Paracrinicity: The Story of 30 Years of Cellular Pituitary Crosstalk

Abstract

Living organisms represent, in essence, dynamic interactions of high complexity between membrane‐separated compartments that cannot exist on their own, but reach behaviour in co‐ordination. In multicellular organisms, there must be communication and co‐ordination between individual cells and cell groups to achieve appropriate behaviour of the system. Depending on the mode of signal transportation and the target, intercellular communication is neuronal, hormonal, paracrine or juxtacrine. Cell signalling can also be self‐targeting or autocrine. Although the notion of paracrine and autocrine signalling was already suggested more than 100 years ago, it is only during the last 30 years that these mechanisms have been characterised. In the anterior pituitary, paracrine communication and autocrine loops that operate during fetal and postnatal development in mammals and lower vertebrates have been shown in all hormonal cell types and in folliculo‐stellate cells. More than 100 compounds have been identified that have, or may have, paracrine or autocrine actions. They include the neurotransmitters acetylcholine and γ‐aminobutyric acid, peptides such as vasoactive intestinal peptide, galanin, endothelins, calcitonin, neuromedin B and melanocortins, growth factors of the epidermal growth factor, fibroblast growth factor, nerve growth factor and transforming growth factor‐β families, cytokines, tissue factors such as annexin‐1 and follistatin, hormones, nitric oxide, purines, retinoids and fatty acid derivatives. In addition, connective tissue cells, endothelial cells and vascular pericytes may influence paracrinicity by delivering growth factors, cytokines, heparan sulphate proteoglycans and proteases. Basement membranes may influence paracrine signalling through the binding of signalling molecules to heparan sulphate proteoglycans. Paracrine/autocrine actions are highly context‐dependent. They are turned on/off when hormonal outputs need to be adapted to changing demands of the organism, such as during reproduction, stress, inflammation, starvation and circadian rhythms. Specificity and selectivity in autocrine/paracrine interactions may rely on microanatomical specialisations, functional compartmentalisation in receptor–ligand distribution and the non‐equilibrium dynamics of the receptor–ligand interactions in the loops.

Structure and biochemical analysis of the heparin-induced E1 dimer of the amyloid precursor protein

“…The interaction with HSPGs should also dimerize such soluble species that are reported to participate in axonal growth (34) and axonal pruning (36). They might also dimerize with membrane-bound APP and ECM binding of soluble forms could increase the local concentration of secreted APP leading to a modulation of its function as demonstrated, e.g., for growth factors (41).…”

An unusual presentation of acquired hypothyroidism: the Van Wyk–Grumbach syndrome

“…In addition, elevated oestrogen concentrations reduce prolactin inhibitory factor via a negative feedback mechanism, causing a further increase in prolactin (8,33). Prolactin is known to suppress pituitary gonadotropins by slowing GnRH pulse frequency (34,35,36). Slow GnRH pulses preferentially lead to suppression of LH and production of FSH (37).…”

Characterization of adherens junction protein expression and localization in pituitary cell networks

“…The pituitary harbors several types of endocrine cells that release their hormone pulses into the systemic blood circulation, with intermingled supportive folliculo-stellate (FS) cells. For many years, two-dimensional histological studies on pituitary sections showed a heterogeneously scattered distribution of endocrine cells throughout the parenchyma, although specific topographic affinities between heterotypical and homotypical hormone-producing cells have been reported (Allaerts et al 1991, Noda et al 2001, Denef 2008. Pituitary cellular organization is now known to be much more ordered than was traditionally recognized.…”