This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cruz-Soto, M. E. Articles by Horseman, N. D. Search for Related Content PubMed PubMed Citation Articles by Cruz-Soto, M. E. Articles by Horseman, N. D.

Pituitary Tumorigenesis in Prolactin Gene-Disrupted Mice

Molecular and Cellular Physiology (M.E.C.-S., N.D.H.), Departments of Obstetrics and Gynecology (M.D.S.) and Pathology and Laboratory Medicine (G.P.B.), University of Cincinnati College of Medicine, Cincinnati, Ohio 45267; and Department of Pharmacological and Physiological Sciences, St. Louis University (K.A.G.), St. Louis, Missouri 63104

Address all correspondence and requests for reprints to: Nelson D. Horseman, Ph.D., Department of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, Ohio 45267-0576. E-mail: nelson.horseman{at}uc.edu.

Targeted disruption [knockout (KO)] of the mouse prolactin (PRL) gene created an animal model of primary isolated PRL deficiency in which there is no detectable PRL bioactivity. Pituitary glands of young adult female PRLKO mice were hyperplastic, and many cells had expanded cytoplasms with granular accumulations of an N-terminal peptide encoded by the disrupted PRL gene (KO/10 peptide). Confocal imaging showed that the pituitaries in PRL^+/+ and PRL^+/- females contained dense accumulations of apparently Golgi-associated immunoreactive PRL. PRLKO female mice (15–18 months old) developed hyperemic pituitary adenomas. The pituitary tumors in PRLKO mice synthesized the KO/10 peptide, which implies that the tumors arise from the lactotroph lineage. Anchorage-independent growth was observed among pituitary cells from PRLKO mice, aged 8 months or older, but not in cells from 3-month-old PRLKO mice. GH cells appeared to be normal in PRLKO pituitaries, but were displaced by the hyperplastic and hypertrophic growth of KO/10-positive cells. Bromocriptine suppressed mean pituitary weight in 8-month-old PRLKO mice compared with vehicle-treated PRLKO animals (20 ± 0.01 and 60 ± 10 mg; P < 0.01). We infer that pituitary lactotrophs of PRLKO mice suffer from a dual pathology that includes hypertrophy resulting from endoplasmic reticulum expansion and hyperplasia, with adenomatous transformation, in part as a consequence of disrupted dopaminergic feedback regulation.

This article has been cited by other articles:

				N. Ben-Jonathan, C. R. LaPensee, and E. W. LaPensee What Can We Learn from Rodents about Prolactin in Humans? Endocr. Rev., February 1, 2008; 29(1): 1 - 41. [Abstract] [Full Text] [PDF]

				C. R. LaPensee, N. D. Horseman, P. Tso, T. D. Brandebourg, E. R. Hugo, and N. Ben-Jonathan The Prolactin-Deficient Mouse Has an Unaltered Metabolic Phenotype Endocrinology, October 1, 2006; 147(10): 4638 - 4645. [Abstract] [Full Text] [PDF]

				V. Chesnokova, K. Kovacs, A.-V. Castro, S. Zonis, and S. Melmed Pituitary Hypoplasia in Pttg-/- Mice Is Protective for Rb+/- Pituitary Tumorigenesis Mol. Endocrinol., September 1, 2005; 19(9): 2371 - 2379. [Abstract] [Full Text] [PDF]

				H. P. Mohammad, R. A. Abbud, A. F. Parlow, J. S. Lewin, and J. H. Nilson Targeted Overexpression of Luteinizing Hormone Causes Ovary-Dependent Functional Adenomas Restricted to Cells of the Pit-1 Lineage Endocrinology, October 1, 2003; 144(10): 4626 - 4636. [Abstract] [Full Text] [PDF]