Thyroid Hormone Is Essential for Pituitary Somatotropes and Lactotropes*

Stahl, J; Kendall, Susan; Brinkmeier, Michelle L.; Greco, Tamara L.; Watkins‐Chow, Dawn E.; Campos‐Barros, Ángel; Lloyd, Ricardo V.; Camper, Sally A.

doi:10.1210/endo.140.4.6627

Cited by 43 publications

(28 citation statements)

References 50 publications

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“…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

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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.

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“…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

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“…The two cell populations most heavily affected are the lactotrophic cells, which are almost undetectable in Pax8 Ϫ/Ϫ pituitaries, and the thyrotrophic cells, which exhibit severe hypertrophy and hyperplasia (9). Similar observations have been made in the pituitaries of other hypothyroid animal models such as the glycoprotein hormone ␣-subunit Ϫ/Ϫ (␣GSU Ϫ/Ϫ ) and the hyt/hyt mouse (10,11).…”

supporting

confidence: 65%

Analysis of Hypertrophic Thyrotrophs in Pituitaries of Athyroid Pax8−/− Mice

et al. 2009

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Thyroid hormone is important for pituitary development and maintenance. We previously reported that in the Pax8(-/-) mouse model of congenital hypothyroidism, lactotrophs are almost undetectable, whereas the thyrotrophs exhibit hyperplasia and hypertrophy. Because the latter might be caused by an overstimulation of thyrotrophs with TRH, we analyzed TRH-R1(-/-)Pax8(-/-) double-knockout mice, which miss a functional thyroid gland and the TRH transducing receptor-1 at pituitary target sites. Interestingly, in these double mutants, the hypertrophy and hyperplasia of the thyrotrophs still persist, suggesting that the phenotype is rather a direct consequence of the athyroidism of the animals. The increased expression of TSH in the Pax8(-/-) mice was paralleled by a strongly up-regulated expression of deiodinase type 2 (Dio2) in thyrotrophic cells. Moreover, coexpression of TSH and Dio2 could also be demonstrated in the pituitary of wild-type mice, underlining the important role of this enzyme in the negative feedback regulation of TSH by thyroid hormone. As another consequence of the athyroidism in the mutant mice, tyrosine hydroxylase mRNA expression was found to be also highly up-regulated in thyrotrophic cells of the pituitaries from Pax8(-/-) mice, whereas the transcript levels in the hypothalamus were not affected. Accordingly, tyrosine hydroxylase protein levels, enzyme activities, and ultimately dopamine concentrations were found to be strongly increased in the pituitaries of Pax8(-/-) mice compared with wild-type animals. These findings may explain in part the reduced number of lactotrophs found in the pituitary of athyroid Pax8(-/-) mice and suggest a novel paracrine regulatory mechanism of lactotroph activity.

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“…The percentage of somatotropes in the adult pituitary varies from 20% to 49%, depending on the species and the sex of the animal: bovine 20-25% [40], porcine 40% [40] , mouse 49% [41], chicken 13-20% [42,43]. Clearly, the precise percentage is dynamic.…”

Section: Discussionmentioning

confidence: 99%