**1. Introduction**

194 Prolactin

Metab. 2000 Dec;85(12):4908-11.

2002;61:1329–39.

1):17-29. Review.

Nov;342(2):273-81.

S A. 1998 Jun 23;95(13):7795-8.

50.

6.

Takaya K, Ariyasu H, Kanamoto N, Iwakura H, Yoshimoto A, Harada M, Mori K, Komatsu Y, Usui T, Shimatsu A, Ogawa Y, Hosoda K, Akamizu T, Kojima M, Kangawa K, Nakao K. Ghrelin strongly stimulates growth hormone release in humans. J Clin Endocrinol

Tena-Sempere M, Aguilar E, Fernandez-Fernandez R, Pinilla L. Ghrelin inhibits prolactin

Tomic M, et al. Ca(2+)-mobilizing endothelin-A receptors inhibit voltage-gated Ca(2+) influx through G(i/o) signaling pathway in pituitary lactotrophs. Mol Pharmacol.

Toth BE, Bodnar I, Homicsko KG, Fülöp F, Fekete MI, Nagy GM. Physiological role of salsolinol: its hypophysiotrophic function in the regulation of pituitary prolactin

Toth BE, Homicsko K, Radnai B, Maruyama W, DeMaria JE, Vecsernyes M, Fekete MI, Fülöp F, Naoi M, Freeman ME, Nagy GM. Salsolinol is a putative endogenous neurointermediate lobe prolactin-releasing factor. J Neuroendocrinol. 2001 Dec;13(12):1042-

Van Goor F, Zivadinovic D, Martinez-Fuentes AJ, Stojilkovic SS. Dependence of pituitary hormone secretion on the pattern of spontaneous voltage-gated calcium influx. Cell type-specific action potential secretion coupling. J Biol Chem. 2001 Sep 7;276(36):33840-

Vecsernyes M, Krempels K, Toth EB, Julesz J, Makara GB, Nagy GM. Effect of posterior pituitary denervation (PPD) on prolactin (PRL) and -melanocyte-stimulating hormone

Wenger T, Toth BE, Juanéda C, Leonardelli J, Tramu G. The effects of cannabinoids on the

Wera S, Hemmings BA. Serine/threonine phosphatases. Biochem. Journal 1995 Oct 1;311 (Pt

Yamada M, Inanobe A, Kurachi Y. G protein regulation of potassium ion channels.

Yasuo S, Unfried C, Kettner M, Geisslinger G, Korf HW. Localization of an endocannabinoid system in the hypophysial pars tuberalis and pars distalis of man. Cell Tissue Res. 2010

Yu WH, Kimura M, Walczewska A, Porter JC, McCann SM. Adenosine acts by A1 receptors to stimulate release of prolactin from anterior-pituitaries in vitro. Proc Natl Acad Sci U

Zemkova H, Kucka M, Li S, Gonzalez-Iglesias AE, Tomic M, Stojilkovic SS. Characterization of purinergic P2X4 receptor channels expressed in anterior pituitary cells. Am J Physiol

(MSH) secretion of lactating rats. Brain Research Bulletin 1997;43(3):313-9.

regulation of reproduction. Life Sci. 1999;65(6-7):695-701. Review.

Pharmacol Rev 1998 Dec;50(4):723-60. Review.

Endocrinol Metab. 2010 Mar;298(3):E644-51.

secretion in prepubertal rats. Neuroendocrinology. 2004 Mar;79(3):133-41.

secretion. Neurotoxicol Teratol. 2002 Sep-Oct;24(5):655-66. Review.

Prolactin (PRL) is a polypeptide hormone secreted by the anterior pituitary responsible for the growth and differentiation of the normal mammary gland and plays a role in breast cancer. It functions systemically as an endocrine factor, but PRL may also act in an autocrine/paracrine fashion in a number of other tissues. Studies in both pre- and post-menopausal women have determined a significant increased risk for breast cancer for those with serum PRL in the highest quartile [6, 7]. PRL, acting through its receptors, has been shown to increase cell proliferation and decrease apoptosis in breast cancer cells *in vitro* [3, 8]. PRL also acts as a proangiogenic factor in mammary tissues [9]. PRL exerts its effects by binding to its receptors on the surface of normal human breast epithelial and cancer cells, initiating the Jak2/Stat5, PI3K, and mitogen-activated protein kinase (MAPK) signaling pathways [3].

The PRL receptor (PRLR) is a member of the class I cytokine/hematopoietic receptor superfamily. A single hydrophobic transmembrane region separates the extracellular ligand-binding domain from the intracellular signaling domain. Five cell-associated PRLR isoforms differ only in their C-terminal cytoplasmic domains [1, 3]. The three major isoforms (long, LF; short 1a and 1b, SF1a and SF1b, respectively) are regulated by PRL itself. LF signals for many functions including growth and differentiation, whereas SF1a and SF1b act as dominant-negatives for differentiation [1, 2]. The role of the short forms in breast cell growth remains to be determined.
