dc.contributor.author |
Singh-Mallah, Gagandeep |
en |
dc.contributor.author |
McMahon, Christopher D |
en |
dc.contributor.author |
Guan, Jian |
en |
dc.contributor.author |
Singh, Kuljeet |
en |
dc.date.accessioned |
2018-10-16T22:18:50Z |
en |
dc.date.issued |
2017-12 |
en |
dc.identifier.issn |
0021-9541 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/42162 |
en |
dc.description.abstract |
In rodents, post-lactational involution of mammary glands is characterized by the loss of mammary epithelial cells via apoptosis, which is associated with a decline in the expression of insulin-like growth factor-1 (IGF-1). Overexpression of IGF-1 delays involution by inhibiting apoptosis of epithelial cells and preserving the remaining secretory alveoli. Cyclic-glycine-proline (cGP), a metabolite of IGF-1, normalizes IGF-1 function under pathological conditions by regulating the bioavailability of IGF-1. The present study investigated the effect of cGP on the physiological decline in IGF-1 function during post-lactational mammary involution. Rat dams were gavaged with either cGP (3 mg/kg) or saline once per day from post-natal d8-22. Before collecting tissue on post-natal d23, a pair of mammary glands were sealed on d20 (72 hr-engorgement, thus representative of late-involution) and d22 (24 hr-engorgement, thus representative of mid-involution), while the remaining glands were allowed to involute naturally (early-involution). During early-involution, cGP accelerated the loss of mammary cells through apoptosis, resulting in an earlier clearance of intact secretory alveoli compared with the control group. This coincided with an earlier up-regulation of the cell survival factors, Bcl-xl and IGF-1R, in the early-involution cGP glands compared with the control glands. During late-involution, cGP reduced the bioactivity of IGF-1, which was evident through decreased phosphorylation of IGF-1R in the regressed alveoli. Maternal administration of cGP did not alter milk production and composition during early-, peak-, or late-stage of lactation. These data show that cGP accelerates post-lactational involution by promoting apoptosis and the physiological decline in IGF-1 function. |
en |
dc.format.medium |
Print-Electronic |
en |
dc.language |
eng |
en |
dc.relation.ispartofseries |
Journal of cellular physiology |
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dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.subject |
Mammary Glands, Animal |
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dc.subject |
Animals |
en |
dc.subject |
Rats |
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dc.subject |
Rats, Sprague-Dawley |
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dc.subject |
Peptides, Cyclic |
en |
dc.subject |
Insulin-Like Growth Factor I |
en |
dc.subject |
Ki-67 Antigen |
en |
dc.subject |
Cell Proliferation |
en |
dc.subject |
Female |
en |
dc.subject |
Caspase 3 |
en |
dc.title |
Cyclic-glycine-proline accelerates mammary involution by promoting apoptosis and inhibiting IGF-1 function. |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1002/jcp.25782 |
en |
pubs.issue |
12 |
en |
pubs.begin-page |
3369 |
en |
pubs.volume |
232 |
en |
dc.rights.holder |
Copyright: The author |
en |
dc.identifier.pmid |
28063218 |
en |
pubs.end-page |
3383 |
en |
pubs.publication-status |
Published |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Journal Article |
en |
pubs.elements-id |
609127 |
en |
pubs.org-id |
Medical and Health Sciences |
en |
pubs.org-id |
Medical Sciences |
en |
pubs.org-id |
Pharmacology |
en |
dc.identifier.eissn |
1097-4652 |
en |
pubs.record-created-at-source-date |
2017-01-08 |
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pubs.dimensions-id |
28063218 |
en |