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  Galanin-like peptide (GALP) neurone-specific phosphoinositide 3-kinase signalling regulates GALP mRNA levels in the hypothalamus of males and luteinising hormone levels in both sexes

Aziz, R., Beymer, M., Negron, A. L., Newshan, A., Yu, G. Q., Rosati, B., et al. (2014). Galanin-like peptide (GALP) neurone-specific phosphoinositide 3-kinase signalling regulates GALP mRNA levels in the hypothalamus of males and luteinising hormone levels in both sexes. Journal of Neuroendocrinology, 26(7), 426-438. doi:10.1111/jne.12163.

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Aziz, R., Author
Beymer, M., Author
Negron, A. L., Author
Newshan, A., Author
Yu, G. Q., Author
Rosati, B., Author
McKinnon, D., Author
Fukuda, M., Author
Lin, R. Z., Author
Mayer, Christian1, Author              
Boehm, U., Author
Acosta-Martinez, M., Author
Affiliations:
1University of Saarland, Homburg , ou_persistent22              

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Free keywords: galanin-like peptide luteinising hormone phosphoinositide 3-kinase metabolism hypothalamus energy homeostasis gene-expression food-intake possible link body-weight metabolism rat reproduction leptin mouse Endocrinology & Metabolism Neurosciences & Neurology
 Abstract: Galanin-like peptide (GALP) neurones participate in the metabolic control of reproduction and are targets of insulin and leptin regulation. Phosphoinositide 3-kinase (PI3K) is common to the signalling pathways utilised by both insulin and leptin. Therefore, we investigated whether PI3K signalling in neurones expressing GALP plays a role in the transcriptional regulation of the GALP gene and in the metabolic control of luteinising hormone (LH) release. Accordingly, we deleted PI3K catalytic subunits p110 and p110 via conditional gene targeting (cKO) in mice (GALP-p110/ cKO). To monitor PI3K signalling in GALP neurones, these animals were also crossed with Cre-dependent FoxO1GFP reporter mice. Compared to insulin-infused control animals, the PI3K-Akt-dependent FoxO1GFP nuclear exclusion in GALP neurones was abolished in GALP-p110/ cKO mice. We next used food deprivation to investigate whether the GALP-neurone specific ablation of PI3K activity affected the susceptibility of the gonadotrophic axis to negative energy balance. Treatment did not affect LH levels in either sex. However, a significant genotype effect on LH levels was observed in females. By contrast, no genotype effect on LH levels was observed in males. A sex-specific genotype effect on hypothalamic GALP mRNA was observed, with fed and fasted GALP-p110/ cKO males having lower GALP mRNA expression compared to wild-type fed males. Finally, the effects of gonadectomy and steroid hormone replacement on GALP mRNA levels were investigated. Compared to vehicle-treated mice, steroid hormone replacement reduced mediobasal hypothalamus GALP expression in wild-type and GALP-p110/ cKO animals. In addition, within the castrated and vehicle-treated group and compared to wild-type mice, LH levels were lower in GALP-p110/ cKO males. Double immunofluorescence using GALP-Cre/R26-YFP mice showed androgen and oestrogen receptor co-localisation within GALP neurones. Our data demonstrate that GALP neurones are direct targets of steroid hormones and that PI3K signalling regulates hypothalamic GALP mRNA expression and LH levels in a sex-specific fashion.

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Language(s): eng - English
 Dates: 2014
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: Other: WOS:000338041600002
DOI: 10.1111/jne.12163
ISSN: 0953-8194
 Degree: -

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Title: Journal of Neuroendocrinology
  Other : J. Neuroendocrinol.
Source Genre: Journal
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Publ. Info: Eynsham, Oxon, UK : Oxford University Press
Pages: - Volume / Issue: 26 (7) Sequence Number: - Start / End Page: 426 - 438 Identifier: ISSN: 0953-8194
CoNE: https://pure.mpg.de/cone/journals/resource/954925575990