Dynorphin and GABAA Receptor Signaling Contribute to Progesterone's Inhibition of the LH Surge in Female Mice.
Animals
Bicuculline
/ pharmacology
Dynorphins
/ antagonists & inhibitors
Estradiol
/ pharmacology
Female
GABA Antagonists
/ pharmacology
Hypothalamus
/ cytology
Hypothalamus, Anterior
/ cytology
Kisspeptins
/ metabolism
Luteinizing Hormone
/ metabolism
Mice, Inbred C57BL
Naltrexone
/ analogs & derivatives
Neurons
/ cytology
Organophosphorus Compounds
/ pharmacology
Ovariectomy
Progesterone
/ pharmacology
Receptors, GABA-A
/ metabolism
Signal Transduction
/ drug effects
AVPV
GABA
LH surge
dynorphin
progesterone
Journal
Endocrinology
ISSN: 1945-7170
Titre abrégé: Endocrinology
Pays: United States
ID NLM: 0375040
Informations de publication
Date de publication:
01 05 2020
01 05 2020
Historique:
received:
07
09
2019
accepted:
28
02
2020
pubmed:
18
3
2020
medline:
5
1
2021
entrez:
18
3
2020
Statut:
ppublish
Résumé
Progesterone can block estrogen-induced luteinising hormone (LH) surge secretion and can be used clinically to prevent premature LH surges. The blocking effect of progesterone on the LH surge is mediated through its receptor in the anteroventral periventricular nucleus (AVPV) of the hypothalamus. However, the underlying mechanisms are unclear. The preovulatory LH surge induced by estrogen is preceded by a significant reduction in hypothalamic dynorphin and gamma-aminobutyric acid (GABA) release. To test the detailed roles of dynorphin and GABA in an LH surge blockade by progesterone, ovariectomized and 17β-estradiol capsule-implanted (OVX/E2) mice received simultaneous injections of estradiol benzoate (EB) and progesterone (P) or vehicle for 2 consecutive days. The LH level was monitored from 2:30 pm to 8:30 pm at 30-minute intervals. Progesterone coadministration resulted in the LH surge blockade. A continuous microinfusion of the dynorphin receptor antagonist nor-BNI or GABAA receptor antagonist bicuculline into the AVPV from 3:00 pm to 7:00 pm reversed the progesterone-mediated blockade of the LH surge in 7 of 9 and 6 of 10 mice, respectively. In addition, these LH surges started much earlier than the surge induced by estrogen alone. However, 5 of 7 progesterone-treated mice did not show LH surge secretion after microinfusion with the GABAB receptor antagonist CGP-35348. Additionally, peripheral administration of kisspeptin-54 promotes LH surge-like release in progesterone treated mice. These results demonstrated that the progesterone-mediated suppression of the LH surge is mediated by an increase in dynorphin and GABAA receptor signaling acting though kisspeptin neurons in the AVPV of the hypothalamus in female mice.
Identifiants
pubmed: 32181477
pii: 5808894
doi: 10.1210/endocr/bqaa036
pmc: PMC7153819
pii:
doi:
Substances chimiques
GABA Antagonists
0
Kisspeptins
0
Organophosphorus Compounds
0
Receptors, GABA-A
0
norbinaltorphimine
36OOQ86QM1
Progesterone
4G7DS2Q64Y
Estradiol
4TI98Z838E
Naltrexone
5S6W795CQM
Dynorphins
74913-18-1
CGP 35348
87TI61875H
Luteinizing Hormone
9002-67-9
Bicuculline
Y37615DVKC
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© Endocrine Society 2020.
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