Evidence for Independently Regulated Secretory Pathways of Proopiomelano‐cortin‐Related Peptides in the Mouse Pars Intermedia

Leenders, H.J.; Jenks, Bruce G.; Relo, Ana Lucia; Roubos, Eric W.

doi:10.1111/j.1365-2826.1990.tb00448.x

Cited by 1 publication

(1 citation statement)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There is also recent evidence of independent regulation of newly synthesized and mature peptides derived from POMC in cells from the mouse pars intermedia. The peptide composition of the two secretory pathways differs with respect to some of the POMC-derived peptides (Leenders, Jenks, Relo & Roubos, 1990). Morphological and biochemical experiments are currently in progress to elucidate the relative distribution of the two hormones in separate populations of secretory vesicles.…”

Section: Discussionmentioning

confidence: 99%

Biosynthesis of corticotrophin-releasing hormone (CRH) in mouse corticotrophic tumour cells expressing the human proCRH gene: intracellular storage and regulated secretion

Castro

Brooke²,

Bullman³

et al. 1991

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

The mouse corticotrophic tumour cell line AtT-20 naturally synthesizes pro-opiomelanocortin (POMC) which is proteolytically processed to N-POMC(1-76), ACTH, beta-lipotrophin and beta-endorphin. The processed products are stored in secretory vesicles and released upon stimulation with specific secretagogues. AtT-20 cells which have been stably transfected with the human corticotrophin-releasing hormone (CRH) gene store and secrete immunoreactive CRH. The present results demonstrate that the CRH precursor is proteolytically processed in the transfected cells to yield the 41 amino acid neuropeptide CRH(1-41). On stimulation with the secretagogue noradrenaline, CRH(1-41) was released into the medium, while the precursor was not. Whilst treatment of wild-type AtT-20 cells with exogenous CRH(1-41) (1 nM) caused a fourfold stimulation of ACTH release above basal levels, the peptide had no effect on ACTH release from the stably transfected cells R1 and R4. These results suggest that the endogenous CRH produced by the transfected R1 and R4 cells may cause down-regulation of their CRH receptors, and thus exogenous CRH cannot cause further stimulation of ACTH release in these cells. We propose that the CRH precursor is correctly processed in the transfected AtT-20 cells (R1 and R4) and that the foreign prohormone is sorted into the secretory pathway.

show abstract

Section: Discussionmentioning

confidence: 99%