Abstract
Bioactivity of many peptides depends upon post-translational α-amidation of inactive precursors by two enzyme activities known collectively as peptidylglycine α-amidating monooxygenase (PAM). PAM enzymes are particularly abundant in the pituitary. The distribution of PAM immunoreactivity and messenger ribonucleic acid (mRNA) in the adult human pituitary and in pituitary tumours was investigated by use of immunocytochemistry and in situ hybridisation. Immunoreactivity was present in numerous cells of the anterior lobe: staining was intense in a proportion of gonadotrophs and folliculo-stellate cells, but weaker in the majority of somatotrophs and lactotrophs, a few corticotrophs and occasional thyrotrophs. PAM staining was also present in nerves, pituicytes and some endocrine cells within the posterior lobe (the human intermediate zone). Forty pituitary tumours of various types were immunoreactive for PAM; more intensely and uniformly stained than normal anterior lobe. In situ hybridisation with digoxigenin-labelled probes demonstrated intense labelling for PAM mRNA in numerous cells in normal anterior pituitary and in tumours. Many regulatory peptides that require amidation for activity, potential targets for PAM, are present in the pituitary. Many tumour growth factors also require amidation and PAM may regulate these mitogenic peptides in tumours.
Similar content being viewed by others
References
Bach MA, Bondy CA (1992) Anatomy of the pituitary insulin-like growth factor system. Endocrinology 131:2588–2594
Baes M, Allaerts W, Denef C (1987) Evidence for functional communication between folliculo-stellate cells and hormone-secreting cells in perifused anterior pituitary cell aggregates. Endocrinology 120:685–691
Braas KM, Stoffers DA, Eipper BA, May V (1989) Tissue specific expression of rat peptidylglycine α-amidating monooxygenase activity and mRNA. Mol Endocrinol 3:1387–1398
Cuttitta F (1993) Peptide amidation: signature of bioactivity. Anat Rec 236:87–93
Eipper BA, Mains RE (1988) Peptide α-amidation. Annu Rev Physiol 50:333–344
Eipper BA, Stoffers DA, Mains RE (1992) The biosynthesis of neuropeptides: peptide α-amidation. Annu Rev Neurosci 15:57–85
Fenger M, Johnsen AH (1988) α-Amidated peptides derived from pro-opiomelanocortin in normal human pituitary. Biochem J 250:781–788
Gibson SJ, Polak JM (1990) Principles and applications of complementary RNA probes. In: Polak JM, McGee JO'D (eds) In situ hybridisation; principles and practice. Oxford University Press, New York 81–94
Glauder J, Ragg H, Rauch J, Engels JW (1990) Human peptidylglycine α-amidating monooxygenase: cDNA, cloning and functional expression of a truncated form in COS cells. Biochem Biophys Res Commun 169:551–558
Gon G, Giaid A, Steel JH, O'Halloran DJ, Van Noorden S, Ghatei MA, Jones PM, Amara SG, Ishikawa H, Bloom SR, Polak JM (1990) Localization of immunoreactivity for calcitonin gene-related peptide in the rat anterior pituitary during ontogeny and gonadal steroid manipulations and detection of its messenger RNA. Endocrinology 127:2618–2629
Harvey S (1990) Thyrotrophin-releasing hormone: a growth hormone-releasing factor. J Endocrinol 125:345–358
Hsu SM, Raine L, Fanger H (1981) The use of antiavidin antibody and avidin-biotin-peroxidase complex in immunoperoxidase technics. Am J Clin Pathol 75:816–821
Huang WM, Gibson SJ, Facer P, Gu J, Polak JM (1983) Improved section adhesion for immunocytochemistry using high molecular weight polymers of L-lysine as a slide coating. Histochemistry 77:275–279
Jones PM, Ghatei MA, Steel JH, O'Halloran DJ, Gon G, Legon S, Burrin JM, Leonhardt U, Polak JM, Bloom SR (1989) Evidence for neuropeptide Y synthesis in the rat anterior pituitary and the influence of thyroid hormone status: comparison with vasoactive intestinal polypeptide, substance P and neurotensin. Endocrinology 125:334–341
Jones TH, Brown BL, Dobson PRM (1990) Paracrine control of anterior pituitary secretion. J Endocrinol 127:5–13
Kato Y, Iwasaki J, Abe H, Yanaihara N, Imura H (1978) Prolactin release by vasoactive intestinal polypeptide in rats. Endocrinology 103:554–558
Martínez A, Montuenga LM, Springall DR, Treston A, Cuttitta F, Polak JM (1993) Immunocytochemical localization of peptidylglycine alpha-amidating monooxygenase enzymes (PAM) in human endocrine pancreas. J Histochem Cytochem 41:375–380
May V, Ouafik L'H, Eipper BA, Braas KM (1990) Immunocytochemical and in situ hybridization studies of peptidylglycine α-amidating monooxygenase in pituitary gland. Endocrinology 127:358–364
Murakami Y, Kato Y, Koshiyama H, Inoue T, Yanaihara N, Imura H (1987) Galanin stimulates growth hormone (GH) secretion via GH-releasing factor (GRF) in conscious rats. Eur J Pharmacol 136:415–418
Noguchi M, Takahashi K, Okamoto H (1989) Rat peptidylglycine α-amidating enzyme: the relation between activities at neutral and alkaline pH values. Arch Biochem Biophys 275:505–513
O'Halloran DJ, Jones PM, Bloom SR (1991) Neuropeptides synthesised in the anterior pituitary: possible paracrine role. Mol Cell Endocrinol 75:C7-C12
Oldham CD, Li C, Girard PR, Nerem RM, May SW (1992) Peptide amidating enzymes are present in cultured endothelial cells. Biochem Biophys Res Commun 184:323–329
Ouafik L'H, May V, Saffen DW, Eipper BA (1990) Thyroid hormone regulation of peptidylglycine α-amidating monooxygenase expression in anterior pituitary gland. Mol Endocrinol 4:1497–1505
Perkins SN, Husten EJ, Eipper BA (1990) The 108-kDa peptidylglycine alpha-amidating monooxygenase contains two separate enzymatic activities involved in peptide amidation. Biochem Biophys Res Commun 171:926–932
Polak JM, Gibson SJ, Gentleman S, Steel JH, Van Noorden S (1991) Galanin: distribution, ontogeny and expression following manipulation of the endocrine and nervous systems. In: Hökfelt T, Bartfai T, Jacobowitz D, Ottoson D (eds) Galanin, a new multifunctional peptide in the neuroendocrine system. Macmillan Press, London, pp 117–134
Quinn KA, Treston AM, Scott FM, Kasprzyk PG, Avis I, Siegfried JM, Mulshine JL, Cuttitta F (1991) α-amidation of peptide hormones in lung cancer. Cancer Cells 3:504–510
Rettori V, Pazosmoura CC, Moura EG, Polak JM, McCann SM (1992) Role of neuromedin-B in control of the release of thyrotropin in hypothyroid and hyperthyroid rats. Proc Natl Acad Sci USA 89:3035–3039
Roth KA, Krause JE (1990) Substance-P is present in a subset of thyrotrophs in the human pituitary. J Clin Endocrinol Metab 71:1089–1095
Shu S, Ju G, Fan L (1988) The glucose oxidase-DAB-nickel method in peroxidase histochemistry of the nervous system. Neurosci Lett 85:169–170
Steel JH, Van Noorden S, Ballesta J, Gibson SJ, Ghatei MA, Burrin J, Leonhardt U, Domin J, Bloom SR, Polak JM (1988) Localization of 7B2, neuromedin B, and neuromedin U in specific cell types of rat, mouse and human pituitary, in rat hypothalamus and in 30 human pituitary and extra-pituitary tumors. Endocrinology 122:270–282
Steel JH, Gon G, O'Halloran DJ, Jones PM, Yanaihara N, Ishikawa H, Bloom SR, Polak JM (1989) Galanin and vasoactive intestinal polypeptide are colocalised with classical pituitary hormones and show plasticity of expression. Histochemistry 93:183–189
Steel JH, O'Halloran DJ, Emson MA, Van Noorden S, Bloom SR, Polak JM (1992) Identification of bombesin-immunoreactive cells in rat, human and other mammalian pituitaries, their ontogeny and the effect of endocrine manipulations in the rat. Endocrinology 130:2587–2596
Thiele EA, Marek KL, Eipper BA (1989) Tissue-specific regulation of peptidyl α-amidating monooxygenase expression. Endocrinology 125:2279–2288
Treston AM, Mulshine JL, Cuttitta F (1992) Control of tumour cell biology through regulation of peptide hormone processing. Monogr Natl Cancer Inst 13:169–175
Vale W, Spiess J, Rivier J (1981) Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and β-endorphin. Science 213:1394–1397
Wand GS, Ney RL, Baylin S, Eipper B, Mains RE (1985) Characterization of a peptide alpha-amidation activity in human plasma and tissues. Metabolism 34:1044–1052
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Steel, J.H., Martínez, A., Springall, D.R. et al. Peptidylglycine α-amidating monooxygenase (PAM) immunoreactivity and messenger RNA in human pituitary and increased expression in pituitary tumours. Cell Tissue Res 276, 197–207 (1994). https://doi.org/10.1007/BF00354800
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00354800