Physiological implications of pituitary trophic activity

Abstract

A complete inventory of pituitary trophic responses depends on precise estimates of mitotic activity and apoptotic events, and accurate characterization and quantification of pituitary cell subtypes irrespective of previous and current physiological demand. For a discrete structure that has been so extensively studied, it is disappointing but perhaps not surprising that none of these measures is available and therefore that the relative contributions to changes in the proportions of pituitary cellular subpopulations of trophic activity, differentiation of pluripotent cells and variations in the secretory profiles of apparently committed cells remain almost impossible to determine. To fully appreciate the extent of this dilemma, it should be remembered that conservative estimates of the proportion of corticotrophs in the rat anterior pituitary under basal conditions vary over twofold and that it is still not clear whether the apparent threefold increase in mammotrophs during pregnancy is the result of maturation of uncommitted cells, transdifferentiation of other cells such as somatotrophs, cell division, or a mixture of all three. Equally, while it has been known for some time that adrenalectomy results in a transient increase in anterior pituitary mitotic activity and appropriately timed supraphysiological glucocorticoid replacement with a wave of apoptosis, the precise identity of the cells involved in both of these responses is open to question. Thus, although many of the physiological stimuli associated with apparent changes in the proportions of pituitary cellular subpopulations are known, the precise mechanism of the changes and the consequences of the same remain obscure. This review summarizes the limited literature on pituitary trophic activity and asks what, if anything, analysis of pituitary trophic activity using current technology can tell us.

FOXL2 versus SOX9: A lifelong “battle of the sexes”

“…It would be interesting to explore the transcriptome (and, more interestingly, the proteome) of follicular cells in the period when neither Foxl2 nor Sox9 are expressed, in order to assess whether these cells are temporarily ''bifunctional,'' as proposed in cases of transdifferentiation in the context of pituitary cell lineages. [43][44][45] This would still be compatible with the idea of toggle switch, because a proteomic switch should take some time (i.e., synthesis of new proteins and decay of old ones). Transdifferentiation has been proposed to occur in the pituitary.…”

“…Transdifferentiation has been proposed to occur in the pituitary. [44] For instance, induced hypothyroidism in adult rats leads to a reduced number of somatotroph cells that are gradually ''replaced'' by thyrotrophs, which share the same precursor. Co-expression of GH and TSH in the same cell and a reduction of GH signal in somatotrophs suggest that the increased number of TSH cells results, at least in part, from the transdifferentiation of somatotrophs.…”

The role of SOX proteins in normal pituitary development

“…The doubling of the number of somatotrophs during puberty as well as the expansion and contraction of lactotrophs during lactation and weaning are examples of the plasticity of the gland (Sasaki 1988, Levy 2002.…”

Pituitary Stem Cells: Quest for Hidden Functions

“…Other organs are more static in their cell composition and only need cell replacement at a very low pace (such as the brain, heart, liver, pancreas, lung; Alvarez-Buylla and Lim 2004; Barker et al 2010;Huch et al 2013a,b;Rando 2006;Slack 2008;Vankelecom 2012;Wabik and Jones 2015). The pituitary belongs to the latter group, undergoing turnover in terms of months rather than days (Levy 2002(Levy , 2008Nolan et al 1998;Rando 2006;Vankelecom 2012;Vankelecom and Chen 2014). Stem cells in organs with low turnover appear highly dormant (quiescent) and are only jolted awake by strong triggers like loss of cells by damage.…”

“…Adrenalectomy causes a swift, transient rise in corticotropes, whereas gonadectomy triggers a fast and transitory increase in gonadotropes. Previous studies provided circumstantial evidence that 'hormonally null cells' (the at that time postulated pituitary stem cells) contribute to the new corticotropes and gonadotropes (Levy 2002(Levy , 2008Nolan et al 1998;Nolan and Levy 2006). Recent studies provided more direct evidence that pituitary stem cells are involved.…”