Genetic Bases of Estrogen-Induced Pituitary Growth in an Intercross between the ACI and Copenhagen Rat Strains: Dominant Mendelian Inheritance of the ACI Phenotype*

Endocrinology ◽  
1999 ◽  
Vol 140 (6) ◽  
pp. 2828-2835 ◽  
Author(s):  
Thomas J. Spady ◽  
Karen L. Pennington ◽  
Rodney D. McComb ◽  
James D. Shull
Keyword(s):  
Cell Proliferation ◽  
Pituitary Gland ◽  
Anterior Pituitary ◽  
Molecular Mechanisms ◽  
Pituitary Tumors ◽  
Backcross Progeny ◽  
Anterior Pituitary Gland ◽  
Rat Strains ◽  
Genetic Trait ◽  
Inbred Rat

Abstract Estrogens stimulate cell proliferation in a variety of tissues and are widely believed to be contributing factors in the etiology of certain cancer types in humans. The molecular mechanisms through which estrogens regulate cell proliferation are currently unknown. Estrogens stimulate proliferation of the PRL-producing lactotroph of the rat anterior pituitary gland and induce development of PRL-producing pituitary tumors in several inbred rat strains. Therefore, the lactotroph provides a well defined model for identifying the mechanisms through which estrogens regulate cell proliferation and/or survival. Data from our laboratory and others indicate that the relative sensitivity to the pituitary growth-promoting actions of estrogens is highly strain specific. This allows genetics-based approaches to be used to address the molecular mechanisms through which estrogens stimulate lactotroph proliferation and induce pituitary tumor development. In the present study we have examined the ability of diethylstilbestrol (DES) to induce pituitary growth in the genetically related AxC-Irish (ACI) and Copenhagen (COP) strains and their derived F1, F2, and backcross progeny. The data presented herein indicate that the anterior pituitary gland of the ACI strain displays approximately a 2-fold greater growth response to administered DES than does the pituitary gland of the COP strain. The average pituitary weight in male ACI rats was increased from 9.2± 0.2 mg (mean ± sd) in untreated rats to 63.7± 12.6 mg in rats treated with DES for 12 weeks, whereas in male COP rats, DES increased pituitary weight from 12.7 ± 0.9 to 38.1± 8.2 mg. The ACI phenotype was inherited in the F1, F2, and backcross progeny of an ACI × COP intercross as a dominant genetic trait, and the approximately 30 mg of additional pituitary growth displayed by the DES-treated ACI rat, relative to that of the treated COP rat, appeared to result from the actions of a single locus. Moreover, in F1 progeny from an ACI × Brown Norway intercross, the ACI phenotype was inherited as a dominant or incompletely dominant genetic trait. These data, when compared with findings of previous studies using the Fischer 344 rat strain, provide the first indication that distinct genetic pathways contribute to regulation of estrogen-induced pituitary growth and induction of PRL-producing pituitary tumors in the ACI and F344 rat strains.

Prolactin release, oestrogens and proliferation of prolactin-secreting cells in the anterior pituitary gland of adult male rats

1986 ◽  
Vol 108 (3) ◽  
pp. 399-403 ◽  
Author(s):  
R. L. Pérez ◽  
G. A. Machiavelli ◽  
M. I. Romano ◽  
J. A. Burdman
Keyword(s):  
Cell Proliferation ◽  
Pituitary Gland ◽  
Adult Male ◽  
Anterior Pituitary ◽  
Pituitary Hormones ◽  
Anterior Pituitary Gland ◽  
Male Rats ◽  
Serum Prolactin ◽  
Prolactin Release ◽  
Experimental Conditions

ABSTRACT Relationships among the release of prolactin, the effect of oestrogens and the proliferation of prolactin-secreting cells were studied under several experimental conditions. Administration of sulpiride or oestradiol released prolactin and stimulated cell proliferation in the anterior pituitary gland of adult male rats. Clomiphene completely abolished the rise in cell proliferation, but did not interfere with the sulpiride-induced release of prolactin. Treatment with oestradiol plus sulpiride significantly increased serum prolactin concentrations and the mitotic index compared with the sum of the stimulation produced by both drugs separately. Bromocriptine abolished the stimulatory effect of oestradiol on the serum prolactin concentration and on cell proliferation. In oestradiol- and/or sulpiride-treated rats, 80% of the cells in mitoses were lactotrophs. The remaining 20% did not stain with antisera against any of the pituitary hormones. The number of prolactin-secreting cells in the anterior pituitary gland significantly increased after the administration of oestradiol or sulpiride. The results demonstrate that treatment with sulpiride and/or oestradiol increases the proliferation and the number of lactotrophs in the anterior pituitary gland of the rat. J. Endocr. (1986) 108, 399–403

scholarly journals Angiogenesis in Pituitary Adenomas and the Normal Pituitary Gland

2000 ◽  
Vol 85 (3) ◽  
pp. 1159-1162 ◽  
Author(s):  
Helen E. Turner ◽  
Zsusha Nagy ◽  
Kevin C. Gatter ◽  
Margaret M. Esiri ◽  
Adrian L. Harris ◽  
...  
Keyword(s):  
Pituitary Gland ◽  
Pituitary Adenomas ◽  
Anterior Pituitary ◽  
Pituitary Tumors ◽  
Anterior Pituitary Gland ◽  
Ulex Europaeus ◽  
Normal Pituitary Gland ◽  
Ulex Europaeus Agglutinin I ◽  
Acth Secreting ◽  
Tumor Types

Abstract Angiogenesis is essential for tumor growth beyond a few millimeters in diameter, and the intratumoral microvessel count that represents a measure of angiogenesis has been correlated with tumor behavior in a variety of different tumor types. To date no systematic study has assessed pituitary tumors of different secretory types, correlating vascular count with tumor size. The vascular densities of pituitary tumors and normal anterior pituitary were therefore assessed by counting vessels labeled using the vascular markers CD31 and ulex europaeus agglutinin I. One hundred and twelve surgically removed pituitary adenomas (30 GH-secreting, 25 prolactinomas, 15 ACTH-secreting, and 42 nonfunctioning tumors) were compared with 13 specimens of normal anterior pituitary gland. The vascular counts in the normal anterior pituitary gland were significantly higher (P < 0.05) than those in the tumors using both CD31 and ulex europaeus agglutinin I. In addition, microprolactinomas were significantly less vascular (P < 0.05) than macroprolactinomas, although there was no such difference between vascular densities of microadenomas and macroadenomas producing GH. ACTH-secreting tumors were, like microprolactinomas, of much lower vascular density than the normal pituitary and other secreting and nonsecreting tumor types. In marked contrast to other tumors, pituitary adenomas are less vascular than the normal pituitary gland, suggesting that there may be inhibitors of angiogenesis that play an important role in the behavior of these tumors.

scholarly journals Glial-Derived Neurotropic Factor and RET Gene Expression in Normal Human Anterior Pituitary Cell Types and in Pituitary Tumors

2002 ◽  
Vol 87 (4) ◽  
pp. 1879-1884 ◽  
Author(s):  
Miguel A. Japón ◽  
Angel G. Urbano ◽  
Carmen Sáez ◽  
Dolores I. Segura ◽  
Alfonso Leal Cerro ◽  
...  
Keyword(s):  
Pituitary Gland ◽  
Anterior Pituitary ◽  
Pituitary Tumors ◽  
Cell Types ◽  
Anterior Pituitary Gland ◽  
Tyrosine Kinase Receptor ◽  
Positive Immunostaining ◽  
Normal Human ◽  
Human Anterior Pituitary ◽  
Neurotropic Factor

Abstract Glial-derived neurotropic factor (GDNF) signaling is mediated through a 2-component system consisting of the so-called GDNF receptor-α (GFRα1), which binds to GDNF. This complex activates the tyrosine kinase receptor RET. In this paper we demonstrate GDNF, GFRα1, and RET mRNA and protein expression in the human anterior pituitary gland. Double immunohistochemistry of anterior pituitary sections showed GDNF immunoreactivity in more than 95% of somatotrophs and to a lesser extent in corticotrophs (20%); it was almost absent in the remaining cell types. Also, although more than 95% of somatotrophs were stained for RET, no positive immunostaining could be detected in other cell types. Furthermore, we have looked for GDNF and RET in human pituitary adenomas of various hormonal phenotypes. Strong positive immunostaining was found for c-RET in all of the GH-secreting adenomas screened as well as in 50% of ACTH-producing adenomas. Positive immunostaining for GDNF was found in all of the GH-secreting adenomas and in 10% of the corticotropinomas. Lastly, we found strong positive immunostaining for GFRα1 in 90% of the somatotropinomas and 50% of the corticotropinomas as well as in 1 of 8 prolactinomas and 1 of 13 nonfunctioning adenomas. All of the remaining pituitary tumors screened were negative for RET, GDNF, and GFRα1. This study indicates that GDNF may well be acting in the regulation of somatotroph cell growth and/or cell function in the normal human anterior pituitary gland. The expression of RET in all of the somatotropinomas and in 50% of the ACTH-producing tumors implies that GDNF and RET could be involved in the pathogenesis of pituitary tumors.

scholarly journals Somatostatin system: molecular mechanisms regulating anterior pituitary hormones

2014 ◽  
Vol 53 (1) ◽  
pp. R1-R19 ◽  
Author(s):  
Tamar Eigler ◽  
Anat Ben-Shlomo
Keyword(s):  
Pituitary Gland ◽  
Anterior Pituitary ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Hormone Secretion ◽  
Pituitary Hormones ◽  
Anterior Pituitary Gland ◽  
Gland Function ◽  
Channel Dependent

The somatostatin (SRIF) system, which includes the SRIF ligand and receptors, regulates anterior pituitary gland function, mainly inhibiting hormone secretion and to some extent pituitary tumor cell growth. SRIF-14 via its cognate G-protein-coupled receptors (subtypes 1–5) activates multiple cellular signaling pathways including adenylate cyclase/cAMP, MAPK, ion channel-dependent pathways, and others. In addition, recent data have suggested SRIF-independent constitutive SRIF receptor activity responsible for GH and ACTH inhibition in vitro. This review summarizes current knowledge on ligand-dependent and independent SRIF receptor molecular and functional effects on hormone-secreting cells in the anterior pituitary gland.

scholarly journals Cellular and Molecular Specificity of Pituitary Gland Physiology

2012 ◽  
Vol 92 (1) ◽  
pp. 1-38 ◽  
Author(s):  
Carolina Perez-Castro ◽  
Ulrich Renner ◽  
Mariana R. Haedo ◽  
Gunter K. Stalla ◽  
Eduardo Arzt
Keyword(s):  
Pituitary Gland ◽  
Anterior Pituitary ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Hormone Secretion ◽  
Regulatory System ◽  
Anterior Pituitary Gland ◽  
Complex Signals ◽  
Transcriptional Regulatory Networks ◽  
Transcriptional Regulatory

The anterior pituitary gland has the ability to respond to complex signals derived from central and peripheral systems. Perception of these signals and their integration are mediated by cell interactions and cross-talk of multiple signaling transduction pathways and transcriptional regulatory networks that cooperate for hormone secretion, cell plasticity, and ultimately specific pituitary responses that are essential for an appropriate physiological response. We discuss the physiopathological and molecular mechanisms related to this integrative regulatory system of the anterior pituitary gland and how it contributes to modulate the gland functions and impacts on body homeostasis.

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