1996 Fiscal Year Final Research Report Summary
INTRAOVARIAN REGULATORS INVOLVED IN HUNAN FOLLICULAR GROWTH AND DISEASE
| Project/Area Number |
07457380
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | GUMMA UNIVERSITY |
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Principal Investigator |
IBUKI Yoshito Gunma Univ.Sch.Med., Dept.OB/GN., Prof., 医学部, 教授 (40008256)
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| Co-Investigator(Kenkyū-buntansha) |
ABE Yumiko Gunma Univ.Sch.Med., Dept.OB/GN., Adjunct Assist.Prof., 医学部, 教務員 (70261857)
MINEGISHI Takashi Gunma Univ.Sch.Med., Dept.OB/GN., Associate Prof., 医学部, 講師 (00209842)
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| Project Period (FY) |
1995 – 1996
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| Keywords | ovarian follicle / granulosa cell / activin / follistatin / inhibin / gonadotropin receptor / midkine |
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| Research Abstract |
The significance of intraovarian regulators in follicular growth has become increasingly recognized. Activins and follistatins were initially purified from follicular fluid as gonadal protein which modulate FSH production by the anterior pituitary gland. Recently, however much of the attention centers on their autocrine/paracrine actions in the ovary. Our study investigated the local regulatory system of their production. The production of follistatin in ovarian granulosa cell culture was stimulated by activin and FSH.Cyclic AMP and PMA induced an increase of follistatin mRNA and the involvement of both the PKA and the PKC pathways in follistatin production was suggested. Activin stimulated not only follistatin production but also the induction of the FSH receptor, and this stimulatory effect on the FSH receptor in turn was inhibited by follistatin. Therefore, it was suggested that a local regulatory system of activin in the ovarian granulosa cells exists.
Midkine is the product of a re
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tinoic acid responsive gene and it's existence in follicular fluid has been reported recently. Using the in situ hybridization technique, we proved that midkine mRNA exists exclusively in granulosa cells in the ovary. Midkine mRNA in cultured granulosa cells increased in the presence of FSH or retinoic acid. The time course analysis revealed that stimulatory effects of FSH were mimicked by 8-Br-cAMP but those of midkine were not mimicked. These results suggested that granulosa cells produce midkine under the independent control of FSH and retinoic acid.
We also reported on carbonyl reductases which were expressed in ovarian theca cells by gonadotropin injection using the subtraction hybridization technique.
Useful assay systems in the study of human follicular growth were also investigated. Human inhibin assay systems were improved and a human FSH bioassay system was established using CHO cells expressing human FSH receptors.
Our study assists in clarifying the local regulatory mechanisms in follicular growth and helps to investigate the unique diagnostic and therapeutic methods in the treatment of human ovarian disorder. Less
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