Impaired Development of Somatotropes, Lactotropes and Thyrotropes in Growth-Retarded (grt) Mice

Kobayashi, Kenichi; Yamamoto, Kazutoshi; Kikuyama, Sakaé; Machida, Takeo; Kobayashi, Tetsuya

doi:10.1293/tox.22.187

Cited by 4 publications

(5 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…S1A; Supplementary Data are available online at www.liebertpub.com/scd). Moreover, proportions were comparable to data reported in other studies [18][19][20].…”

Section: Treatment With Dtsupporting

confidence: 89%

Regenerative Capacity of the Adult Pituitary: Multiple Mechanisms of Lactotrope Restoration After Transgenic Ablation

Vankelecom²

2012

Stem Cells and Development

View full text Add to dashboard Cite

In a recent study, we showed that the adult pituitary gland is capable of regenerating transgenically ablated growth hormone-producing (GH(+)) somatotropes. Here, we investigated whether the gland's regenerative capacity is more general and also applies to the other major hormonal cell type, the prolactin-producing (PRL(+)) lactotropes. We set up the transgenic PRLCre/inducible diphtheria toxin receptor (iDTR) mouse model, in which the PRL promoter drives expression of Cre that induces DTR in lactotropes. Injection of female mice with DT for different periods causes a gradual ablation of PRL(+) cells, reaching a maximum of 70% after 10-day DT treatment. During the following weeks, lactotropes progressively reappear achieving a 60% restoration after 6 weeks. The Sox2(+) stem/progenitor cell compartment displays a prompt reaction to the DT-triggered cell ablation injury, including expansion of the marginal-zone niche and coexpression of PRL, the latter only very rarely observed in control pituitary. Throughout the regeneration period (2-6 weeks), Sox2(+) as well as double Sox2(+)/PRL(+) cells continue to be more abundant than in control pituitary. In addition to this stem cell reaction, surviving or newborn lactotropes increase their proliferative activity, and bihormonal PRL(+)/GH(+) cells become detectable suggesting somatotrope-to-lactotrope transdifferentiation. In conclusion, the adult pituitary gland is capable of restoring lactotrope cells after destruction, further confirming its regenerative competence. Repair of lactotropes appears to be driven by a combination of mechanisms, including recruitment from stem cells, proliferation of lactotropes, and transdifferentiation of somatotropes.

show abstract

“…S1A; Supplementary Data are available online at www.liebertpub.com/scd). Moreover, proportions were comparable to data reported in other studies [18][19][20].…”

Section: Treatment With Dtsupporting

confidence: 89%

Regenerative Capacity of the Adult Pituitary: Multiple Mechanisms of Lactotrope Restoration After Transgenic Ablation

Vankelecom²

2012

Stem Cells and Development

View full text Add to dashboard Cite

show abstract

“…However, it has been reported that there may be no significant difference in the plasma GH levels between normal and grt mice in the peripubertal stage. (Kobayashi et al 2009). Thus, we examined on the involvement of insulin in growth retardation observed in grt mice.…”

Section: Discussionmentioning

confidence: 99%

“…However, it has been reported that there may be no significant difference in the plasma GH levels between normal and grt mice in the peripubertal stage. (Kobayashi et al . 2009).…”

Section: Discussionmentioning

confidence: 99%

“…Growth-retarded (grt) mice were first reported as arising from a spontaneous mutation in phenotypically normal Snell's dwarf (DW/J strain) mouse siblings and characteristically exhibited a growth pause followed by delayed onset of pubertal growth (Yoshida et al 1994). In addition to this severe postnatal growth retardation, impaired development of growth hormone (GH)-, prolactin (PRL)-and thyroid-stimulating hormone (TSH)-producing cells in the pituitary, and altered hormone concentrations of these hormones in the plasma are also observed in grt mice (Kobayashi et al 2009). Moreover, the plasma concentrations of thyroxine (T4) are significantly lower, while the serum TSH concentrations are markedly elevated, in grt mice than in normal mice (Yoshida et al 1994;Tomita et al 1995;Kobayashi et al 2001).…”

Section: Introductionmentioning

confidence: 99%

“…1994). In addition to this severe postnatal growth retardation, impaired development of growth hormone (GH)‐, prolactin (PRL)‐ and thyroid‐stimulating hormone (TSH)‐producing cells in the pituitary, and altered hormone concentrations of these hormones in the plasma are also observed in grt mice (Kobayashi et al . 2009).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Relationship between growth retardation and impaired glucose tolerance in hypothyroidal growth‐retarded (grt) mice

Tasaki¹,

Taguchi²,

Machida³

et al. 2010

Congenital Anomalies

Self Cite

View full text Add to dashboard Cite

Growth-retarded (grt) mice exhibit congenital hypothyroidism and a characteristic growth pause followed by delayed onset of pubertal growth. This pattern of growth has never been reported in any other animal model exhibiting hypothyroidism; therefore, the growth retardation observed in grt mice is unlikely to be explained completely by the low plasma thyroid hormone levels. As growth is closely related to nutrient metabolism, we investigated the relationship between the appearance of growth retardation and glucose utilization, which is the main component of nutrient metabolism, in the peripubertal stage of grt mice. The relative weights of the organs involved in nutrient digestion and absorption were abnormal in grt mice. The intraperitoneal glucose tolerance test (IGTT) showed impaired glucose tolerance in grt mice. Moreover, this symptom appeared in parallel with the progression of growth retardation in grt mice. The impaired blood glucose levels on the IGTT in grt mice were considered to be attributable to decreased plasma insulin levels rather than to impaired insulin sensitivity. The pattern of anti-insulin antibody staining on sections of pancreatic islets from grt mice was almost the same as that in the corresponding sections from normal mice. Insulin treatment accelerated the growth of peripubertal grt mice. These findings suggest that the appearance of growth retardation in grt mice might be partially attributable to a reduction in glucose metabolism and impairment of insulin secretion during the early period of growth.

show abstract

Gene Expression in Mouse Thyrotrope Adenoma: Transcription Elongation Factor Stimulates Proliferation

et al. 2016

View full text Add to dashboard Cite

Thyrotrope hyperplasia and hypertrophy are common responses to primary hypothyroidism. To understand the genetic regulation of these processes, we studied gene expression changes in the pituitaries of Cga(-/-) mice, which are deficient in the common α-subunit of TSH, LH, and FSH. These mice have thyrotrope hypertrophy and hyperplasia and develop thyrotrope adenoma. We report that cell proliferation is increased, but the expression of most stem cell markers is unchanged. The α-subunit is required for secretion of the glycoprotein hormone β-subunits, and mutants exhibit elevated expression of many genes involved in the unfolded protein response, consistent with dilation and stress of the endoplasmic reticulum. Mutants have elevated expression of transcription factors that are important in thyrotrope function, such as Gata2 and Islet 1, and those that stimulate proliferation, including Nupr1, E2f1, and Etv5. We characterized the expression and function of a novel, overexpressed gene, transcription elongation factor A (SII)-like 5 (Tceal5). Stable expression of Tceal5 in a pituitary progenitor cell line is sufficient to increase cell proliferation. Thus, Tceal5 may act as a proto-oncogene. This study provides a rich resource for comparing pituitary transcriptomes and an analysis of gene expression networks.

show abstract

Impaired Development of Somatotropes, Lactotropes and Thyrotropes in Growth-Retarded (grt) Mice

Cited by 4 publications

References 47 publications

Regenerative Capacity of the Adult Pituitary: Multiple Mechanisms of Lactotrope Restoration After Transgenic Ablation

Regenerative Capacity of the Adult Pituitary: Multiple Mechanisms of Lactotrope Restoration After Transgenic Ablation

Relationship between growth retardation and impaired glucose tolerance in hypothyroidal growth‐retarded (grt) mice

Gene Expression in Mouse Thyrotrope Adenoma: Transcription Elongation Factor Stimulates Proliferation

Contact Info

Product

Resources

About