Prolactin Proteoform Pattern Changed in Human Pituitary Adenoma Relative to Control Pituitary Tissues

Xianquan Zhan,Shehua Qian

doi:10.5772/intechopen.92836

Abstract

PRL gene-encoded prolactin is synthesized in the ribosome in the pituitary and then secretes into blood circulation to reach its target organ and exerts its biological roles, for example, involving in production, growth, development, immunoregulation, and metabolism. Multiple post-translational modifications and other unknown factors might be involved in this process to cause different prolactin proteoforms with differential isoelectric point (pI) and relative mass (Mr ). Pituitary adenomas are the common disease occurring in pituitary organ to affect the endocrine system. Two-dimensional gel electrophoresis (2DGE) was used to separate prolactin proteoforms according to their pI and Mr , followed by identification with Western blot and mass spectrometry (MS) analyses. Six prolactin proteoforms were identified in control pituitary tissues, and this prolactin proteoform pattern was significantly changed in different hormone subtypes of nonfunctional pituitary adenomas (NF−, LH+, FSH+, and LH+/FSH+) and prolactinomas (PRL+). Further, bioinformatics analysis revealed that different prolactin proteoforms might bind to different short- or long-PRL receptor-mediated signaling pathways. These findings clearly demonstrated that prolactin proteoform pattern existed in human pituitary and changed in different subtypes of pituitary adenomas. It is the scientific data to in-depth study prolactin functions, and to discover the prolactin proteoform biomarkers for PRL-related adenomas.

Highlights

Prolactin (PRL) is a multifunctional hormone which is synthesized and secreted by pituitary [1]
The PRL prohormone is synthesized in the ribosome, with 227 amino acids, containing a signal peptide (Table 1), which was assigned with Swiss-Prot accession No P01236
Six PRL proteoforms were identified in human pituitary tissue with 2DGE and mass spectrometry (MS) analyses, and four of six PRL proteoforms were validated with 2DGE-based Western blot, MS, and MS/MS analyses

Summary

Introduction

Prolactin (PRL) is a multifunctional hormone which is synthesized and secreted by pituitary [1]. According to the concept of proteoforms, a protein is defined as a set of proteoforms, due to different splicing, post-translational modifications (PTMs), and even unknown factors. Qian et al found six PRLs with different pI and Mr in human pituitary tissues by two-dimensional gel electrophoresis (2DGE) and mass spectrometry (MS) [9]. Zhan et al found 24 growth hormone (GH) with different pI and Mr in human pituitary tissues by 2-DGE and MS [10]. A possible reason of this difference of pI and Mr in human PRL and GH is that they undergo PTMs or splicing [11]. A proteoform is a specific form that protein exerts its final functions, which is derived from a gene undergoing splicing, transcription, translation, PTMs, translocation/re-distribution, and interaction with other molecules, etc. A proteoform is a specific form that protein exerts its final functions, which is derived from a gene undergoing splicing, transcription, translation, PTMs, translocation/re-distribution, and interaction with other molecules, etc. [12]

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Results

Conclusion