PMID- 28384629
OWN - NLM
STAT- MEDLINE
DCOM- 20190107
LR  - 20240315
IS  - 1423-0194 (Electronic)
IS  - 0028-3835 (Print)
IS  - 0028-3835 (Linking)
VI  - 106
IP  - 2
DP  - 2018
TI  - Estrogen and Progesterone Integration in an in vitro Model of RP3V Kisspeptin 
      Neurons.
PG  - 101-115
LID - 10.1159/000471878 [doi]
AB  - Positive feedback on gonadotropin release requires not only estrogen but also 
      progesterone to activate neural circuits. In rodents, ovarian estradiol (E2) 
      stimulates progesterone synthesis in hypothalamic astrocytes (neuroP), needed for 
      the luteinizing hormone (LH) surge. Kisspeptin (kiss) neurons are the principal 
      stimulators of gonadotropin-releasing hormone neurons, and disruption of kiss 
      signaling abrogates the LH surge. Similarly, blocking steroid synthesis in the 
      hypothalamus or deleting classical progesterone receptor (PGR) selectively in 
      kiss neurons prevents the LH surge. These results suggest a synergistic action of 
      E2 and progesterone in kiss neurons to affect gonadotropin release. The mHypoA51, 
      immortalized kiss-expressing neuronal cell line derived from adult female mice, 
      is a tractable model for examining integration of steroid signaling underlying 
      estrogen positive feedback. Here, we report that kiss neurons in vitro integrate 
      E2 and progesterone signaling to increase levels of kiss translation and release. 
      mHypoA51 neurons expressed nonclassical membrane progesterone receptors (mPRalpha and 
      mPRbeta) and E2-inducible PGR, required for progesterone-augmentation of E2-induced 
      kiss expression. With astrocyte-conditioned media or in mHypoA51-astrocyte 
      co-culture, neuroP augmented stimulatory effects of E2 on kiss protein. 
      Progesterone activation of classical, membrane-localized PGR led to activation of 
      MAPK and Src kinases. Importantly, progesterone or Src activation induced release 
      of kiss from E2-primed mHypoA51 neurons. Consistent with previous studies, the 
      present results provide compelling evidence that the interaction of E2 and 
      progesterone stimulates kiss expression and release. Further, these results 
      demonstrate a mechanism though which peripheral E2 may prime kiss neurons to 
      respond to neuroP, mediating estrogen positive feedback.
CI  - (c) 2017 S. Karger AG, Basel.
FAU - Mittelman-Smith, Melinda A
AU  - Mittelman-Smith MA
FAU - Wong, Angela M
AU  - Wong AM
FAU - Micevych, Paul E
AU  - Micevych PE
LA  - eng
GR  - R01 HD042635/HD/NICHD NIH HHS/United States
PT  - Journal Article
DEP - 20170407
PL  - Switzerland
TA  - Neuroendocrinology
JT  - Neuroendocrinology
JID - 0035665
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (Estrogens)
RN  - 0 (Kisspeptins)
RN  - 0 (Receptors, Progesterone)
RN  - 4G7DS2Q64Y (Progesterone)
RN  - EC 2.7.10.2 (src-Family Kinases)
RN  - EC 2.7.11.24 (Mapk1 protein, mouse)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
SB  - IM
EIN - Neuroendocrinology. 2018;106(2):115. PMID: 29439262
MH  - Animals
MH  - Astrocytes/metabolism
MH  - Cell Line
MH  - Coculture Techniques
MH  - Culture Media, Conditioned
MH  - Estrogen Receptor alpha/metabolism
MH  - Estrogens/administration & dosage/*metabolism
MH  - Feedback, Physiological/physiology
MH  - Female
MH  - Hypothalamus/drug effects/metabolism
MH  - Kisspeptins/*metabolism
MH  - Mice
MH  - Mitogen-Activated Protein Kinase 1/metabolism
MH  - Mitogen-Activated Protein Kinase 3/metabolism
MH  - Neurons/drug effects/*metabolism
MH  - Progesterone/administration & dosage/*metabolism
MH  - Protein Biosynthesis/physiology
MH  - Receptors, Progesterone/metabolism
MH  - src-Family Kinases/metabolism
PMC - PMC5750133
MID - NIHMS919190
OTO - NOTNLM
OT  - ERalpha
OT  - Estrogen positive feedback
OT  - MAPK
OT  - Progesterone receptor
OT  - Src
OT  - mPR
EDAT- 2017/04/07 06:00
MHDA- 2019/01/08 06:00
PMCR- 2019/01/01
CRDT- 2017/04/07 06:00
PHST- 2016/12/05 00:00 [received]
PHST- 2017/03/21 00:00 [accepted]
PHST- 2017/04/07 06:00 [pubmed]
PHST- 2019/01/08 06:00 [medline]
PHST- 2017/04/07 06:00 [entrez]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 000471878 [pii]
AID - 10.1159/000471878 [doi]
PST - ppublish
SO  - Neuroendocrinology. 2018;106(2):101-115. doi: 10.1159/000471878. Epub 2017 Apr 7.