Regression of redundant lactotrophs in rat pituitary gland after cessation of lactation

Haggi, E.; Torres, Alicia Inés; Maldonado, Cristina A.; Aoki, Agustı́n

doi:10.1677/joe.0.1110367

Cited by 67 publications

(43 citation statements)

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“…gestation, and lactancy (22,47). This hormone output must be fine-tuned and adapt swiftly to changing needs, thereby requiring dynamic and accurate functional and quantitative remodeling of the hormonal cells (36,45).…”

mentioning

confidence: 99%

The expansion of adult stem/progenitor cells and their marker expression fluctuations are linked with pituitary plastic adaptation during gestation and lactancy

Vaca

Guido

Sosa

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

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Extensive evidence has revealed variations in the number of hormone-producing cells in the pituitary gland, which occur under physiological conditions such as gestation and lactancy. It has been proposed that new hormone-producing cells differentiate from stem cells. However, exactly how and when this takes place is not clear. In this work, we used immunoelectron microscopy to identify adult pituitary stem/progenitor cells (SC/P) localized in the marginal zone (MZ), and additionally, we detected GFRa2-, Sox2-, and Sox9-positive cells in the adenoparenchyma (AP) by fluorescence microscopy. Then, we evaluated fluctuations of SC/P mRNA and protein level markers in MZ and AP during gestation and lactancy. An upregulation in stemness markers was shown at term of gestation (AT) in MZ, whereas there were more progenitor cell markers in the middle of gestation and active lactancy. Concerning committed cell markers, we detected a rise in AP at beginning of lactancy (d1L). We performed a BrdU uptake analysis in MZ and AP cells. The highest level of BrdU uptake was observed in MZ AT cells, whereas in AP this was detected in d1L, followed by a decrease in both the MZ and AP. Finally, we detected double immunostaining for BrdU-GFRa2 in MZ AT cells and BrdU-Sox9 in the AP d1L cells. Taken together, we hypothesize that the expansion of the SC/P niche took place mainly in MZ from pituitary rats in AT and d1L. These results suggest that the SC niche actively participates in pituitary plasticity during these reproductive states, contributing to the origin of hormone cell populations.

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confidence: 99%

The expansion of adult stem/progenitor cells and their marker expression fluctuations are linked with pituitary plastic adaptation during gestation and lactancy

Vaca

Guido

Sosa

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

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“…Further, the relationship of altered prolactin secretion to lactotroph proliferation is also unclear. Pregnancy induces a coordinated increase in prolactin release and the number of lactotrophs, with a marked involution in their number once lactation ceases (1)(2)(3)(4). In contrast, a sustained and uncontrolled proliferation of lactotrophs culminates in the development of prolactin-secreting adenomas (prolactinomas) resulting in inappropriate lactation.…”

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confidence: 99%

Galanin regulates prolactin release and lactotroph proliferation

Wynick

Small

Bacon

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

187

138

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The neuropeptide galanin is predominantly expressed by the lactotrophs (the prolactin secreting cell type) in the rodent anterior pituitary and in the median eminence and paraventricular nucleus of the hypothalamus. Prolactin and galanin colocalize in the same secretory granule, the expression of both proteins is extremely sensitive to the estrogen status of the animal. The administration of estradiol-17␤ induces pituitary hyperplasia followed by adenoma formation and causes a 3,000-fold increase in the galanin mRNA content of the lactotroph. To further study the role of galanin in prolactin release and lactotroph growth we now report the generation of mice carrying a loss-of-function mutation of the endogenous galanin gene. There is no evidence of embryonic lethality and the mutant mice grow normally. The specific endocrine abnormalities identified to date, relate to the expression of prolactin. Pituitary prolactin message levels and protein content of adult female mutant mice are reduced by 30-40% compared with wild-type controls. Mutant females fail to lactate and pups die of starvation͞dehydration unless fostered onto wild-type mothers. Prolactin secretion in mutant females is markedly reduced at 7 days postpartum compared with wild-type controls with an associated failure in mammary gland maturation. There is an almost complete abrogation of the proliferative response of the lactotroph to high doses of estrogen, with a failure to up-regulate prolactin release, STAT5 expression or to increase pituitary cell number. These data further support the hypothesis that galanin acts as a paracrine regulator of prolactin expression and as a growth factor to the lactotroph.The factors that regulate proliferation of the lactotroph are largely unknown. Further, the relationship of altered prolactin secretion to lactotroph proliferation is also unclear. Pregnancy induces a coordinated increase in prolactin release and the number of lactotrophs, with a marked involution in their number once lactation ceases (1-4). In contrast, a sustained and uncontrolled proliferation of lactotrophs culminates in the development of prolactin-secreting adenomas (prolactinomas) resulting in inappropriate lactation. The prevalence of prolactinomas is an estimated 100 per million (5). However, in autopsy series of elderly females the prevalence is 1,000-fold greater, emphasizing that most prolactinomas are clinically silent and common in the elderly population (6). Prolactinomas are also a common cause of death in female aged rats of a number of strains (7-9). Treatment of prolactinomas with dopamine agonists reduces pituitary prolactin expression and reverses lactotroph hyperplasia, emphasizing the link between prolactin expression and cellular proliferation. Prolactinomas arise as monoclonal neoplasms, indicating that one or more somatic mutations underlie tumor pathogenesis. A large and increasing body of literature has failed to identify mutations in known protooncogenes in human prolactinomas (10-12). In contrast, exogenous estro...

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“…As a prominent example, the number (and activity) of lactotropes rises during pregnancy and lactation to meet the heightened demand for PRL (Haggi et al 1986;Vankelecom 2012). This expansion is at least partly due to elevated estrogen levels in these conditions.…”

Section: Plastic Cell Adaptationsmentioning

confidence: 99%

Pituitary Stem Cells: Quest for Hidden Functions

Vankelecom

2016

Stem Cells in Neuroendocrinology

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The pituitary is the core endocrine gland, ruling fundamental processes of body growth, metabolism, reproduction and stress. Over the past decade, it has progressively become clear that the pituitary, like many adult tissues, harbors a population of stem cells. While the molecular depiction of these cells is constantly expanding, their function remains essentially hidden. From recent studies, the picture is developing that the stem cells of the adult pituitary are highly quiescent and mainly come into play during pathological conditions.Upon transgenic cell-ablation damage in the pituitary, the stem cell compartment is promptly turned on with expansion and expression of the missing hormone. This activation is accompanied by substantial regeneration of the lost hormonal cells, a restorative competence that was unexpected in the mature gland. This regenerative skill, however, rapidly disappears with aging, together with a decline in the number and fitness of the stem cells. One function of the adult pituitary stem cells may thus be hidden in the regenerative toolbox of the gland, at least during a specified and limited time window.Recent work also showed activation of the pituitary stem cell compartment during tumor formation in the (mouse) gland. Moreover, pituitary tumors (from patients and mice) contain a candidate 'tumor stem cell' (TSC) population. The pathogenetic steps of initiation, expansion, invasion and recurrence of pituitary tumors remain far from understood. A link between the tumor-driving TSC and the pituitary stem cells may shed new light on this tumorigenic darkness.To conclude, decoding the hidden functions of pituitary stem cells will not only lead to better fundamental insights into their role but may also expose (novel) targets for treating pituitary tumors and for regenerative intervention in pituitary deficiency, as caused by damage, tumors or aging. Yet, the journey in the 'hidden valley' of pituitary stem cell functions has only just begun, and a long distance still has to be walked.

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Regression of redundant lactotrophs in rat pituitary gland after cessation of lactation

Cited by 67 publications

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The expansion of adult stem/progenitor cells and their marker expression fluctuations are linked with pituitary plastic adaptation during gestation and lactancy

The expansion of adult stem/progenitor cells and their marker expression fluctuations are linked with pituitary plastic adaptation during gestation and lactancy

Galanin regulates prolactin release and lactotroph proliferation

Pituitary Stem Cells: Quest for Hidden Functions

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