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

Oyarce, Ana María; Hand, T.; Mains, Richard E.; Eipper, Betty A.

doi:10.1046/j.1471-4159.1996.67010229.x

Cited by 39 publications

(28 citation statements)

References 66 publications

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“…Together, these findings may indicate that, in resting conditions, pituitary cells synthesize PAM at a rate that exceeds the needs of the cell, and therefore, its steady state is regulated by degradation. A study from our laboratory established that long term stimulation of exocytosis results in up-regulation of mRNA and protein the levels of pro-hormone and processing enzymes (36). Our present results suggest the interesting possibility that sustained exocytotic stimulation (like the one produced by the Ba 2ϩ /PMA paradigm) might regulate PAM protein levels post-translationally diverting newly synthesized enzyme molecules from a degradative pathway.…”

Section: Discussionmentioning

confidence: 53%

Retrieval and Reuse of Pituitary Secretory GranuleProteins

Ferraro

Eipper

Mains

2005

Journal of Biological Chemistry

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The pituitary contains professional secretory cells, devoting a large fraction of their energy to the synthesis of hormones that are stored for secretion in response to a complex mixture of inputs. Ba 2؉ , a substitute for Ca 2؉ , and phorbol ester, a mimic for diacylglycerol, have a synergistic effect on exocytosis. By using these secretagogues, we developed a paradigm in which phorbol ester potentiation of Ba 2؉ -evoked exocytosis produces a robust secretory response in multiple pituitary cell types. Because cells subjected to this stimulatory paradigm remain healthy despite their greatly reduced hormone content, we used this paradigm to study the fate of granule membrane proteins. We examined the turnover of peptidylglycine ␣-amidating monooxygenase (PAM), a membrane enzyme involved in the final maturation of many peptides, and VAMP2, a vesicle soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE). The stability of recently synthesized PAM was increased by sustained exocytosis. Biotinylation studies established that the appearance of integral membrane PAM at the plasma membrane was stimulated along with hormone secretion. PAM biotinylated on the cell surface undergoes cleavage to yield soluble peptidylglycine-␣-hydroxylating monooxygenase that can then be secreted in a regulated fashion. Consistent with a kissand-run or cavicapture mode of secretion (Taraska,

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Section: Discussionmentioning

confidence: 53%

Retrieval and Reuse of Pituitary Secretory GranuleProteins

Ferraro

Eipper

Mains

2005

Journal of Biological Chemistry

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“…To confirm the role of dopaminergic pathways in the control of intermediate lobe ACTH release, 7B2 null and WT mice received daily injections of bromocriptine, a dopaminergic agonist (34). The levels of circulating ACTH in each of the two 7B2 nulls were reduced by 46 and 51%, respectively, after one injection, and by 75 and 60% after three injections; levels of ACTH in the WT controls did not decrease.…”

Section: In Situ Hybridization Of Pomc Mrna Indicates That Pomc Produmentioning

confidence: 99%

Mortality in 7B2 null mice can be rescued by adrenalectomy: Involvement of dopamine in ACTH hypersecretion

Laurent

Kimble

Peng

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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(1999) Cell 96, 689). Here, we have compared the 7B2 and PC2 null mouse models to determine why the 7B2 null, but not the PC2 null, exhibits a lethal disease state. Both 7B2 and PC2 nulls contained highly elevated pituitary adrenocorticotropic hormone (ACTH); the neurointermediate lobe content of ACTH in 7B2 nulls was 13-fold higher than in WT mice; that of the PC2 null was 65-fold higher. However, circulating ACTH levels were much higher in the 7B2 null than in the PC2 null. Because hypothalamic inhibitory dopaminergic control represents the major influence on intermediate lobe proopiomelanocortin-derived peptide secretion, dopamine levels were measured, and they revealed that 7B2 null pituitaries contained only one-fourth of WT pituitary dopamine. Adrenalectomized 7B2 null animals survived past the usual time of death at 5 weeks; a month after adrenalectomy, they exhibited normal levels of pituitary dopamine, circulating ACTH, and corticosterone. Elevated corticosterone, therefore, seems to play a central role in the lethal phenotype of the 7B2 null, whereas a 7B2-mediated dopaminergic deficiency state may be involved in the actual ACTH hypersecretion phenomenon. Interestingly, adrenalectomized 7B2 nulls also developed unexpectedly severe obesity.

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“…Since peptide amidation is a rate limiting step in the biosynthesis of NPY and many other neuropeptides, we monitored peptidylglycine ␣ -amidating monooxygenase (PAM), the only enzyme that catalyzes this modification (Prigge et al 2000). POMC biosynthesis in melanotropes responds to dopaminergic drugs, and changes in PAM parallel POMC (Oyarce et al 1996). Earlier studies demonstrated changes in PAM and prohormone convertase 2 mRNA levels in response to acute ECS (Bhat et al 1993).…”

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confidence: 99%