Differentiation of Lactotrope Precursor GHFT Cells in Response to Fibroblast Growth Factor-2

López-Fernández, Judith; Palacios, Daniela; Castillo, Ana Isabel; Tolón, Rosa M.; Aranda, Ana; Karin, Michael

doi:10.1074/jbc.m002129200

Cited by 14 publications

(5 citation statements)

References 46 publications

(60 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Fibroblast growth factor (FGF) 4, FGF10, and specific FGF receptors have profound effects on pituitary cell differentiation and proliferation (57)(58)(59)(60)(61). PIT1-positive, hormone-negative cells can be induced to differentiate into lactotropes after exposure to FGF2 (62). A variety of signals may be important for proliferation of the PIT1 lineage and its derivatives during postnatal development.…”

Section: Discussionmentioning

confidence: 99%

Cell Proliferation and Vascularization in Mouse Models of Pituitary Hormone Deficiency

Ward

Stone

Raetzman

et al. 2006

Molecular Endocrinology

View full text Add to dashboard Cite

Mutations in the transcription factors PIT1 (pituitary transcription factor 1) and PROP1 (prophet of Pit1) lead to pituitary hormone deficiency and hypopituitarism in mice and humans. To determine the basis for this, we performed histological analysis of Pit1- and Prop1-deficient dwarf mouse pituitaries throughout fetal and postnatal development. Pit1-deficient mice first exhibit pituitary hypoplasia after birth, primarily caused by reduced cell proliferation, although there is some apoptosis. To determine whether altered development of the vascular system contributes to hypopituitarism, we examined vascularization from embryonic d 14.5 and throughout development. No obvious differences in vascularization are evident in developing Pit1-deficient pituitaries. In contrast, the Prop1-deficient mouse pituitaries are poorly vascularized and dysmorphic, with a striking elevation in apoptosis. At postnatal d 11, apoptosis-independent caspase-3 activation occurs in thyrotropes and somatotropes of normal but not mutant pituitaries. This suggests that Prop1 and/or Pit1 may be necessary for caspase-3 expression. These studies provide further insight as to the mechanisms of Prop1 and Pit1 action in mice.

show abstract

Section: Discussionmentioning

confidence: 99%

Cell Proliferation and Vascularization in Mouse Models of Pituitary Hormone Deficiency

Ward

Stone

Raetzman

et al. 2006

Molecular Endocrinology

View full text Add to dashboard Cite

show abstract

“…In a previous study, we showed that, in aggregates from 14‐day‐old rat pituitary glands, there is a considerable proportion of mitotic cells that express Pit‐1 protein but none of the Pit‐1‐dependent hormone proteins (55), which is consistent with a pathway of conversion of nonhormonal cells into lactotrophs. Also in support of such pathway is the fact that a progenitor cell line has been generated, which expresses Pit‐1 but not GH and PRL and in which FGF‐2 treatment elicits PRL gene expression (56). Thus, it is possible that T3 stimulates mitosis of nonhormonal cells that convert to PRL cells.…”

Section: Discussionmentioning

confidence: 99%

Triiodothyronine Expands the Lactotroph and Maintains the Lactosomatotroph Population, Whereas Thyrotrophin‐Releasing Hormone Augments Thyrotroph Abundance in Aggregate Cell Cultures of Postnatal Rat Pituitary Gland

Pals

Vankelecom

Denef

2006

J Neuroendocrinology

View full text Add to dashboard Cite

In the present study, we used a three-dimensional pituitary cell culture system from early postnatal rats to examine the in vitro developmental potential of triiodothyronine (T3) and thyrotrophin-releasing hormone (TRH). Cell types were identified at the hormone mRNA level by single-cell reverse transcription-polymerase chain reaction and any change in abundance was further examined by immunofluorescence staining of the corresponding hormone protein. In aggregates from 14-day-old rats, long-term (12-16 days) treatment with T3 (0.5 nM) increased the abundance of cells expressing prolactin mRNA (PRLmRNA cells) by 2.5-fold and lowered that of nonhormonal cells and thyroid-stimulating hormone beta (TSHbeta)mRNA cells. The abundance of growth hormone (GH)mRNA cells decreased during culture compared to that in the freshly dispersed pituitary gland and T3 did not significantly affect this cell population. Cells coexpressing PRL mRNA and GH mRNA virtually disappeared during culture but reappeared in the presence of T3. T3 increased the abundance of PRL-immunoreactive (ir) cells in aggregates from 14-day-old rats, as well as in aggregates from newborn and 1-week-old rats. As estimated by bromodeoxyuridine (BrdU) labelling, a 3-day treatment with T3 enhanced the number of PRL-ir cells that had incorporated BrdU, but did not yet expand the total population of PRL-ir cells. Long-term treatment with TRH (100 nM) did not affect the proportion of PRLmRNA or GHmRNA cells, but consistently increased the proportional number of TSHbeta(mRNA) and TSHbeta-ir cells. The present data confirm the findings obtained in recent in vivo loss of function genetic studies suggesting that T3 plays a prominent role in postnatal expansion of the lactotroph population and that TRH is important for thyrotroph development. The data suggest that the effect of T3 is brought about by a direct action on the pituitary gland through a cell proliferation mechanism. T3 also appears to support the lactosomatotroph population. In view of the established theory that lactotrophs develop from GH-expressing progenitor cells and that this is a post mitotic event, we propose that T3 is mitogenic for GHmRNA cells that lack GH-ir material and that transdifferentiate into PRL-ir cells, but that a pathway of PRL cell development from mitotic nonhormonal cell progenitors may also be involved.

show abstract

“…Reporter plasmids containing different fragments of the rat PRL 5Ј-flanking region have been previously described (5,29). The mutated constructs were obtained with the Pfu Turbo DNA polymerase (Stratagene), by using the oligonucleotide 5Ј-TGCTTTGGTCTCAGAAGATTCAG-3Ј (boldface indicates mutated bases).…”

Section: Methodsmentioning

confidence: 99%

A Permissive Retinoid X Receptor/Thyroid Hormone Receptor Heterodimer Allows Stimulation of Prolactin Gene Transcription by Thyroid Hormone and 9-cis-Retinoic Acid

Castillo

Martínez

Moreno

et al. 2004

Molecular and Cellular Biology

Self Cite

View full text Add to dashboard Cite

Heterodimers of the retinoid X receptor (RXR) with the thyroid hormone receptor (TR) are considered to be nonpermissive. It is believed that within these complexes RXR acts as a "silent partner." We demonstrate here that a permissive heterodimer mediates stimulation of prolactin expression by the thyroid hormone T3 and by 9-cis retinoic acid (9-cis-RA). A response element located in the prolactin distal enhancer mediates transactivation by both ligands in pituitary cells, and RXR recruits coactivators when bound to this element as a heterodimer with TR. Furthermore, transcription by the RXR agonist can be obtained in CV-1 cells only after overexpression of coactivators, and overexpression of corepressors inhibits the response in pituitary cells. Thus, cell type-specific differences in coregulator recruitment can determine the cellular response to both ligands. Coactivator recruitment by 9-cis-RA requires the ligand-dependent transactivation domains (AF-2) of both heterodimeric partners. Interestingly, the presence of the RXR ligand can overcome the deleterious effect of the AF-2 mutation E401Q on association with coactivators and transactivation. These results demonstrate an unexpected role for RXR in TR signaling and show that in particular cellular environments this receptor can act as a "nonsilent" partner of TR, allowing stimulation by RXR agonists.

show abstract

Differentiation of Lactotrope Precursor GHFT Cells in Response to Fibroblast Growth Factor-2

Cited by 14 publications

References 46 publications

Cell Proliferation and Vascularization in Mouse Models of Pituitary Hormone Deficiency

Cell Proliferation and Vascularization in Mouse Models of Pituitary Hormone Deficiency

Triiodothyronine Expands the Lactotroph and Maintains the Lactosomatotroph Population, Whereas Thyrotrophin‐Releasing Hormone Augments Thyrotroph Abundance in Aggregate Cell Cultures of Postnatal Rat Pituitary Gland

A Permissive Retinoid X Receptor/Thyroid Hormone Receptor Heterodimer Allows Stimulation of Prolactin Gene Transcription by Thyroid Hormone and 9-cis-Retinoic Acid

Contact Info

Product

Resources

About