Effects of Hypothalamic Lesions and Drugs Interfering with Dopaminergic Transmission on Pituitary MSH Content of Rats

Tilders, F. J. H.; Smelik, P. G.

doi:10.1159/000122748

Cited by 37 publications

(16 citation statements)

References 8 publications

(9 reference statements)

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“…For immunohistochemistry, mice were perfused with a physiological saline through the heart, followed by 4% paraformaldehyde plus 0.2% picric acid in 0.1 M phosphate buf-(POMC) and release its products: α-melanocytestimulating hormone (α-MSH) and β-endorphin (12,14,43,44). It is known that dopaminergic compounds differentially control the D2R mRNA levels and activities of target endocrine cells in two lobes of the rat pituitary gland (3,10).…”

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confidence: 99%

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

2011

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“…The secretion of the pars intermedia peptides, alpha-MSH and beta-endorphin, is subject to an inhibitory control by the tubero-hypophyseal dopamine system, as demon strated by in vitro and in vivo studies [9,25,51]. These dopamine neurons, in turn, respond to feedback actions of alpha-MSH [28].…”

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Early Postnatal Development of Pituitary Intermediate Lobe Control in the Rat by Dopamine Neurons

et al. 1984

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In fetal and postnatal rats, serum melanophore-stimulating hormone (MSH) levels, pituitary ³H-spiperone binding, pituitary catecholamine content, and other parameters were measured to characterize the development of pars intermedia pituitary control by the tubero-hypophyseal dopamine system. Bioassay of serum for MSH revealed low but significant levels 6 days before birth (gestational day 17), rising to a peak 4 days after birth (postnatal day 5). Levels declined after PN 6, reached a low 2 weeks after birth, and then rose gradually throughout the next several weeks until adult values were attained. From excised pituitaries, significant catecholamine fluorescence in the neurointermediate lobe was first demonstrated on the 2nd postnatal day, with the highest density of fibers being attained at 2 weeks after birth. Thereafter, the density of terminals decreased in the pars intermedia until the adult pattern of innervation was observed at day 60. Total dopamine content of the neurointermediate lobe roughly paralleled the morphological observations through the first 2 weeks after birth. Later, content was seen to stabilize, while concentration decreased in line with the reduction in terminal density. Dopamine levels exceeded norepinephrine concentration by a factor of 10. ³H-spiperone binding sites were present in the pituitary before birth. Their density increased rapidly in the neurointermediate lobe during the first 2 postnatal weeks, then diminished until adult densities were reached at day 30. Binding in the anterior pituitary slowly rose throughout the first 30 days after birth, although values were only about one-quarter of that found in the neurointermediate lobe. In vitro incubation of neurointermediate lobes with dopamine showed a dose-dependent inhibition of spontaneous MSH secretion as early as 2 days after birth. Blockade of dopaminergic binding sites by i.p. administration of cis-flupenthixol (1 mg/kg) to rat pups had no effect until days 8, 15, and 22 where there was a significant rise in serum MSH levels as compared with controls. These data indicate that the intermediate lobe is responsive to dopamine at around birth, while the inhibitory dopaminergic control develops only during the 1st postnatal week, in conjunction with marked changes in circulating MSH levels.

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“…Penny and Thody [II] and Tilders and Smelik [19] could not detect changes in the pitu itary hormone content after CB-154 adminis tration in intact rats. The apparent discre pancy between our results and previous work might be due to the fact that they administered the drug acutely, whereas we administered it chronically.…”

Section: Discussionmentioning

confidence: 99%

“…One approach to testing this hypothesis was to inhibit MSH secretion and observe changes in the normal develop ment of the coat color. Ergocryptine was cho sen for this study, since it has been reported to inhibit the secretion of MSH [11,16,19].…”

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Alteration of the Agouti Mouse Coat Color Pattern by Bromoergocryptine. Possible Involvement of MSH

Levitin¹,

Dumm²,

Iturriza³

1979

Neuroendocrinology

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In the Agouti mice C3H A" the coat color of the dorsum changes from birth to maturity. In young animals the dorsal tegument is yellow whereas in adult mice it shifts to dark gray. The administration of bromoergocryptine, a dopamine agonist, as a single injection in a beeswax pellet prevented the color change resulting in the persistence of the immature pattern. After plucking an area of the dorsum of an adult animal, the regrown hair was dark; however, when bromoergocryptine was administered at the time of plucking the new hair was not dark but yellow. When MSH was injected in adult animals previously treated with the drug, the ‘bleaching’ effect of bromoergocryptine was abolished, suggesting that this substance did not act directly upon melanin synthesis. In bromoergocryptine-treated mice the MSH content of the pars intermedia was decreased and the ultrastructure of this lobe contained cells with signs of hypoactivity. These two observations suggested that the effect of the drug on the coat color might be ascribed to inhibition of the secretion of MSH.

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Effects of Hypothalamic Lesions and Drugs Interfering with Dopaminergic Transmission on Pituitary MSH Content of Rats

Cited by 37 publications

References 8 publications

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

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

Early Postnatal Development of Pituitary Intermediate Lobe Control in the Rat by Dopamine Neurons

Alteration of the Agouti Mouse Coat Color Pattern by Bromoergocryptine. Possible Involvement of MSH

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