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EP24.15 as a Potential Regulator of Kisspeptin Within the Neuroendocrine Hypothalamus
- Source :
- Endocrinology. 157:820-830
- Publication Year :
- 2015
- Publisher :
- The Endocrine Society, 2015.
-
Abstract
- The neuropeptide kisspeptin (Kiss1) is integral to the advent of puberty and the generation of cyclical LH surges. Although many complex actions of Kiss1 are known, the mechanisms governing the processing/regulation of this peptide have not been unveiled. The metallo enzyme, endopeptidase 24.15 (thimet oligopeptidase), has been demonstrated to play a key role in the processing and thus the duration of action of the reproductive neuropeptide, GnRH, which signals downstream of Kiss1. Initial in silico modeling implied that Kiss1 could also be a putative substrate for EP24.15. Coincubation of Kiss1 and EP24.15 demonstrated multiple cleavages of the peptide predominantly between Arg29-Gly30 and Ser47-Phe48 (corresponding to Ser5-Phe6 in Kiss-10; Kiss-10 as a substrate had an additional cleavage between Phe6-Gly7) as determined by mass spectrometry. Vmax for the reaction was 2.37±0.09 pmol/min · ng with a Km of 19.68 ± 2.53μM, which is comparable with other known substrates of EP24.15. EP24.15 immunoreactivity, as previously demonstrated, is distributed in cell bodies, nuclei, and processes throughout the hypothalamus. Kiss1 immunoreactivity is localized primarily to cell bodies and fibers within the mediobasal and anteroventral-periventricular hypothalamus. Double-label immunohistochemistry indicated coexpression of EP24.15 and Kiss1, implicating that the regulation of Kiss1 by EP24.15 could occur in vivo. Further studies will be directed at determining the precise temporal sequence of EP24.15 effects on Kiss1 as it relates to the control of reproductive hormone secretion and treatment of fertility issues.
- Subjects :
- Male
0301 basic medicine
medicine.medical_specialty
education
Hypothalamus
Neuropeptide
Gonadotropin-releasing hormone
Metestrus
Biology
Mass Spectrometry
Gonadotropin-Releasing Hormone
03 medical and health sciences
Endocrinology
Kisspeptin
Internal medicine
Escherichia coli
medicine
Animals
Computer Simulation
Secretion
Original Research
Kisspeptins
Thimet oligopeptidase
Metalloendopeptidases
Immunohistochemistry
Endopeptidase
Rats
030104 developmental biology
Female
Proestrus
Cytokinesis
Subjects
Details
- ISSN :
- 19457170 and 00137227
- Volume :
- 157
- Database :
- OpenAIRE
- Journal :
- Endocrinology
- Accession number :
- edsair.doi.dedup.....81f16b2485d9d9eae48ee4e77c854f49