Effects of resveratrol on cell growth and prolactin synthesis in GH3 cells

Chao,Wang; Xuexin,Zhang; Jun,Su; Ming,Chu; Hua,Jin; Guofu,Li; Chunlei,Tan; Wanhai,Xu

doi:10.3892/etm.2014.1544

2014-April Volume 7 Issue 4

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2014-April Volume 7 Issue 4

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Article

Effects of resveratrol on cell growth and prolactin synthesis in GH3 cells

Authors:
- Wang Chao
- Zhang Xuexin
- Su Jun
- Chu Ming
- Jin Hua
- Li Guofu
- Tan Chunlei
- Xu Wanhai
View Affiliations / Copyright

Affiliations: Department of Neurosurgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China, Department of Neurosurgery, The Third Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China, Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China, Department of Urology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China
Pages: 923-928
|
Published online on: February 13, 2014

https://doi.org/10.3892/etm.2014.1544
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Abstract

Resveratrol (RE), a phytoestrogen, has antiestrogenic properties. Estrogen plays a key role in the development and progression of pituitary prolactinoma. Moreover, RE is a potent cancer chemopreventive agent that inhibits the initiation, promotion and progression of carcinogenesis. The present study investigated the antitumor effects of RE on GH3 pituitary tumor cells. A concentration‑ and treatment duration‑dependent biphasic effect of RE on the proliferation of the GH3 cells was demonstrated. After three days of treatment, RE stimulated proliferation at low concentrations and inhibited proliferation at high concentrations. However, when the treatment duration was reduced to 6 h, RE inhibited proliferation in a concentration-dependent manner. In addition, RE induced apoptosis with the activation of caspase‑3 and ‑8, and decreased the percentage of prolactin (PRL)‑immunopositive GH3 cells. Furthermore, RE suppressed expression of the PRL gene and inhibited the cell proliferation and PRL synthesis induced by 17β‑estradiol (E2). In GH3 cells, the proliferation response exhibited higher sensitivity to E2 compared with the PRL response; by contrast, the PRL response was more sensitive to RE than the proliferation response was. These results indicate that RE, an antiestrogenic compound, exerts its antitumor effect on GH3 cells through the suppression of GH3 cell growth and through the inhibition of PRL synthesis. The RE-induced cell apoptosis was shown to be caspase-dependent. Therefore, the present study provides support for the use of RE in the chemoprevention and chemotherapy of pituitary prolactinoma.

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1	Heaney AP, Fernando M and Melmed S: Functional role of estrogen in pituitary tumor pathogenesis. J Clin Invest. 109:277–283. 2002. View Article : Google Scholar : PubMed/NCBI
2	Freeman ME, Kanyicska B, Lerant A and Nagy G: Prolactin: structure, function, and regulation of secretion. Physiol Rev. 80:1523–1631. 2000.PubMed/NCBI
3	Yin P, Kawashima K and Arita J: Direct actions of estradiol on the anterior pituitary gland are required for hypothalamus-dependent lactotrope proliferation and secretory surges of luteinizing hormone but not of prolactin in female rats. Neuroendocrinology. 75:392–401. 2002. View Article : Google Scholar
4	Caporali S, Imai M, Altucci L, et al: Distinct signaling pathways mediate stimulation of cell cycle progression and prevention of apoptotic cell death by estrogen in rat pituitary tumor PR1 cells. Mol Biol Cell. 14:5051–5059. 2003. View Article : Google Scholar : PubMed/NCBI
5	Friend KE, Ang LW and Shupnik MA: Estrogen regulates the expression of several different estrogen receptor mRNA isoforms in rat pituitary. Proc Natl Acad Sci USA. 92:4367–4371. 1995. View Article : Google Scholar : PubMed/NCBI
6	Jaffrain-Rea ML, Petrangeli E, Ortolani F, et al: Cellular receptors for sex steroids in human pituitary adenomas. J Endocrinol. 151:175–184. 1996. View Article : Google Scholar : PubMed/NCBI
7	Nakao H, Koga M, Arao M, et al: Enzyme-immunoassay for estrogen receptors in human pituitary adenomas. Acta Endocrinol (Copenh). 120:233–238. 1989.PubMed/NCBI
8	Lee SY, Ahn BT, Baik SH and Lee BL: Tamoxifen inhibits GH3 cell growth in culture via enhancement of apoptosis. Neurosurgery. 43:116–123. 1998.PubMed/NCBI
9	Bowers JL, Tyulmenkov VV, Jernigan SC and Klinge CM: Resveratrol acts as a mixed agonist/antagonist for estrogen receptors alpha and beta. Endocrinology. 141:3657–3667. 2000.PubMed/NCBI
10	Jang M, Cai L, Udeani GO, et al: Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science. 275:218–220. 1997. View Article : Google Scholar : PubMed/NCBI
11	Boockfor FR, Hoeffler JP and Frawley LS: Cultures of GH3 cells are functionally heterogeneous: thyrotropin-releasing hormone, estradiol and cortisol cause reciprocal shifts in the proportions of growth hormone and prolactin secretors. Endocrinology. 117:418–420. 1985. View Article : Google Scholar
12	Iwasaka T, Umemura S, Kakimoto K, Koizumi H and Osamura YR: Expression of prolactin mRNA in rat mammary gland during pregnancy and lactation. J Histochem Cytochem. 48:389–396. 2000. View Article : Google Scholar : PubMed/NCBI
13	Shaw-Bruha CM, Pennington KL and Shull JD: Identification in the rat prolactin gene of sequences homologous to the distal promoter of the human prolactin gene. Biochim Biophys Acta. 1442:304–313. 1998. View Article : Google Scholar : PubMed/NCBI
14	Wang C, Hu ZQ, Chu M, et al: Resveratrol inhibited GH3 cell growth and decreased prolactin level via estrogen receptors. Clin Neurol Neurosurg. 114:241–248. 2012. View Article : Google Scholar : PubMed/NCBI
15	Joe AK, Liu H, Suzui M, Vural ME, Xiao D and Weinstein IB: Resveratrol induces growth inhibition, S-phase arrest, apoptosis, and changes in biomarker expression in several human cancer cell lines. Clin Cancer Res. 8:893–903. 2002.PubMed/NCBI
16	Chu M, Hu ZQ, Wei LL, Zhang SZ, Hu EX and Dong Q: Inhibitory effect of resveratrol in pituitary GH3 cells. Chin J Neurosurg. 21:105–109. 2005.(In Chinese).
17	Yamashita H, Okadome T, Franzén P, ten Dijke P, Heldin CH and Miyazono K: A rat pituitary tumor cell line (GH3) expresses type I and type II receptors and other cell surface binding protein(s) for transforming growth factor-beta. J Biol Chem. 270:770–774. 1995. View Article : Google Scholar : PubMed/NCBI
18	Kakeya T, Takeuchi S and Takahashi S: Epidermal growth factor, insulin, and estrogen stimulate development of prolactin-secreting cells in cultures of GH3 cells. Cell Tissue Res. 299:237–243. 2000. View Article : Google Scholar : PubMed/NCBI
19	Kansra S, Yamagata S, Sneade L, Foster L and Ben-Jonathan N: Differential effects of estrogen receptor antagonists on pituitary lactotroph proliferation and prolactin release. Mol Cell Endocrinol. 239:27–36. 2005. View Article : Google Scholar : PubMed/NCBI
20	Schreihofer DA, Stoler MH and Shupnik MA: Differential expression and regulation of estrogen receptors (ERs) in rat pituitary and cell lines: estrogen decreases ERalpha protein and estrogen responsiveness. Endocrinology. 141:2174–2184. 2000.
21	Mitchner NA, Garlick C, Steinmetz RW and Ben-Jonathan N: Differential regulation and action of estrogen receptors alpha and beta in GH3 cells. Endocrinology. 140:2651–2658. 1999.PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Effects of resveratrol on cell growth and prolactin synthesis in GH3 cells

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