| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1994: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1993: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1992: ¥600,000 (Direct Cost: ¥600,000)
|
|---|
| Research Abstract |
In granulosa cells, Gn-RH stimulated [^<32>P] phosphate incorporation into phosphatidylinositol (PtdIns) , which could be terminated by displacement of previously boundGn-RH from its receptor by antide and restarted by reoccupyingthe receptors with G1n-RH.Antide could rapidly prevent Gn-RH-stimulated PtdIns phosphorylation whenever it was added to incubations. An identical effect of antide was observed also in the anti-FSH action of Gn-RH.The aromatase activity initiated by FSH was quenched by Gn-RH and restarted at a time when Gn-RH was removed from its receptor by antide. These two responses associated with the occupancy of Gn-RH receptor provide the evidence in favor of a tight coupling of stimulated PtdIns turnover to suppression of aromatase activation. Taken together these data of requirement of continued occupancy of receptor for Gn-RH to exert its action, Gn-RH or Gn-RH-like hormonein ovaries, in addition to from pituitary, could participate in the control of steroidogenesis in
… More
the ovary in an autocrine or a paracrine manner.
In human ovarian carcinomas surgically removed and human ovarian carcinoma cell lines, Gn-RH was shown to be present in extracts of ovarian mucinouscystadenocarcinoma sample (0.8<plus-minus>0.12pg/mgprotein) and ovarian adenocarcinoma cell line SK-OV-3 (0.92<plus-minus>0.17 pg/mgprotein) , but not in the normal ovary and placenta. Two of two extract samples from individual cases evoked dose-dependent phosphoinositide breakdown in rat granulosa cells similar to that caused by authentic Gn-RH.Gn-RH mRNA was detected in two of two mucinouscystadenocarcinoma specimens, one of one serouscystadenocarcinoma, and SK-OV-3cells, but not in the dysgerminoma, mucinouscystadenoma, and normal ovary and placenta. High affinity binding sites with nonomolar range of Kd and Gn-RHR mRNA were detected in a high proportion (over 90%) of the specimens from endometria (6 of 6) and endometrial carcinomas (16 of 17) , myometria (6 of 6) and myomas (4 of 5) , epithelial carcinoma (21 of 23) and stromal tumors (3 of 3) of the ovary. There was no substantial Gn-RHR in cervical carcinomas or germ cell-drived tumors of the ovary. Cloned cell lines gave identical results to those obtained in their respective mother tum
We detected Gn-RHR in a wide range of the carcinomas and tissues originating from the endometrium and ovary, but not in the uterine cervix or germ cell-derived tumors. The expression of Gn-RH receptor raises the possibility that Gn-RH may play a direct regulatory role in the growth of these carcinomas, and provides a possible point of attack for therapeutic approaches using Gn-RH analogs in these malignancies. The demonstration of Gn-RH and its mRNA raises the possibility that Gn-RH may play an autocrine regulatory role in the growth of ovarian carcinoma. Less
|
