Abstract
Human prolactin (hPRL) plays multiple roles in growth, metabolism, development, reproduction, and immunoregulation, which is an important protein synthesized in a pituitary. Two-dimensional gel electrophoresis (2DE) is an effective method in identity of protein variants for in-depth insight into functions of that protein. 2DE, 2DE-based PRL-immunoblot, mass spectrometry, and bioinformatics were used to analyze hPRL variants in human normal (control; n = 8) pituitaries and in five subtypes of pituitary adenomas [NF− (n = 3)-, FSH+ (n = 3)-, LH+ (n = 3)-, FSH+/LH+ (n = 3)-, and PRL+ (n = 3)-adenomas]. Six hPRL variants were identified with different isoelectric point (pI)-relative molecular mass (Mr) distribution on a 2DE pattern, including variants V1 (pI 6.1; 26.0 kDa), V2 (pI 6.3; 26.4 kDa), V3 (pI 6.3; 27.9 kDa), V4 (pI 6.5; 26.1 kDa), V5 (pI 6.8; 25.9 kDa), and V6 (pI 6.7; 25.9 kDa). Compared to controls, except for variants V2-V6 in PRL-adenomas, V2 in FSH+-adenomas, and V3 in NF−-adenomas, the other PRL variants were significantly downregulated in each subtype of pituitary adenomas. Moreover, the pattern of those six PRL variants was significantly different among five subtypes of pituitary adenomas relative to control pituitaries. Different hPRL variants might be involved in different types of PRL receptor-signaling pathways in a given condition. Those findings clearly revealed the existence of six hPRL variants in human pituitaries, and the pattern changes of six hPRL variants among different subtypes of pituitary adenomas, which provide novel clues to further study the functions, and mechanisms of action, of hPRL in human pituitary and in PRL-related diseases, and the potential clinical value in pituitary adenomas.
Highlights
Prolactin (PRL) is a four long α-helix protein hormone, which was discovered in mammals in the 1930s by Oscar Riddle, and in humans in the 1970s by Friesen et al [1]
Human control pituitary glands were post-mortem tissues obtained from the National Disease Research Interchange (n = 1) and the Memphis Regional Medical Center (n = 7), which were approved by University of Tennessee Health Science Center (UTHSC) Internal Review Board (IRB)
Human pituitary adenoma tissues were obtained from the Emory University Hospital, which were approved by Emory University Hospital IRB, and Department of Neurosurgery of Xiangya Hospital, which were approved by the Xiangya Hospital Medical Ethics Committee of Central South University, China
Summary
Prolactin (PRL) is a four long α-helix protein hormone, which was discovered in mammals in the 1930s by Oscar Riddle, and in humans in the 1970s by Friesen et al [1]. The hPRL cDNA consists of 914 nucleotides and includes a 681-nucleotide open-reading frame that encodes the PRL prohormone with 227 amino acids (positions 1–227), 25.9 kDa, which contains a signal peptide in amino acid positions 1-28 (Table 1). PRL is a polypeptide hormone with complex function, and is synthesized and secreted in the anterior pituitary gland, and in other tissues and organs, such as skin, prostate, and the immune system. Hypothalamic regulation of pituitary PRL secretion is largely inhibitory. PRL transports to the target tissues mammary gland, prostate, liver, and ovary via the blood circulation to bind to two different types of short or long PRL receptors (PRLRs) to activate signal pathways, which include JaK2 activation, Ras-RafMAPK pathway, modulatory pathways, PI3K and downstream pathways, and stats [4]. PRLs that interact with different short or long PRLRs must be different PRL variants
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