Mechanisms for pituitary tumorigenesis: the plastic pituitary

Abstract

The anterior pituitary gland integrates the repertoire of hormonal signals controlling thyroid, adrenal, reproductive, and growth functions. The gland responds to complex central and peripheral signals by trophic hormone secretion and by undergoing reversible plastic changes in cell growth leading to hyperplasia, involution, or benign adenomas arising from functional pituitary cells. Discussed herein are the mechanisms underlying hereditary pituitary hypoplasia, reversible pituitary hyperplasia, excess hormone production, and tumor initiation and promotion associated with normal and abnormal pituitary differentiation in health and disease.

Stem Cells in the Postnatal Pituitary?

“…Growth is mainly due to an increase in cell number and size. Between 10 and 30% of the proliferating cells contain hormone immunoreactivity (as studied in the rat) [[7, 8, 20, 23, 28, 31], and references therein], indicating that only part of the new hormonal cells develop by ‘self-mitosis’ of already differentiated cells. This finding further implies that most mitotic activity takes place in undifferentiated cells, and it has repeatedly been suggested that the cells that form shortly after birth, are produced by recruitment (proliferation and differentiation) of stem cells [7, 20, 21, 23, 29].…”

“…Possible mechanisms for cell genesis, as applicable to all tissues, include mitosis of already differentiated cells, transdifferentiation between distinct cell phenotypes, and maturation (differentiation) of stem and progenitor cells. All three processes have in the pituitary field their advocates, and all are supported, although most of the time only circumstantially, by literature data [[5,6,7,8,9,10,11,12,13,14,15,16,17,18], and references therein]. Most likely, all three processes combine their effects in dynamic cell adaptations, but a single mechanism may predominate depending on the particular (patho-)physiological situation.…”

“…Plasticity indeed is one of the cardinal features of the anterior pituitary. The cellular constitution of the mature gland can flexibly change in order to meet the fluctuating hormonal needs of the organism, both with respect to relative or absolute number of cells, and to their synthetic and secretory activity [reviewed in [5,6,7,8]]. The pituitary is made up of the major hormone-producing anterior lobe and the neuro-intermediate part.…”

“…Classically, one distinguishes lactotropes that generate prolactin (PRL), somatotropes that make growth hormone (GH), corticotropes that produce adrenocorticotropic hormone (ACTH), thyrotropes that secrete thyroid-stimulating hormone (TSH), and gonadotropes that produce luteinizing hormone (LH) and/or follicle-stimulating hormone (FSH). One eye-catching example of pituitary plasticity is the 3-fold increase in lactotropes during pregnancy and lactation when high levels of PRL are needed [[5, 7, 8], and references therein]. Despite the long-standing study of the pituitary and the extensive knowledge on the embryonic development of its cell lineages, mechanisms underlying the formation of new hormone-producing cells during plastic cell adaptations in the postnatal gland remain far from understood [5,7,8,9].…”

“…One eye-catching example of pituitary plasticity is the 3-fold increase in lactotropes during pregnancy and lactation when high levels of PRL are needed [[5, 7, 8], and references therein]. Despite the long-standing study of the pituitary and the extensive knowledge on the embryonic development of its cell lineages, mechanisms underlying the formation of new hormone-producing cells during plastic cell adaptations in the postnatal gland remain far from understood [5,7,8,9]. Possible mechanisms for cell genesis, as applicable to all tissues, include mitosis of already differentiated cells, transdifferentiation between distinct cell phenotypes, and maturation (differentiation) of stem and progenitor cells.…”