Anterior pituitary thyrotropes are multifunctional cells

Abstract

Anterior pituitary (AP) contains some unorthodox multifunctional cells that store and secrete two different AP hormones (polyhormonal cells) and/or respond to several hypothalamic-releasing hormones (HRHs; multiresponsive cells). Multifunctional cells may be involved in paradoxical secretion (secretion of a given AP hormone evoked by a noncorresponding HRH) and transdifferentiation (phenotypic switch between different mature cell types without cell division). Here we combine calcium imaging (to assess responses to the four HRHs) and multiple sequential immunoassay of the six AP hormones to perform a single-cell phenotypic study of thyrotropes in normal male and female mice. Surprisingly, most of the thyrotropes were polyhormonal, containing, in addition to thyrotropin (TSH), luteinizing hormone (40 -42%) and prolactin (19 -21%). Thyrotropes costoring growth hormone and/or ACTH were found only in females (24% of each type). These results suggest that costorage of the different hormones does not happen at random and that gender favors certain hormone combinations. Our results indicate that thyrotropes are a mosaic of cell phenotypes rather than a single cell type. The striking promiscuity of TSH storage should originate considerable mix-up of AP hormone secretions on stimulation of thyrotropes. However, response to thyrotropin-releasing hormone was much weaker in the polyhormonal thyrotropes than in the monohormonal ones. This would limit the appearance of paradoxical secretion under physiological conditions and suggests that timing of hormone and HRH receptor expression during the transdifferentiation process is finely and differentially regulated. anterior pituitary; hypothalamic releasing factors; paradoxical secretion THE ANTERIOR PITUITARY (AP) contains five main cell types, somatotropes, mammotropes, corticotropes, thyrotropes, and gonadotropes, which secrete growth hormone (GH), prolactin (PRL), ACTH, thyrotropin (TSH), and gonadotropins [follicle-stimulating hormone (FSH) and luteinizing hormone (LH)], respectively. Thyrotropes are the least abundant cell type, amounting to ϳ5-8% of all the AP cells. However, this cell type plays a pivotal role in control of metabolism through regulation of thyroid activity. In the classic view, each AP cell type stores a single hormone in which secretion is specifically regulated by a particular hypothalamic-releasing hormone (HRH). Thus thyrotropes are believed to store and release TSH and express functional thyrotropin-releasing hormone (TRH) receptors involved in hypothalamic control of TSH secretion. However, in the last decade, this "one cell-one hormone" hypothesis has been challenged repeatedly. It has been reported, for example, that many pituitary cells may store and release more than one AP hormone. Mammosomatotropes that store and release GH and PRL (13) have been regarded as an intermediate stage for conversion of somatotropes into mammotropes, a phenotypic switch between mature cell types without cell division called transdifferentiation (13, 31). Polyhormona...

Cells Co-Expressing Luteinising Hormone and Thyroid-Stimulating Hormone Are Present in the Ovine Pituitary Pars Distalis but Not the Pars Tuberalis: Implications for the Control of Endogenous Circannual Rhythms of Prolactin

“…This corroborates previous studies in BS ewes and in mice, and highlights a species difference in the prevalence of co-expression, as in contrast to sheep which showed a 10% co-expression in the PD [34], almost 41% of the mouse thyrotrophs were found to co-express LHB protein and secrete LH [35]. Whilst historically such cells are considered to represent an intermediate step in the trans-differentiation process, they are observed in the normal, resting gland where the rate of trans-differentiation is low.…”

“…Therefore, LHB/TSHB bihormonal cells may provide the morphological basis for the observation that TRH stimulates LH secretion in humans [36]. Although this could equally be due to a paracrine interaction between neighbouring thyrotrophs and gonadotrophs, application of TRH evokes increases in intracellular calcium concentrations in cells co-expressing LHB and TSHB, suggesting the presence of an intact TRHR in these bi-hormonal cells [35]. …”

Characterization of Xenobiotic-Induced Hepatocellular Enzyme Induction in Rats

“…Thyrotroph hypertrophy was not associated with increased mitotic activity or a change in the total number of thyrotrophs, suggesting there was no progression to hyperplasia at fourteen days. Thus, as demonstrated in this study, individual cells of the anterior pituitary demonstrate an inherent plasticity to adapt to physiologic demands to which males may be more sensitive than females (Senovilla et al 2008;Vankelecom 2007;Villalobos et al 2004), such as induction of hepatic enzymes and subsequent alterations in thyroid hormone homeostasis. Vol.…”

Central Ghrelin Affects Pituitary-Thyroid Axis: Histomorphological and Hormonal Study in Rats

“…Therefore, it is possible that ghrelin treatment could promote transdifferentiation of a multiresponsive and polyhormonal TSH cell subpopulation [43, 44] to GH and/or PRL cells, thus contributing to the decrease in volume density of pituitary thyrotrophs detected under our experimental conditions. Further double immunostaining studies are needed to confirm this hypothesis.…”