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Differential regulation of KiSS-1 mRNA expression by sex steroids in the brain of the male mouse.
- Source :
-
Endocrinology [Endocrinology] 2005 Jul; Vol. 146 (7), pp. 2976-84. Date of Electronic Publication: 2005 Apr 14. - Publication Year :
- 2005
-
Abstract
- Kisspeptins are products of the Kiss1 gene, which bind to GPR54, a G protein-coupled receptor. Kisspeptins and GPR54 have been implicated in the neuroendocrine regulation of GnRH secretion. To test the hypothesis that testosterone regulates Kiss1 gene expression, we compared the expression of KiSS-1 mRNA among groups of intact, castrated, and castrated/testosterone (T)-treated male mice. In the arcuate nucleus (Arc), castration resulted in a significant increase in KiSS-1 mRNA, which was completely reversed with T replacement, whereas in the anteroventral periventricular nucleus, the results were the opposite, i.e. castration decreased and T increased KiSS-1 mRNA expression. In the Arc, the effects of T on KiSS-1 mRNA were completely mimicked by estrogen but only partially mimicked by dihydrotestosterone, a nonaromatizable androgen, suggesting that both estrogen receptor (ER) and androgen receptor (AR) play a role in T-mediated regulation of KiSS-1. Studies of the effects of T on KiSS-1 expression in mice with either a deletion of the ERalpha or a hypomorphic allele to the AR revealed that the effects of T are mediated by both ERalpha and AR pathways, which was confirmed by the presence of either ERalpha or AR coexpression in most KiSS-1 neurons in the Arc. These observations suggest that KiSS-1 neurons in the Arc, whose transcriptional activity is inhibited by T, are targets for the negative feedback regulation of GnRH secretion, whereas KiSS-1 neurons in the anteroventral periventricular nucleus, whose activity is stimulated by T, may mediate other T-dependent processes.
- Subjects :
- Animals
Body Weight
Dihydrotestosterone pharmacology
Estradiol pharmacology
Estrogen Receptor alpha deficiency
Estrogen Receptor alpha genetics
Hormones blood
In Situ Hybridization
Kisspeptins
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Orchiectomy
Prosencephalon drug effects
Prosencephalon metabolism
Receptors, Androgen deficiency
Receptors, Androgen genetics
Testosterone pharmacology
Tissue Distribution
Brain metabolism
Proteins genetics
RNA, Messenger metabolism
Testosterone physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0013-7227
- Volume :
- 146
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 15831567
- Full Text :
- https://doi.org/10.1210/en.2005-0323