| Budget Amount *help |
¥12,700,000 (Direct Cost: ¥12,700,000)
Fiscal Year 2002: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2001: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2000: ¥5,700,000 (Direct Cost: ¥5,700,000)
|
|---|
| Research Abstract |
Our study was focused on the clarification of molecular mechanism for the production of gonadotropin(subunits) in the human FSH secreting pituitary adenomas and in the human non-functioning pituitary adenomas. A cell line HP75 which was originally derived from the non-functioning human pituitary adenoma was also studied. By RTPCR and immunohistochemistry(IHC) , we studied hormonal expression(GH, PR, TSH, ACTH , FSH β SU, LHβSU, and αSU) and transcription factors(Lhx3, Prop-1, Ptxl, Pit-1, GATA-2, SF-1, DAX1, NeuroDl, Tpit). We also studied co-factors including receptors such as estrogen receptor(ER) , GH-RH-R, GnRH-R). We have obtained two major results as follows.
1. In FSH secreting pituitary adenomas, the combination of GATA-2 and SF-1 is important as molecular mechanisms for the production of FSH. Lack of functioning Pit-1 is also essential in this group.This mechanism is comparable to that reported in the normal pituitary cells. The questions why FSH is more frequently expressed in
… More
the gonadotropin secreting adenomas and why they occur more exclusively in male remained to be further investigated.
2.. By RT-PCR, more than 40% of the non-functioning pituitary adenomas expressed mRNA for SU, FSHSU, or LHSU. Frequently these mENAs were co-expressed, especially SU and FSHSU. IHC results were comparable to these figures. Less frequently, the tumor expressed GH, PRL,TSH or ACTH. Regarding the transcription factors, all transcription factors were expressed in all tumors with very high frequency. The highest combination with Lxh3, the earliest transcription factor in the pituitary development, GATA-2, SF-1, DAX1 and GnRH-R were the most frequent factors detected. These results indicate that the significant proportion of the non-functioning pituitary adenomas are equipptd with the molecular mechanisms for the production of gonadotropins, or subunits.
The HP75 cells expressed the multiple hormones including SU, FSHSU and ACTH(POMC) and multiple transcription factors includingPtx-1, Prop-1, GATA-2, DAX1, NeuroDl and Tpit.. Our data further support the current proposal that the translineage production of hormones, which is known as a rare event in both functioning and non-functioning pituitary adenomas, is based on the "translineage expression" of transcription factors. Less
|
