effect on pre-implantation mouse embryo.In addition to these cytokines, a novel molecule of midkine(MK)found as a product of a retinoic acid-responsive gene has an important roles in embryogenesis.The receptor for MK was analyzed and its role in placental/fetal development is intensively examined. Less
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