Restricted expression of somatostatin receptor 3 to primary cilia in the pancreatic islets and adenohypophysis of mice

Iwanaga, Toshihiko; Miki, Takashi; Takahashi-Iwanaga, Hiromi

doi:10.2220/biomedres.32.73

Cited by 43 publications

(37 citation statements)

References 37 publications

(43 reference statements)

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“…The D2R antibody used selectively stained the striatum in the mouse brain (33) but never stained any structures in the adrenal gland or pancreatic islets. SSTR3 and AC3 antibodies used specifically labeled the primary cilia on neurons in several regions of the mouse brain, in agreement with previous studies (24). The specificity of immunoreactions with the anti-D2R antibody was confirmed by disappearance of the immunoreactivity when the antibody was preincubated with a peptide antigen (Frontier Institute Co.Ltd).…”

Section: Animalssupporting

confidence: 88%

“…Electron microscopic studies of these endocrine cells have demonstrated the existence of single cilia which display a structural organization unlike that of the motile cilia (5,45,49). Our recent immunohistochemical study revealed an abundance of SSTR3-expressing solitary cilia in growth hormone (GH)-secreting cells and insulin-secreting β-cells of the mouse (24). Further application of immunostaining for various receptors in the nervous and endocrine tissues holds promise for establishing the primary cilia as universal sensory devices.…”

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confidence: 95%

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Immunohistochemical demonstration of dopamine receptor D2R in the primary cilia of the mouse pituitary gland

2011

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Dopamine regulates the synthesis and secretion of prolactin and α-MSH/β-endorphin in lactotrophs and melanotrophs, respectively. While a predominant dopamine receptor, D2R, is known to be expressed in both the anterior and intermediate lobes of the pituitary gland, no previous immunohistochemical studies have shown the existence of D2R in the plasma membrane of pituitary endocrine cells. The present study clearly demonstrated a selective localization of the D2R immunoreactivity in primary cilia of lactotrophs and melanotrophs in the mouse adenohypophysis. Another immunoreactivity of D2R was found along the plasma membrane of melanotrophs. The intensity of immunoreactivity for D2R in the primary cilia of lactrotrophs changed during the estrous cycle and with genital conditions in contrast to a consistent immunolabeling in the melanotrophs. Since there is accumulating evidence that the primary cilium functions as a sensory device at a cellular level, the D2R-expressing primary cilia in the pituitary gland may be involved in the sensation of dopamine and dopaminergic compounds-though their involvement differs between the anterior and intermediate lobes.Dopamine is well established as a primary inhibitor of both prolactin secretion (6) and the proliferation of lactotrophs (1, 13). Dopamine is released at the median eminence and conveyed by the hypothalamic portal system to regulate the activities of pituitary lactotrophs mainly via the type 2 dopamine receptor (D2R). Accordingly, D2R knockout mice display a phenotype characterized by chronic hyper-prolactinemia and the hyperplasia of lactotrophs (16,25). Although dopamine must exert its actions by binding to specific membrane receptors on pituitary endocrine cells, previous immunohistochemical studies of normal and tumoral lactotrophs have detected D2R immunoreactivities in the cytoplasm but not in the plasma membrane (18,41,48). This is an inconsistent finding concerning the subcellular localization of D2R-though we sometimes experience such a discrepancy with the immunostaining of membrane-bound receptors. The pituitary intermediate lobe is also under the control of dopamine (10)(11)(12)17) and expresses D2R at a high density, unlike the anterior lobe (3). In situ hybridization analyses for D2R mRNA and radioligand binding assays in rats have demonstrated a condensed expression of D2R or dopamine binding sites in the intermediate lobe (28,32,35). The intermediate lobe morphologically differs from the anterior lobe by having rich innervation and poor vascularization (4, 26, 27) and being composed of essentially one type of endocrine cell, melanotrophs. The melanotrophs receive dopamine input from tuberohypophyseal neurons that actually terminate within the intermediate lobe (4). Dopamine has been experimentally shown to decrease the capacity of the intermediate lobe to synthesize pro-opiomelanocortin

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Section: Animalssupporting

confidence: 88%

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confidence: 95%

Immunohistochemical demonstration of dopamine receptor D2R in the primary cilia of the mouse pituitary gland

2011

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“…To investigate ciliary changes in the hypothalamus in mouse models of obesity, cilia were immunostained using an antibody against adenylate cyclase 3 (AC3) (8). Immunohistochemistry for somatostatin receptor 3 (SSTR3), another marker used to identify cilia in neurons (9), labeled only about 30%-50% of AC3-immunoreactive cilia in the hypothalamus (Supplemental Figure 1; supplemental material available online with this article; doi:10.1172/JCI69395DS1). Nevertheless, the complete overlap of AC3 and SSTR3 staining along the entire length of the cilia confirmed that AC3 is a useful marker for analyzing cilia length.…”

Section: Resultsmentioning

confidence: 99%

Leptin-promoted cilia assembly is critical for normal energy balance

et al. 2014

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The majority of mammalian cells have nonmotile primary cilia on their surface that act as antenna-like sensory organelles. Genetic defects that result in ciliary dysfunction are associated with obesity in humans and rodents, which suggests that functional cilia are important for controlling energy balance. Here we demonstrated that neuronal cilia lengths were selectively reduced in hypothalami of obese mice with leptin deficiency and leptin resistance. Treatment of N1 hypothalamic neuron cells with leptin stimulated cilia assembly via inhibition of the tumor suppressors PTEN and glycogen synthase kinase 3β (GSK3β). Induction of short cilia in the hypothalamus of adult mice increased food intake and decreased energy expenditure, leading to a positive energy balance. Moreover, mice with short hypothalamic cilia exhibited attenuated anorectic responses to leptin, insulin, and glucose, which indicates that leptin-induced cilia assembly is essential for sensing these satiety signals by hypothalamic neurons. These data suggest that leptin governs the sensitivity of hypothalamic neurons to metabolic signals by controlling the length of the cell's antenna. IntroductionMost mammalian cells have single nonmotile primary cilia, which were once thought to be vestigial but are now considered to be important signaling centers (1, 2). Accumulating evidence suggests a strong association between genetic ciliopathies and obesity in humans and animals (3). Obesity is a common manifestation observed in human genetic ciliopathies such as Bardet-Biedl syndrome (BBS) and Alström syndrome (4). Mice that lack BBS proteins and ciliary proteins such as the kinesin-2 subunit KIF3A and the intraflagellar transport protein 88 homolog (IFT88) are obese and hyperphagic (5-7). Furthermore, selective depletion of KIF3A in neurons, particularly in anorexigenic proopiomelanocortinproducing (POMC-producing) neurons, yields an obese phenotype (7), which suggests that neuronal cilia play a critical role in the maintenance of energy balance. Based on the association between genetic ciliopathies and obesity (3), we hypothesized that acquired or other types of genetic obesity may accompany ciliary defects in the hypothalamus, a key brain area involved in the sensation of peripheral metabolic signals and the orchestration of whole-body energy metabolism.

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“…Lean mass growth that is driven by growth hormone is regulated by hypothalamic hormones, including somatostatin (38). Somatostatin receptor 3 (SSR3) is localized to the primary cilium (39), and its function may be affected by RPGRIP1L action. It is plausible that RPGRIP1L action in hypothalamic cilia may also regulate body growth through effects on SSR3.…”

Section: Discussionmentioning

confidence: 99%