Journal of Clinical Endocrinology & Metabolism, Vol 76, 1308-1313, Copyright © 1993 by Endocrine Society

ARTICLES

Production of prolactin by smooth muscle cells cultured from human uterine fibroid tumors

RA Nowak, MS Rein, LJ Heffner, AJ Friedman and AH Tashjian Jr
Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, Massachusetts.

Uterine leiomyomas, which are myometrial smooth muscle tumors, secrete PRL. We investigated the actions of several hormones known to stimulate PRL secretion by the pituitary gland or decidua on PRL secretion by leiomyoma-derived smooth muscle cells (SMC) in monolayer culture. Cultures were verified to be SMC by immunostaining for smooth muscle alpha-action and desmin. Hormone treatments were performed in serum- free medium for 72 h. Medium was harvested every 24 h and assayed for PRL. 17 beta-Estradiol, progesterone, TRH, insulin-like growth factor- I, epidermal growth factor, and the GnRH agonist leuprolide did not affect PRL secretion by these SMC. Insulin caused a significant suppression of PRL secretion by 72 h, and this was accompanied by a 64% increase in total cell protein per well, which represented an increase in cell number. Cells were also plated at various densities to determine the effects of cell number on PRL secretion. The amount of PRL secreted per 1000 cells decreased significantly as cell number per well increased. Northern blot analysis identified PRL mRNA in fresh leiomyoma tissue. PRL mRNA in three independent cultures of SMC was then detected by reverse transcription and the polymerase chain reaction. Hybridization occurred only with the expected band of approximately 423 basepairs in size. We conclude that leiomyomas express PRL mRNA in vivo and that leiomyoma-derived SMC in culture continue to express the PRL mRNA and secrete PRL in the absence of ovarian steroids. PRL secretion by SMC in culture appears to be modulated primarily by changes in cell density.

This article has been cited by other articles:

				H. R. Mason, A. C. Lake, J. E. Wubben, R. A. Nowak, and J. J. Castellot Jr The growth arrest-specific gene CCN5 is deficient in human leiomyomas and inhibits the proliferation and motility of cultured human uterine smooth muscle cells Mol. Hum. Reprod., March 1, 2004; 10(3): 181 - 187. [Abstract] [Full Text] [PDF]

				H. R. Mason, R. A. Nowak, C. C. Morton, and J. J. Castellot Jr. Heparin Inhibits the Motility and Proliferation of Human Myometrial and Leiomyoma Smooth Muscle Cells Am. J. Pathol., June 1, 2003; 162(6): 1895 - 1904. [Abstract] [Full Text] [PDF]

				H. Shime, M. Kariya, A. Orii, C. Momma, T. Kanamori, K. Fukuhara, T. Kusakari, Y. Tsuruta, K. Takakura, T. Nikaido, et al. Tranilast Inhibits the Proliferation of Uterine Leiomyoma Cells in Vitro through G1 Arrest Associated with the Induction of p21waf1 and p53 J. Clin. Endocrinol. Metab., December 1, 2002; 87(12): 5610 - 5617. [Abstract] [Full Text] [PDF]

				E. A. Stewart Gonadotropins and the Uterus: Is There a Gonad-Independent Pathway? Reproductive Sciences, December 1, 2001; 8(6): 319 - 326. [Abstract] [PDF]

				B.-S. Lee and R. A. Nowak Human Leiomyoma Smooth Muscle Cells Show Increased Expression of Transforming Growth Factor-{beta}3 (TGF{beta}3) and Altered Responses to the Antiproliferative Effects of TGF{beta} J. Clin. Endocrinol. Metab., February 1, 2001; 86(2): 913 - 920. [Abstract] [Full Text]

				A. G. Herzog Migraine with ectopic hyperprolactinemia from uterine fibroids Neurology, July 12, 2000; 55(1): 148 - 149. [Full Text] [PDF]

				A. Horiuchi, T. Nikaido, T. Yoshizawa, K. Itoh, Y. Kobayashi, T. Toki, I. Konishi, and S. Fujii HCG promotes proliferation of uterine leiomyomal cells more strongly than that of myometrial smooth muscle cells in vitro Mol. Hum. Reprod., June 1, 2000; 6(6): 523 - 528. [Abstract] [Full Text] [PDF]

				A. Horiuchi, T. Nikaido, Z. Ya-Li, K. Ito, A. Orii, and S. Fujii Heparin inhibits proliferation of myometrial and leiomyomal smooth muscle cells through the induction of {alpha}-smooth muscle actin, calponin h1 and p27 Mol. Hum. Reprod., February 1, 1999; 5(2): 139 - 145. [Abstract] [Full Text] [PDF]

				S. S. Palmer, D. Haynes-Johnson, T. Diehl, and R. A. Nowak Increased Expression of Stromelysin 3 mRNA in Leiomyomas (Uterine Fibroids) Compared With Myometrium Reproductive Sciences, July 1, 1998; 5(4): 203 - 209. [Abstract] [PDF]

				C. Bole-Feysot, V. Goffin, M. Edery, N. Binart, and P. A. Kelly Prolactin (PRL) and Its Receptor: Actions, Signal Transduction Pathways and Phenotypes Observed in PRL Receptor Knockout Mice Endocr. Rev., June 1, 1998; 19(3): 225 - 268. [Abstract] [Full Text]

				B.-S. Lee, S. B. Margolin, and R. A. Nowak Pirfenidone: A Novel Pharmacological Agent That Inhibits Leiomyoma Cell Proliferation and Collagen Production J. Clin. Endocrinol. Metab., January 1, 1998; 83(1): 219 - 223. [Abstract] [Full Text]