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Altered expression of agouti-related protein and its colocalization with neuropeptide Y in the arcuate nucleus of the hypothalamus during lactation.
Endocrinology. 1999 Jun; 140(6):2645-50.E

Abstract

During lactation, the levels of neuropeptide Y (NPY), which plays an important role in mediating food intake, are significantly elevated in a number of hypothalamic areas, including the arcuate nucleus (ARH). To identify additional hypothalamic systems that might be important in mediating the increase in food intake and alterations in energy homeostasis during lactation, the present studies examined the expression of agouti-related protein (AGRP), a recently described homologue of the skin agouti protein. AGRP is found in the hypothalamus and has been suggested to play an important role in the regulation of food intake. In the first experiment, animals were studied during diestrus of the estrous cycle, a stage of the cycle when estrogen levels are basal and similar to lactation, or during days 12-13 postpartum. Lactating animals had their litters adjusted to eight pups on day 2 postpartum. Brain tissue sections were used to measure AGRP messenger RNA (mRNA) levels by in situ hybridization. AGRP mRNA signal was found mostly in the ventromedial portion of the ARH, which has been shown to contain a high density of NPY neurons. A significant increase in AGRP mRNA content was observed in the mid- to caudal portion of the ARH of lactating animals compared with diestrous females. No difference was found in the rostral portion of the ARH. In the second experiment, double-label in situ hybridization for AGRP and NPY was performed in lactating animals to determine the extent of colocalization of the two peptides in the ARH, using 35S-labeled and digoxigenin-labeled antisense complementary RNA probes. It was found that almost all of the NPY-positive neurons throughout the ARH also expressed AGRP mRNA signal. Furthermore, AGRP expression was confined almost exclusively to NPY-positive neurons. Thus, the present study showed that during lactation, AGRP gene expression was significantly elevated in a subset of the AGRP neurons in the ARH. The high degree of colocalization of AGRP and NPY, coupled with previous reports from our laboratory demonstrating increased NPY expression in the ARH in response to suckling, suggests that AGRP and NPY are coordinately regulated and may be involved in the increase in food intake during lactation.

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Authors+Show Affiliations

Chen P
Division of Neuroscience, Oregon Regional Primate Research Center, Beaverton 97006, USA.
Li C
No affiliation info available
Haskell-Luevano C
No affiliation info available
Cone RD
No affiliation info available
Smith MS
No affiliation info available

MeSH

Agouti Signaling ProteinAgouti-Related ProteinAnimalsAntisense Elements (Genetics)Arcuate Nucleus of HypothalamusFemaleIntercellular Signaling Peptides and ProteinsLactationNeuropeptide YPregnancyProteinsRNA, MessengerRatsRats, Sprague-Dawley

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10342854

Citation

Chen, P, et al. "Altered Expression of Agouti-related Protein and Its Colocalization With Neuropeptide Y in the Arcuate Nucleus of the Hypothalamus During Lactation." Endocrinology, vol. 140, no. 6, 1999, pp. 2645-50.
Chen P, Li C, Haskell-Luevano C, et al. Altered expression of agouti-related protein and its colocalization with neuropeptide Y in the arcuate nucleus of the hypothalamus during lactation. Endocrinology. 1999;140(6):2645-50.
Chen, P., Li, C., Haskell-Luevano, C., Cone, R. D., & Smith, M. S. (1999). Altered expression of agouti-related protein and its colocalization with neuropeptide Y in the arcuate nucleus of the hypothalamus during lactation. Endocrinology, 140(6), 2645-50.
Chen P, et al. Altered Expression of Agouti-related Protein and Its Colocalization With Neuropeptide Y in the Arcuate Nucleus of the Hypothalamus During Lactation. Endocrinology. 1999;140(6):2645-50. PubMed PMID: 10342854.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Altered expression of agouti-related protein and its colocalization with neuropeptide Y in the arcuate nucleus of the hypothalamus during lactation. AU - Chen,P, AU - Li,C, AU - Haskell-Luevano,C, AU - Cone,R D, AU - Smith,M S, PY - 1999/5/26/pubmed PY - 1999/5/26/medline PY - 1999/5/26/entrez SP - 2645 EP - 50 JF - Endocrinology JO - Endocrinology VL - 140 IS - 6 N2 - During lactation, the levels of neuropeptide Y (NPY), which plays an important role in mediating food intake, are significantly elevated in a number of hypothalamic areas, including the arcuate nucleus (ARH). To identify additional hypothalamic systems that might be important in mediating the increase in food intake and alterations in energy homeostasis during lactation, the present studies examined the expression of agouti-related protein (AGRP), a recently described homologue of the skin agouti protein. AGRP is found in the hypothalamus and has been suggested to play an important role in the regulation of food intake. In the first experiment, animals were studied during diestrus of the estrous cycle, a stage of the cycle when estrogen levels are basal and similar to lactation, or during days 12-13 postpartum. Lactating animals had their litters adjusted to eight pups on day 2 postpartum. Brain tissue sections were used to measure AGRP messenger RNA (mRNA) levels by in situ hybridization. AGRP mRNA signal was found mostly in the ventromedial portion of the ARH, which has been shown to contain a high density of NPY neurons. A significant increase in AGRP mRNA content was observed in the mid- to caudal portion of the ARH of lactating animals compared with diestrous females. No difference was found in the rostral portion of the ARH. In the second experiment, double-label in situ hybridization for AGRP and NPY was performed in lactating animals to determine the extent of colocalization of the two peptides in the ARH, using 35S-labeled and digoxigenin-labeled antisense complementary RNA probes. It was found that almost all of the NPY-positive neurons throughout the ARH also expressed AGRP mRNA signal. Furthermore, AGRP expression was confined almost exclusively to NPY-positive neurons. Thus, the present study showed that during lactation, AGRP gene expression was significantly elevated in a subset of the AGRP neurons in the ARH. The high degree of colocalization of AGRP and NPY, coupled with previous reports from our laboratory demonstrating increased NPY expression in the ARH in response to suckling, suggests that AGRP and NPY are coordinately regulated and may be involved in the increase in food intake during lactation. SN - 0013-7227 UR - https://www.unboundmedicine.com/medline/citation/10342854/Altered_expression_of_agouti_related_protein_and_its_colocalization_with_neuropeptide_Y_in_the_arcuate_nucleus_of_the_hypothalamus_during_lactation_ L2 - https://academic.oup.com/endo/article-lookup/doi/10.1210/endo.140.6.6829 DB - PRIME DP - Unbound Medicine ER -