Experimental Studies On The Mechanism Of Pituitary Prolactinoma Formation

The incidence of pituitary tumor is very high and next to diabetes and thyroid diseases in the endocrine system. Patient with pituitary prolactinoma ( pituitary prolactin-producing tumor or prolactin-secreting tumor ) may present with a variety of problems ( such as abnormal lactating and menstrual flow closing ) related to space occupation or endocrine dysfunction due to high prolactinemia and the oppression of macroprolactinoma on the anterior pituitary or the hypothalamus. However, it is not very clear yet about the mechanism of prolactinoma. To study the mechanism of pituitary prolactinoma formation. Also, to investigate the distribution of melatonin ( MEL) receptor mRNA in the anterior pituitary and the effects of MEL on prolactin ( PRL ) gene expression in the anterior pituitary cells ( APC ) in vitro. As MEL is a hormone secreted by the pineal gland which inhibited the releasing of some anterior pituitary hormone and the developing of breast cancer, prostate cancer and some tumor. So the present study include that: 1. To establish a standard animal model of prolactinoma in SD rat by being treated with 10mg E₂ for 2-3 months through the drug-supplying way of s.c. silicone canaliculus. 2. The effects of estradiol ( E₂ ) and its metabolites - 2-hydroxyestrone ( 2-OHE₁ ) and 2-hydroxyestradiol ( 2-OHE₂) and several bioactive substances which play a role in the control of prolactin ( PRL) secretion on the PRL gene expression in APC in vitro. 3. The effects of E₂ and its metabolites - 2-OHE₁ and 2-OHE₂ on the proliferation of APC were studied. 4. The changes of methylation status and DNase I sensitive sites of PRL gene were determined. 5. The effects of MEL on PRL gene expression and E₂-induced prolactinoma formation, and whether MEL receptor was expressed in the anterior pituitary. Our results indicated that: 1. A standard animal model of prolactinoma was established when the SD rats were treated with 1 Omg E₂ for 2-3 months by the drug-supplying way of s.c. silicone canaliculus. The weight of prolactinoma is 3.6-12.1 times of...