Neuropeptidase activity is down-regulated by estradiol in steroid-sensitive regions of the hypothalamus in female mice.
Thimet oligopeptidase (TOP) and prolyl endopeptidase (PEP) are neuropeptidases involved in the hydrolysis of gonadotropin-releasing hormone, a key component of the hypothalamic-pituitary-gonadal axis. GnRH is regulated in part by feedback from steroid hormones such as estradiol. Previously, we demonstrated that TOP levels are down-regulated by estradiol in reproductively-relevant regions of the female rodent brain. The present study supports these findings by showing that TOP enzyme activity, as well as protein levels, in the ventromedial hypothalamic nucleus of female mice is controlled by estradiol. We further demonstrate that PEP levels in this same brain region are down-regulated by estradiol in parallel with those of TOP. These findings provide evidence that these neuropeptidases are part of the fine control of hormone levels in the HPG axis.
Chemistry Department, Wellesley College, Wellesley, MA, USA.
Lisa A
LA
Bruce
Nicole E
NE
Cyr
Jana W
JW
Qiao
Christa C
CC
Defries
Marc J
MJ
Tetel
Adele J
AJ
Wolfson
D000818:Animals; D015536:Down-Regulation; D004789:Enzyme Activation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D007031:Hypothalamus / Q000201:enzymology*; D008666:Metalloendopeptidases / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D000085822:Prolyl Oligopeptidases; D012697:Serine Endopeptidases / Q000378:metabolism*; D013256:Steroids / Q000378:metabolism; D014697:Ventromedial Hypothalamic Nucleus / Q000201:enzymology*
D013256:Steroids; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D012697:Serine Endopeptidases; D000085822:Prolyl Oligopeptidases; D008666:Metalloendopeptidases; C022510:thimet oligopeptidase