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**Chapter 5** 

© 2013 Zhao, licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

© 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution,

distribution, and reproduction in any medium, provided the original work is properly cited.

and reproduction in any medium, provided the original work is properly cited.

**Neuregulin-1 (Nrg1):** 

Weijiang Zhao

**1. Introduction** 

http://dx.doi.org/10.5772/54716

regulator (Vlotides et al., 2009).

Nrg1α/β **(See Fig 1)**.

**An Emerging Regulator** 

**of Prolactin (PRL) Secretion** 

Additional information is available at the end of the chapter

**1.1. Definition and structure of Neuregulin-1 (Nrg1)** 

Hypothalamus-derived dopamine and thyrotrophin-releasing hormone (TRH) have long been considered the main sources of prolactin (PRL) regulators in the anterior pituitary, whereas other substances also modulate PRL expression and secretion (Borrelli et al., 1992; Cai et al., 1999; Spuch et al., 2006). Recently, Vlotides for the first time observed that recombinant Nrg1 can control PRL secretion from rat RPL and growth hormone (GH) secreting lactosomatotroph GH3 cells, suggesting the emerging role of Nrg1 as a PRL

Neuregulins are homologous to epidermal growth factor (EGF) and are mainly encoded by four alternatively spliced genes: NRG-1 to -4 (Orr-Urtreger et al., 1993). Diverse splicing of the NRG-1 gene gives rise to at least six main types of Nrg1 (types I–VI) with ectodomain variation, whereas type I to III Nrg1. are the most intensively investigated. All types of Nrg1 contain an EGF-like domain, which can be classified as either α or β (Jacobsen et al., 1996; Rosnack et al., 1994). Distinct from soluble Nrg1, a membrane-tethered Nrg1 precursor has been identified that contains a transmembrane (TM) domain and an intracellular domain (ICD). The ICD can be further characterized as ICD a, b and c. The structure that links the ectodomain and the transmembrane (TM) domain is called a stalk (S), which can be further classified as S1, S2 and S4. Proteolysis of the Nrg1 precursor, a tightly regulated process, releases the soluble domains and leads to formation of autocrineparacrine loops. However, recruitment of S3, which contains the stop codon, terminates the extension of the ectodomain into the cytoplasm and thus leads to the formation of non-membrane anchored

