Effect of bisphenol a on occurrence and progression of prolactinoma and its underlying mechanisms.
OBJECTIVE
To investigate the effects of Bisphenol A (BPA) on prolactin (PRL) release, pituitary cell proliferation, prolactinoma formation in estrogen-sensitive Fischer 344 (F344) rats.


METHODS
Four-week-old female F344 rats were orally administered with different concentrations of BPA or intraperitoneal injection of estradiol benzoate (estradiolbenzoate, E2) for 12 weeks. Bodyweight, blood RPL level and pituitary weights were observed and recorded. Real-time PCR, western blot and immunohistochemistry analysis were used to detect the mRNA and protein levels of the proliferation markers, including proliferating cell neclear antigen (PCNA), pituitary tumor-transforming gene (PTTG) and its relevant marker ERα. Plasma and urine BPA concentration in patients with prolactinoma and healthy participants were measured as well.


RESULTS
Body weights of the rats treated with BPA were significantly decreased compared with those in the control group. The plasma PRL level and the pituitary weights of the rats were higher than those in the control group after BPA treatment. Compared with the control group, the pituitary mRNA and protein expression levels of PCNA and PTTG were significantly increased after BPA treatment. Moreover, ERα expression level was enhanced by the treatment of BPA in comparison with that of the control group. Finally, the plasma BPA concentration in the prolactin tumor patients was significantly higher than that in the healthy participants.


CONCLUSIONS
BPA can significantly promote pituitary cell proliferation and prolactin secretion in F344 rats, which may have impact on the proliferation and secretion of pituitary cell function through the ERα pathway.
Department of Endocrinology, Qilu Hospital, Shandong UniversityJinan 250012, China; Yancheng City No. 1 People's HospitalYancheng 224001, China.
Lanxiang
L
Hao
Department of Endocrinology, Qilu Hospital, Shandong University Jinan 250012, China.
Jing
J
Zhang
Department of Endocrinology, Qilu Hospital, Shandong UniversityJinan 250012, China; Department of Endocrinology, The First Affiliated Hospital, Baotou Medical CollegeBaotou 014010, China.
Yonghong
Y
Zhang
Yancheng City No. 1 People's Hospital Yancheng 224001, China.
Haitao
H
Hu
Yancheng City No. 1 People's Hospital Yancheng 224001, China.
Weiwei
W
Shao
Heze Medical College Heze 274000, China.
Xiaochen
X
Zhang
Institute of Clinical Pharmacology, Qilu Hospital, Shandong University Jinan 250012, China.
Chunmei
C
Geng
Institute of Clinical Pharmacology, Qilu Hospital, Shandong University Jinan 250012, China.
Yanyan
Y
Wang
Department of Endocrinology, Qilu Hospital, Shandong University Jinan 250012, China.
Ling
L
Jiang
Prolactinomas; bisphenol A; cell proliferation; estradiol; prolactin secretion