Regulation of secretory granule formation in chronically hypersecretory melanotrophs in the rat pituitary

Back, Nathan; Soinila, Seppo

doi:10.1007/bf00319432

Cited by 9 publications

(4 citation statements)

References 37 publications

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“…In rat melanotrophs, dopamine regulates secretion by inhibiting adenylyl cyclase activity (391). Bromocriptine, a dopamine D 2 agonist, reduces the size of secretory granules in melanotrophs (20), while haloperidol, a dopamine antagonist, increases the size (21). Thus cAMP might promote hormone secretion by enlarging the size of the secretory granules.…”

Section: B Pituitary Cellsmentioning

confidence: 97%

PKA-Dependent and PKA-Independent Pathways for cAMP-Regulated Exocytosis

Seino¹,

Shibasaki²

2005

Physiological Reviews

518

447

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Stimulus-secretion coupling is an essential process in secretory cells in which regulated exocytosis occurs, including neuronal, neuroendocrine, endocrine, and exocrine cells. While an increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) is the principal signal, other intracellular signals also are important in regulated exocytosis. In particular, the cAMP signaling system is well known to regulate and modulate exocytosis in a variety of secretory cells. Until recently, it was generally thought that the effects of cAMP in regulated exocytosis are mediated by activation of cAMP-dependent protein kinase (PKA), a major cAMP target, followed by phosphorylation of the relevant proteins. Although the involvement of PKA-independent mechanisms has been suggested in cAMP-regulated exocytosis by pharmacological approaches, the molecular mechanisms are unknown. Newly discovered cAMP-GEF/Epac, which belongs to the cAMP-binding protein family, exhibits guanine nucleotide exchange factor activities and exerts diverse effects on cellular functions including hormone/transmitter secretion, cell adhesion, and intracellular Ca(2+) mobilization. cAMP-GEF/Epac mediates the PKA-independent effects on cAMP-regulated exocytosis. Thus cAMP regulates and modulates exocytosis by coordinating both PKA-dependent and PKA-independent mechanisms. Localization of cAMP within intracellular compartments (cAMP compartmentation or compartmentalization) may be a key mechanism underlying the distinct effects of cAMP in different domains of the cell.

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Section: B Pituitary Cellsmentioning

confidence: 97%

PKA-Dependent and PKA-Independent Pathways for cAMP-Regulated Exocytosis

Seino¹,

Shibasaki²

2005

Physiological Reviews

518

447

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“…However, an increase of granules was reported in hypersecretory melanotrophs. It could be due to mechanisms operating at an early stage of granule formation (Bäck and Soinila, 1994).…”

Section: Introductionmentioning

confidence: 99%

Intergranule Fusion in Rat Pars Intermedia Cells

Cedilnik¹,

Kocmur-Bobanović²,

Zorec

2011

Image Anal Stereol

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Using electron microscopy, we studied the morphology of secretory granules in rat pars intermedia cells. We found figures of apparent intergranule fusion, characterized by a tight association of two granules. The fusion was detected in around 2% of all measured granules, indicating a low occurrence of intergranule fusion. To study whether intergranule fusion affects the distribution of granule diameters a simple probabilistic model was developed. It is based on the theory that larger granules are formed by fusion of two or more spherical granules of fixed size, and that the surface of a newly formed granule is equal to the sum of fused granule membranes. The model accounts for the bias on granule diameter measurements due to sectioning of granules. Although the electron microscopy data strongly indicates the existence of intergranule fusion in rat melanotrophs, this process as modelled in the present work does not contribute to the granule diameter distribution significantly. It is likely that in addition to the fusion of larger granules, other processes, such as fusion of microvesicles, may affect the distribution of granule diameters.

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“…Total RNA was isolated from control neurointermediate lobes (n = 5) and subjected to multiplex RNase protection analysis and quantification with a Phosphorlmager to determine the level of each transcript indicated. After quantification, the molecules of mRNA/cell were calculated using a yield of 5 ig RNA per neurointermediate lobe and published values of 3 x iOmelanotropes/adult male rat neurointermediate lobe (Mains et al, 1987;Back, 1989;Back and Soinila, 1994 opposite effect on levels of each of these transcripts. It is interesting that the data demonstrate coordinate regulation of peptide precursor and some, but not a!…”

Section: Transcript Levels Begin To Change Within a Day Of Drug Treatmentioning

confidence: 99%

“…4, POMC transcripts were '-.~200-fo!dmore prevalent than PC2 and CPH transcripts, and 1,000-fold more prevalent than PAM, PC1, or Cytb561 transcripts. Using our observed recovery of 5 ,ug total RNA per neurointermediate lobe and the literature values for the number of melanotropes per neurointermediate lobe (Mains et al, 1987;Back, 1989;Back and Soinila, 1994), we determined the number of molecules of mRNA/me!anotrope. The number of POMC transcripts per cell is estimated to be 31,000, with less prevalent transcripts such as PC 1 and PAM present in the range of 20-30 mRNA molecules per melanotrope.…”

Section: Transcript Levels Begin To Change Within a Day Of Drug Treatmentioning

confidence: 99%

Dopaminergic Regulation of Secretory Granule‐Associated Proteins in Rat Intermediate Pituitary

Oyarce¹,

Hand²,

Mains³

et al. 1996

Journal of Neurochemistry

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The biosynthesis of peptides requires the synthesis of the prohormone, several biosynthetic processing enzymes, and other granule constituents. We have investigated the regulated expression of proopiomelanocortin (POMC) and five enzymes essential for the processing of POMC to smaller, bloactive peptides in intermediate pituitary melanotropes. Rats were treated with a dopaminergic agonist (bromocriptine) or antagonist (haloperidol) for periods ranging from 1 h to 5 days, followed by analyses of mRNA levels and protein biosynthetic rates. Multiplex RNase protection assays showed that bromocriptine treatment caused a striking decrease in POMC mRNA levels, and significant decreases in mRNA levels for prohormone convertase 2 (PC2), carboxypeptidase H (CPH), and peptidylglycine a-amidating monooxygenase (PAM). Smaller increases in mRNA levels were seen after haloperidol stimulation. Protein biosynthetic rates changed more profoundly than mRNA levels at short drug treatment times, indicating a role for translational effects after treatment with bromocriptine and with haloperidol. The homogeneous population of melanotropes in the intermediate lobe of the pituitary allows a quantitative analysis of transcript levels and biosynthetic rates. POMC mRNA levels are 200-1,000-fold higher than levels of any of the processing enzyme mRNAs, and POMC biosynthetic rates exceed those of PC2, PCi, and PAM by 1,000-10,000-fold. Key Words: Proopiomelanocortin-Prohormone convertase 1 -Prohormone convertase 2-Peptidylglycine a-am idating monooxygenase-Cytochrome b 561 -Translation.

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Regulation of secretory granule formation in chronically hypersecretory melanotrophs in the rat pituitary

Cited by 9 publications

References 37 publications

PKA-Dependent and PKA-Independent Pathways for cAMP-Regulated Exocytosis

PKA-Dependent and PKA-Independent Pathways for cAMP-Regulated Exocytosis

Intergranule Fusion in Rat Pars Intermedia Cells

Dopaminergic Regulation of Secretory Granule‐Associated Proteins in Rat Intermediate Pituitary

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