A Population of Non‐Luteinising Hormone/Non‐Adrenocorticotrophic Hormone‐Positive Cells in the Male Rat Anterior Pituitary Responds Mitotically to Both Gonadectomy and Adrenalectomy

Abstract

The male rat anterior pituitary responds highly reproducibly to specific hormonal stimuli in terms of the extent and timing of mitotic and apoptotic (trophic) activity. The principal objective of the present study was to define the contribution of hormonally identifiable cells to the trophic responses to bilateral gonadectomy and bilateral adrenalectomy. The patterns of pituitary mitotic responses to adrenalectomy and gonadectomy are similar in amplitude and duration. When adrenalectomy and gonadectomy are combined, the amplitude of the pituitary mitotic response is unchanged. That is, the trophic stimuli are not additive. Dexamethasone-induced apoptosis in nascent cells is amplified not only by recent adrenalectomy, but also, and to an almost identical extent, by gonadectomy. Combining adrenalectomy and gonadectomy does not further enhance the size of the apoptotically-responsive cell population. Dual bromodeoxyuridine and adrenocorticotrophic hormone (ACTH) or luteinising hormone (LH) immunolabelling showed that more than 95% of all dividing cells are not and do not become positive for either of these hormones during the period of peak mitotic response. Following adrenalectomy, most newly-formed ACTH cells are derived from differentiation of pre-existing hormonally undifferentiated cells. Despite an overall increase in mitotic activity, there is no measurable increase in the number of LH immunopositive cells after gonadectomy. The nonadditive pituitary mitotic and apoptotic responses to adrenalectomy and gonadectomy strongly suggest that the same progenitor cell population responds mitotically to both. This weakens the prevailing view that hormonally identifiable cells with specific trophic profiles contribute significantly to pituitary cell subpopulation revision.

The parvocellular vasopressinergic system and responsiveness of the hypothalamic pituitary adrenal axis during chronic stress

“…Other studies have also shown lack of co-localization of BrdU in corticotrophs following adrenalectomy (Gulyas et al, 1991;Nolan & Levy, 2001;Taniguchi et al, 1995). Nolan and Levy, (Nolan & Levy, 2006) also reported a minor incidence of mitogenesis in corticotrophs or gonadotrophs following 3-and 6-days adrenalectomy or gonadectomy in rats. In the latter study, there was no additivity of mitogenic responses to adrenalectomy and gonadectomy, supporting the view that mitogenesis in response to both stimuli occurs in an undifferentiated progenitor population (Nolan & Levy, 2006).…”

SOX2-expressing progenitor cells generate all of the major cell types in the adult mouse pituitary gland

“…The mechanisms underlying these changes are poorly understood. Fluctuations in the rate of cell division and cell death in the differentiated endocrine cell populations could explain some of the changes, but direct studies of the pituitary mitotic responses after stimuli that increase the number of ACTH and LH cells show that these changes do not arise by cell division from mature endocrine cells but rather by differentiation from uncommitted progenitors (6). Furthermore, it is difficult to explain the remarkable ability of the adult pituitary gland to repopulate after extreme loss of specific cell populations by genetic (7) or immune (8) lesions without the involvement of a multipotent stem or progenitor population in the adult gland (reviewed in refs.…”

Perspective on Stem Cells in Developmental Biology, with Special Reference to Neuroendocrine Systems

“…While differentiated endocrine cells can divide, but do so rarely, Nolan and Levy were the first to observe that, after adrenalectomy and/or gonadectomy, proliferation is essentially restricted to non-endocrine cells of an immature appearance. Moreover, double ablations do not have an additive proliferative effect, suggesting that a single population of undifferentiated cells responds to both adrenalectomy and gonadectomy (Nolan and Levy 2006). More recently, diphtheria toxin-mediated endocrine cell ablation experiments confirmed these results by showing a mobilization of SOX2-positive cells, with a transient induction of proliferation and, presumably, differentiation.…”

“…Induction of apoptosis upon cell division, using specific genetic tools, confirmed this hypothesis by demonstrating that corticotroph turnover relies on the proliferation of differentiated cells (Langlais et al 2013). A physiological role for pituitary stem cells was initially suggested by studies investigating models of pituitary target organ ablation (Nolan and Levy 2006). It has been known for some time that ablation of the adrenals and/or gonads triggered a transient mitotic wave in the gland, followed by generation of increased numbers of endocrine cells; moreover, these were specifically the type that normally regulates the ablated organ.…”